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Abstract

Objective:

To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS).

Methods:

We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed.

Results:

We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 × 10−6, including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA.

Conclusions:

We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps.
Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder of unknown cause. Clinical features include parkinsonism, cerebellar ataxia, pyramidal signs, and dysautonomia. MSA typically presents as a sporadic disease, although rare reports of familial occurrences have been described,13 and there is a greater risk of parkinsonian disorders in relatives of patients with MSA.4
The pathogenesis of MSA is largely unknown. Identification of α-synuclein-positive glial cytoplasmic inclusions as a neuropathologic hallmark provided the first clue that abnormal protein accumulation is involved in the development of MSA.5 Furthermore, it suggested a link to other neurodegenerative diseases that are characterized by α-synuclein deposition, commonly referred to as synucleinopathies. These include Parkinson disease (PD), MSA, dementia with Lewy bodies, pure autonomic failure, and neurodegeneration with brain iron accumulation type I.6
Additional evidence in support of shared pathogenic mechanisms among synucleinopathies was suggested by recent genetic findings demonstrating that variants at the SNCA locus, coding for the deposited α-synuclein protein, are associated with increased risk for PD and MSA.7,8 In addition, the (MAPT) H1 haplotype has been associated with MSA.7,9 More recently, the COQ2 gene was reported to harbor mutations in familial MSA cases from Japan.10 However, follow-up studies in non-Asian ethnic cohorts were unable to replicate this finding.11,12 Thus, many prior observations require further evaluation.
To investigate whether common genetic risk factors play a role in MSA, we performed a genome-wide association study (GWAS) including 918 patients with MSA and 3,864 controls.

METHODS

Study design.

We performed a multicenter GWAS with patients with MSA of European ancestry and regionally matched controls. Collection sites for this study included brain banks and clinical centers in Germany, Austria, Netherlands, Denmark, the United Kingdom, Italy, Portugal, Spain, and the United States (table e-1 at Neurology.org). Since patients were recruited in different geographic regions across Europe and the United States, we matched cases with regional controls. Genotype data of healthy individuals from previous GWAS were obtained from Germany, the United Kingdom, the United States, and Italy. The MSA cases were grouped into 4 geographic regions and each case was matched with 4 controls from the same geographic region: UK and Irish MSA cases were matched with UK controls; Northern European MSA cases from Germany, Netherlands, Belgium, Austria, Denmark, and Sweden were matched with German controls; Southern European cases from Italy and Spain were matched with Italian controls; American MSA cases were matched with American controls. Matching was carried out using multidimensional scaling based on the first 2-component vectors for each subpopulation, derived from common variants assayed in both cases and controls (minor allele frequency [MAF] > 0.05). A flowchart of studied populations and quality control steps is shown in figure e-1.

Study participants.

DNA samples from a total of 1,030 patients with MSA were collected for this study (details for each population are shown in table 1, demographics are listed in table e-2). Patients were clinically diagnosed with possible or probable MSA (n = 699) by movement disorders specialists, or pathologically with definite MSA (n = 331) by neuropathologists according to Gilman criteria.13 For controls, we used genotype data from 3,864 previously published neurologically normal individuals from the United Kingdom (n = 936 samples), Germany (n = 944 samples), United States (n = 794 samples), and Italy (n = 1,190 samples) (table 1). All controls were genotyped on Illumina BeadChips (Illumina, San Diego, CA, USA). Details about sample collection and genotyping procedures in control cohorts have been described elsewhere.7,1416
Table 1 Samples included

Standard protocol approvals, registrations, and patient consents.

The appropriate institutional review boards approved the study, and written informed consent was obtained for each participant.

Genotyping.

Samples from 1,030 MSA cases were genotyped on 1 of 3 Illumina genotyping BeadChips (Human610-Quad v1, Human660W-Quad v1, or HumanOmniExpress-12 v1). Control samples were genotyped on the following BeadChips: UK WTCCC on Illumina Human1.2M-DuoCustom BeadChip; US, German, and Italian controls on Illumina BeadChips 550K version 1 chips or version 3.7,14,16 These chip versions have 343,783 unique single nucleotide polymorphisms (SNPs) in common, and only shared SNPs were used for downstream analyses.

Statistical analysis.

Genotype calling.

For each of the 3 genotyping platforms, raw data were imported to GenomeStudio (v2010.1, genotyping module v1.6.3, Illumina) and genotype calls were reclustered using a no-call threshold of <0.15.

Quality control.

For quality control, we excluded samples with a genotyping call rate <95%, duplicate samples, cryptically related individuals (pi-hat threshold >0.2), individuals in whom the reported sex did not match the genotypic sex, and individuals with non-European ancestry as determined by multiple dimensional scaling analysis (samples deviating >6 SDs from the CEU/TSI population were excluded; see figure e-2). Next, we excluded SNPs with inaccurate cluster separation (cluster separation score <0.3), SNPs that were not shared among all 3 genotyping chip versions, and SNPs with an individual SNP call rate <95%. Following this step, we excluded SNPs with missingness by haplotype or phenotype that exceeded a significance of p value < 0.0001 or a significant deviation from Hardy-Weinberg equilibrium with a p value < 0.00001. Of the remaining SNPs, only those with a MAF >0.01 were used for downstream analyses.

Power calculations and heritability analysis.

Power calculations were performed for a GWAS testing 918 cases and 3,864 controls under a log-additive and a recessive model (QUANTO software v1.2.3). A minor allele frequency >1% and a 2-sided α = 5 × 10−8 were assumed. Under the log-additive model (figure e-3A), power analysis for this study indicated greater than 80% power to detect associated loci with an odds ratio greater than 1.8 at risk allele frequencies between 7% and 87%. We recently also performed a heritability analysis based on our GWAS data demonstrating that the heritability for MSA due to common coding variants is estimated to be between 2.1% and 6.7%.17

Genotype imputation.

About 4,903,804 SNPs were imputed based on haplotype reference data from the 1000 Genomes project (1000genomes.org/; December 2010 version). These data were derived from studying the genomic sequence of 104 participants of European ancestry. Imputations were performed for each of the 4 cohorts separately using MACH software as described elsewhere (version 1.0.16).18,19 SNPs with an R2 <0.3 and MAF <0.01 were excluded from further analysis as imputed genotypes below this threshold are likely to be of poor quality.

Association tests.

Due to the relatively diverse ancestries of European and US cohorts included in this study, we used principal component vectors 1 to 10 from a multidimensional scaling analysis generated in PLINK as covariates to adjust for possible population substructure in the logistic regression model used for the GWAS (figure e-4). The genomic inflation factor was λ = 1.057. For each SNP, p values and odds ratios under the additive models were calculated using Mach2dat software.18,19 Only SNPs exceeding the conservative Bonferroni threshold for multiple testing (p < 5 × 10−8) were considered genome-wide significant. We also performed a subanalysis for association in pathologically confirmed MSA cases (n = 295 cases after quality control) vs 3,864 controls. The genomic inflation factor in this subgroup was λ = 1.024.

SNCA SNP genotyping using a restriction enzyme assay.

SNP rs11931074, located downstream of the SNCA gene, was regenotyped using a restriction enzyme assay. Primers were designed to amplify the SNP and surrounding region. Restriction enzyme Bsr1 (New England Biolabs, Ipswich, MA) was used to cut the PCR product. The major allele was cut, whereas the minor allele remained uncut. Disease association was tested with a χ2 test.

Analysis of brain tissue quantitative trait loci.

For SNPs of interest, we attempted to infer functional consequences in frontal cortex and cerebellar tissue samples from neurologically normal individuals that were assayed for both genome-wide methylation and expression levels.20 These analyses may shed light on potential disease mechanisms for follow-up in future studies. We tested cis associations (any methylation or expression probes ±1 Mb from each SNP) in each of the datasets.21

RESULTS

Genotyping, imputation, and quality control.

After quality control procedures, the total study consisted of 918 cases and 3,864 controls. Of the MSA cases, 291 had a pathologically confirmed diagnosis. Samples were successfully genotyped for 267,998 SNPs and imputed to 4,903,804 SNPs. After removal of extreme ancestry outliers and using multidimensional scaling component vectors as covariates in regression models, only mild population stratification was evident based on genomic inflation factor calculations (λ = 1.057) (figure e-2).

Association results.

Statistical analysis of association under an additive model was performed in the full case-control dataset (figure 1) and in the subset of MSA cases with neuropathologically confirmed diagnosis. Loci with the lowest p values (<1 × 10−6) in the full dataset and pathology confirmed cases are shown in tables 2 and e-3, respectively. In the full dataset, we identified 4 loci for future follow-up in a larger sample series at a p value <1 × 10−7 including the genes FBXO47, ELOVL7, EDN1, and MAPT. None of the tested SNPs surpassed the Bonferroni threshold for multiple testing (p value < 5 × 10−8) in the full dataset or in the subanalysis of pathologically confirmed cases.
Figure 1 Manhattan plot showing association results in multiple system atrophy
p Values under the additive association model are log transformed (y-axis) and plotted against the chromosomal position (x-axis). The dotted line indicates the threshold of potentially interesting single nucleotide polymorphisms.
Table 2 Summary of loci with a p value below 1E-6

COQ2 in the MSA GWAS data.

Recently, homozygous (or compound heterozygous) mutations in COQ2 were reported in familial cases of MSA in Japan.10 While coding variants were also found at a higher frequency in sporadic MSA compared to controls, this finding did not replicate outside of Japanese MSA samples. We investigated the COQ2 locus for common variation in our GWAS data. A total of 453 SNPs in the COQ2 gene and the flanking region ±100 kb (build 36.3 positions) were tested for association. The most associated SNP was chr4:84473327 with a p value of 0.02169, which is far from genome-wide or even regional Bonferroni-adjusted significance. We therefore lack evidence that common genetic variation in the COQ2 locus plays a major role in MSA risk in the European/Northern American population.

SNCA rs11931074 SNP genotyping.

SNP rs11931074 in the SNCA locus (or rs3822086, which is in close linkage disequilibrium) has been linked to MSA in several smaller studies.8,22,23 This SNP is not represented on the OmniExpress Bead arrays; hence, it was not genotyped in any samples run on this array (n = 703) and consequently was not in the dataset of genotyped SNPs in common. Instead, the allele frequency was calculated postimputation, demonstrating that it was neither significantly associated in the entire dataset (p value = 0.4722) nor in the subgroup of definite MSA cases (p value = 0.4407). We decided to regenotype SNP rs11931074 in the MSA GWAS cohort using a restriction enzyme to exclude technical or imputation uncertainty (despite a high imputation score of 0.9670). Within the GWAS cohort, 906 MSA samples were available for regenotyping (table 3). In controls, data for this SNP were available from the bead array data. The minor allele of SNP rs11931074 was slightly more common in MSA cases vs controls (8.3% vs 7.3%) but again no significant association was found with MSA (χ2 = 2.6; p value = 0.27). This is in concordance with the imputed GWAS finding, but contradicts previous reports in the literature.8,22,23
Table 3 Results from the SNCA SNP rs11931074 restriction enzyme assay

Analysis of brain tissue quantitative trait loci in candidate loci.

Twenty-one out of 24 SNPs of interest (p value < 1 × 10−5) passed quality control in the mRNA expression datasets, and 23 SNPs of interest passed quality control in the CpG methylation datasets. We tested multiple probes per SNP in each set of analyses. A total of 168 unique SNP–probe pairs were tested in the frontal cortex mRNA expression dataset, 165 pairs in the cerebellar mRNA expression dataset, and 391 pairs in the frontal cortex and cerebellar CpG methylation dataset. Associations were tested using linear regression adjusting for appropriate covariates and resulting p values were adjusted based on the false-discovery rate correction as previously described.21
After correcting for multiple testing, we found 8 significant associations between SNPs of interest and either CpG methylation or mRNA expression (table e-4). All of these were located on chromosome 17 and associated with 3 SNPs (rs78523330, rs9303521, and rs916888) in a region spanning 8 MB. SNP rs9393521 is located only 174 Kb upstream of MAPT, a gene previously suggested as a risk gene for MSA, and it is within a large 900 kb inversion polymorphism surrounding the MAPT locus.

DISCUSSION

The contribution of common genetic factors to disease development has been established for many neurodegenerative conditions, which are complex, often sporadic conditions such as PD and progressive supranuclear palsy. In MSA, the identity of these contributing genetic factors remains almost entirely unknown. Here, we describe a GWAS investigating common genetic markers in 918 MSA cases and 3,864 controls for disease association.
Although none of the tested SNPs surpassed the stringent Bonferroni threshold, we identified 4 MSA regions with p values <1 × 10−6: FBXO47, ELOVL7, EDN1, and MAPT. These loci are most promising for further follow-up.
Among the most highly associated regions is the MAPT locus. MAPT is an intriguing candidate as it has already been implicated in a number of neurodegenerative diseases, particularly in tauopathies such as progressive supranuclear palsy, frontotemporal degeneration, and Alzheimer dementia.24,25 Although tau is not considered a key protein in MSA neuropathology, PD—which is also an α-synucleinopathy—has been found to be consistently associated with common variation in the MAPT locus.7 Furthermore, MSA was also previously found to be associated with the MAPT H1 haplotype in a small cohort of American MSA cases.9 These results, however, will need to be verified in a larger MSA cohort.
Located on chromosome 6, EDN1 is part of the endothelin gene family, which functions in the maintenance of vascular tone. Studies have demonstrated the presence of endothelin peptides in nonvascular structures including epithelial cells, glia, and neurons.26,27 Given the phenotype of autonomic dysfunction or failure in patients with MSA, one may hypothesize that such pathophysiology may be associated with variation in EDN1.
ELOVL7, originating on chromosome 5, is involved in transferase activity. Chiefly, transferase is a condensing enzyme that acts as a catalyst for the synthesis of saturated and polyunsaturated very long chain fatty acids.28,29
FBXO47 has a known association with papillary renal cell carcinoma.30 Located on chromosome 17, FBXO47 promotes protein ubiquitination and degradation via phosphorylation, which are critical mechanisms in many neurodegenerative diseases.30,31 This locus could provide an important mechanism to MSA pathology in light of the oligodendroglial α-synuclein burden, but requires further study to draw any conclusions.
Common variation in the COQ2 gene (recently found to be mutated in familial and sporadic probable MSA cases in Japan) did not show a significant association in the MSA GWAS data. This suggests that common genetic variation in this gene does not play a major role in disease pathogenesis in patients with MSA of European descent.
We were unable to replicate the previously reported association of variants at the SNCA.8,22,23 A Korean study was also unable to reproduce the association indicating possible differences between populations or an actual null result.32 The previously associated SNP rs11931074 has considerable variation in frequency among different populations. The reported risk allele has a frequency of about 7%–8% in our different European controls and in the European HapMap data.33 In contrast, the same allele is much more abundant in Asian and African populations (e.g., 58% in Japanese and 68% in Yorubans). Our study attempts to account for both interpopulation and intrapopulation heterogeneity through principal component analysis, and interpopulation heterogeneity of SNCA is a plausible explanation for the previous findings.
The quantitative trait analysis data suggest a complex risk locus on chromosome 17. This includes several SNPs in the region associated with multiple expression or methylation effects. Several of these genes are involved in pathways potentially relevant to MSA pathology: namely, the ribosylation protein (ARL17A), the ribosome protein (RPL19), and the proteasome protein (PSMB3).
The disease pathology of several neurodegenerative disorders illustrates a common theme of disrupted proteasomal protein clearance and degradation. Notably, PSMB3 may be involved in trinucleotide repeat expansion—a phenomenon seen in several hereditary neurologic disorders (in particular autosomal dominant ataxias)—and it may be driving the trinucleotide expansion process.34 Supporting this hypothesis, there is considerable clinical overlap between MSA and several hereditary ataxias.35,36 Similarly, ribosomal dysfunction with aberrant protein synthesis may promote neurodegeneration.37 Interestingly, no alteration in expression of MAPT—the most obvious candidate gene in the chromosome 17 locus—was found. All but one associated QTL in MSA were found in cerebellar tissue (table e-4). Since the cerebellum is among the most disturbed brain regions in MSA, differences in expression in this region are consistent with an etiologic role in MSA.
There are a number of limitations to this study. First, although this represents by far the largest collection of MSA samples to date, the number of MSA cases is still relatively small for a GWAS. GWAS are designed to identify disease variants of relatively high frequency (MAF >1%) in a population operating under the common disease/common variant hypothesis.38 In PD, most identified risk factors have an odds ratio (OR) between 0.8 and 1.5.39 Similarly, in Alzheimer disease—apart from APOE (OR ∼4)—common genetic risk factors have low ORs ranging from 0.8 to 1.2. In these diseases, successful identification of significant loci was only feasible with considerably larger sample sizes than our study. However, with our current number we can reasonably exclude the existence of common risk alleles of large effect. A second limitation is the use of population control cohorts rather than age-matched controls, which increases the chance for population heterogeneity. We applied stringent corrections, including principal components from multidimensional scaling as covariates in our statistical model to address this concern. Third, the misdiagnosis rate of clinically ascertained patients, in particular those in early disease stages, can be as high as 38%.40 We addressed this concern by including a large number of pathology-proven cases (∼ one-third of all patients in this study). The inclusion of pathology-confirmed cases is particularly important for future follow-up studies in MSA.
Finally, a major challenge is that currently no additional large cohorts of MSA cases with a similar genetic background are available. A comparison of European and non-European cohorts may be informative with regard to interpopulation heterogeneity.
None of the studied variants were statistically significant after appropriate correction for multiple testing. However, we identified 4 promising loci that could reveal important insight into the disease pathways of MSA. Increasing the sample size of our GWAS will be key to the successful confirmation of these candidate loci and the identification of other risk genes.

GLOSSARY

GWAS
genome-wide association study
MAF
minor allele frequency
MSA
multiple system atrophy
OR
odds ratio
PD
Parkinson disease
SNP
single nucleotide polymorphism

ACKNOWLEDGMENT

DNA and brain samples: The authors used DNA samples and phenotype data from the NINDS Human Genetics Resource Center DNA and Cell Line Repository at Coriell (Newark, NJ; ccr.coriell.org/ninds), and thank the patients and the submitters who contributed samples to this repository. Human tissue was obtained from the Queen Square Brain Bank (London, UK), the Institute of Psychiatry Brain Bank, King's College (London, UK), the UK Parkinson's disease tissue bank at Imperial College (London, UK), Newcastle Brain Tissue Resource at Newcastle University (Newcastle, UK), the Manchester Brain Bank at the University of Manchester (Manchester, UK), Jacksonville Brain Bank for Alzheimer's, Parkinson's and Related Disorders at the Mayo Clinic (Jacksonville, FL), the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland (Baltimore, MD), the New York Brain Bank of the Taub Institute at Columbia University (New York, NY), the Human Brain and Spinal Fluid Resource Center (Los Angeles, CA), the Miami Brain Bank (Miami, FL), the Center for Neurodegenerative Disease Research at the University of Pennsylvania (Philadelphia, PA), the Harvard Brain Bank (Boston, MA), the Emory University Alzheimer's Disease Research Center Brain Bank (Atlanta, GA), Neurobiobank München at the Ludwig-Maximilians-Universität (Munich, Germany), Brain Bank Center Würzburg (Würzburg, Germany), the Netherlands Brain Bank at the Netherlands Institute for Neuroscience (Amsterdam, Netherlands), and the Neurological Tissue Bank at the University of Barcelona (Barcelona, Spain). The Italian samples were obtained from the Parkinson Institute Biobank (parkinsonbiobank.com), member of the Telethon Network of Genetic Biobank (project n. GTB12001) funded by TELETHON Italy, and supported by “Fondazione Grigioni per il Morbo di Parkinson.”

Data Supplement

Neurology® data supplements are not copyedited before publication. Published editorials and translations have been copyedited. © 2016 American Academy of Neurology. Files in this Data Supplement:

Footnote

Supplementary Material

File (1530.pdf)
File (pellecchia_coinvestigators.docx)
File (supplemental_material.pdf)

AUTHOR AFFILIATIONS

From the Departments of Molecular Neuroscience and Movement Disorders and The Reta Lila Weston Institute (A.S., A.L., K.M., N.E.M., L.S., V.C., H.L., S.S.O., N.W.W., J.A.H., T.R., J.L.H., H.H.), Department of Clinical Neuroscience (H.R.M.), and Sobell Department of Motor Neuroscience and Movement Disorders (N.Q., K.P.B.), UCL Institute of Neurology, London, UK; Klinik für Neurologie (A.S.), Universitätsklinik der Johann-Wolfgang-Goethe Universität Frankfurt, Germany; Laboratory of Neurogenetics, National Institute on Aging (S.W.S., M.A.N., M.F., T.R.P., B.J.T., A.B.S.), and Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke (S.W.S.), National Institutes of Health, Bethesda, MD; Department of Neuroscience (S.W.S.), Georgetown University, Washington, DC; Department of Neurology (S.W.S.), Johns Hopkins Hospital, Baltimore, MD; Department of Neurodegenerative Diseases (C.S., T.G.), Hertie Institute for Clinical Brain Research, and German Center for Neurodegenerative diseases (DZNE), Tübingen, Germany; Department of Neuroscience (O.A.R., D.W.D.), Mayo Clinic, Jacksonville, FL; Division of Life Science (K.M.), Hong Kong University of Science and Technology, Hong Kong SAR, China; National Institute on Aging (L.F.), National Institutes of Health, Baltimore, MD; Department of Neuroscience (H.J.F., T.R.M.), Georgetown University, Washington, DC; Department of Neurology (G.D.), UKSH, Kiel Campus, Christian-Albrechts University Kiel, Germany; Division of Neurology (H.W.), Department of Clinical Sciences, University Hospital, Lund, Sweden; Istituto Clinico Humanitas (A.A.), Università Cattolica del Sacro Cuore, Milan, Italy; Service of Neurology (J.I.), University Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria (UC), Santander, Spain; Institute of Neurology (W.P., G.K.W.), Medical University Innsbruck, Austria; Centre of Nervous Diseases (W.O.), Philipps-University of Marburg; Department of Neurology (G.U.H.), Technische Universität München; German Center for Neurodegenerative Diseases (DZNE) (G.U.H.), Munich; Department of Neurology (U.W.) and German Center for Neurodegenerative Diseases (U.W.), University Hospital of Bonn Medical Center, Germany; Parkinson Institute (S.G.), Istituti Clinici di Perfezionamento, Milan; Center for Neurodegenerative Diseases (M.T.P.), Department of Medicine and Surgery, Neuroscience Section, University of Salerno, Italy; Clinical Pharmacological Unit (J.F.), Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Portugal; Hospital Clinic (E.T.), University of Barcelona, Spain; Department of Neurology (B.R.B.), Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands; Clinical Investigation Center CIC1436 (O.R.), Departments of Clinical Pharmacology and Neurosciences, INSERM and University Hospital of Toulouse, Faculty of Medicine; Centre de Référence Atrophie Multisystématisée (W.G.M.), CHU de Bordeaux, Pessac; and Université de Bordeaux (W.G.M.), Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.

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Letters to the Editor
29 December 2016
COQ2 variants and risk for multiple system atrophy
Sonja W. Scholz, Assistant Clinical Investigator
Henry Houlden, London, United Kingdom

We thank Drs. Tsuji and Mitsui for the comment about COQ2 variants and risk for multiple system atrophy (MSA). While our study of European ancestry patients and controls found no evidence for association of COQ2 variants, [1] we agree that this does not exclude the possibility of variants in this gene underlying MSA in Asian populations. Nevertheless, even within Asia, there are conflicting data on the role of COQ2 in the pathogenesis of MSA. [2-8] We eagerly anticipate additional replication studies involving pathologic-confirmed cases and well-matched controls that explore the role of COQ2 in the etiology of this fatal neurodegenerative illness.

1. Sailer A, Scholz SW, Nalls MA, et al. A genome-wide association study in multiple system atrophy. Neurology 2016;87:1591-1598.

2. Jeon BS, Farrer MJ, Bortnick SF; Korean Canadian Alliance on Parkinson's Disease and Related Disorders. Mutant COQ2 in multiple-system atrophy. N Engl J Med 2014;371:80.

3. Multiple-System Atrophy Research Collaboration. Mutations in COQ2 in familial and sporadic multiple-system atrophy. N Engl J Med 2013;369:233-244.

4. Chen YP, Zhao B, Cao B, et al. Mutation scanning of the COQ2 gene in ethnic Chinese patients with multiple-system atrophy. Neurobiol Aging 2015;36:1222.e7-e11.

5. Sun Z, Ohta Y, Yamashita T, et al. New susceptible variant of COQ2 gene in Japanese patients with sporadic multiple system atrophy. Neurol Genet 2016;2:e54.

6. Wen XD, Li HF, Wang HX, et al. Mutation Analysis of COQ2 in Chinese Patients with Cerebellar Subtype of Multiple System Atrophy. CNS Neurosci Ther 2015;21:626-630.

7. Zhao Q, Yang X, Tian S, An R, Zheng J, Xu Y. Association of the COQ2 V393A variant with risk of multiple system atrophy in East Asians: a case-control study and meta-analysis of the literature. Neurol Sci 2016;37:423-430.

8. Lin CH, Tan EK, Yang CC, Yi Z, Wu RM. COQ2 gene variants associate with cerebellar subtype of multiple system atrophy in Chinese. Mov Disord 2015;30:436-437.

For disclosures, please contact the editorial office at [email protected].

19 October 2016
Association of COQ2 variant with increased risk of MSA in East Asian populations
Shoji Tsuji, Professor
Jun Mitsui, Tokyo, Japan

Sailer et al. conducted a genome-wide association study (GWAS) of 918 patients with multiple system atrophy (MSA) and 3,864 controls and identified several loci potentially associated with MSA. [1] This was the first GWAS ever conducted using such a large sample size, emphasizing the future direction of identifying MSA susceptibility genes using further larger sample sizes. Contrary to a previous study, [2] Sailer et al. found no association of COQ2 with MSA. [1]

Although the authors described that the association of coding variants in COQ2 with MSA did not replicate outside of Japanese MSA samples, [1] there have been reports indicating the association of the COQ2 V393A variant with MSA not only in Japan, [2] but also in other East Asian populations including those in mainland China and Taiwan. [3,4] V393A is a polymorphism commonly present in East Asian populations with carrier frequencies of 1.0-5.2%. [2-7] Although some case-control studies of East Asian populations failed to replicate the association of this variant, [5,6] a recent meta-analysis clearly demonstrated that the pooled odds ratio was 2.05 (95% confidence interval=1.29-3.25, p=0.002). [3] Therefore, the COQ2 V393A variant increases the risk of MSA in East Asian populations.

1. Sailer A, Scholz SW, Nalls MA, et al. A genome-wide association study in multiple system atrophy. Neurology Epub 2016 Sep 14.

2. The Multiple-System Atrophy Research Collaboration. Mutations in COQ2 in familial and sporadic multiple-system atrophy. N Engl J Med 2013;369:233-244.

3. Zhao Q, Yang X, Tian S, et al. Association of the COQ2 V393A variant with risk of multiple system atrophy in East Asians: a case-control study and meta-analysis of the literature. Neurol Sci 2016;37:423-430.

4. Lin CH, Tan EK, Yang CC, Yi Z, Wu RM. COQ2 gene variants associate with cerebellar subtype of multiple system atrophy in Chinese. Mov Disord 2015;30:436-437.

5. Chen YP, Zhao B, Cao B, et al. Mutation scanning of the COQ2 gene in ethnic Chinese patients with multiple-system atrophy. Neurobiol Aging 2015;36:1222.e7-1222.e11.

6. Jeon BS, Farrer MJ, Bortnick SF; Korean Canadian Alliance on Parkinson's Disease and Related Disorders. Mutant COQ2 in multiple-system atrophy. N Engl J Med 2014;371:80.

7. Wen XD, Li HF, Wang HX, et al. Mutation Analysis of COQ2 in Chinese Patients with Cerebellar Subtype of Multiple System Atrophy. CNS Neurosci Ther 2015;21:626-630.

For disclosures, please contact the editorial office at [email protected].

Information & Authors

Information

Published In

Neurology®
Volume 87Number 15October 11, 2016
Pages: 1591-1598
PubMed: 27629089

Publication History

Received: January 17, 2016
Accepted: June 15, 2016
Published online: September 14, 2016
Published in print: October 11, 2016

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Disclosure

A. Sailer was supported in part by the Intramural Research Program of the National Institutes of Health (National Institute of Neurological Disorders and Stroke, National Institute on Aging; project number: Z01 AG000949). She also received funding support from the Multiple System Atrophy Trust, the Medical Research Council UK, and Wellcome Trust. S. Scholz was supported in part by the Intramural Research Program of the National Institutes of Health (National Institute of Neurological Disorders and Stroke, National Institute on Aging; project number: Z01 AG000949). She also received a R25 career development grant by the National Institute of Neurological Disorders and Stroke (grant number: R25 NS065729) and a Rapid Response Innovation Award by the Michael J. Fox Foundation. M. Nalls was supported in part by the Intramural Research Program of the National Institutes of Health (National Institute on Aging; project number: Z01 AG000949). C. Schulte reports no disclosures relevant to the manuscript. M. Federoff was supported in part by the Intramural Research Program of the National Institutes of Health (National Institute on Aging; project number: Z01 AG000949). T. Price was supported in part by the Intramural Research Program of the National Institutes of Health (National Institute of Neurological Disorders and Stroke, National Institute on Aging; project number: Z01 AG000949). A. Lees received funding support from the Multiple System Atrophy Trust, the Medical Research Council UK, Wellcome Trust, and the Reta Lila Weston Institute for Neurological Studies. O. Ross, D. Dickson, K. Mok, N. Mencacci, L. Schottlaender, and V. Chelban report no disclosures relevant to the manuscript. H. Ling receives funding from a CBD Solutions Research Grant and is employed by Reta Lila Weston Institute for Neurological Studies. S. O'Sullivan reports no disclosures relevant to the manuscript. N. Wood received funding support from the Multiple System Atrophy Trust, the Medical Research Council UK, Wellcome Trust, and the Reta Lila Weston Institute for Neurological Studies. B. Traynor was supported in part by the Intramural Research Program of the National Institutes of Health (National Institute on Aging; project number: Z01 AG000949). L. Ferrucci was supported in part by the Intramural Research Program of the National Institutes of Health (National Institute of Neurological Disorders and Stroke, National Institute on Aging; project number: Z01 AG000949). H. Federoff reports no disclosures relevant to the manuscript. T. Mhyre reports no disclosures relevant to the manuscript. H. Morris reports grants from Parkinson's UK and Medical Research Council UK during the conduct of the study and grants from Welsh Assembly Government, personal fees from Teva, personal fees from Abbvie, personal fees from Teva, personal fees from UCB, personal fees from Boehringer-Ingelheim, personal fees from GSK, nonfinancial support from Teva, grants from Ipsen Fund, nonfinancial support from Medtronic, grants from MNDA, grants from PSP Association, grants from CBD Solutions, grants from Drake Foundation, and personal fees from Acorda, outside the submitted work; in addition, Dr. Morris has a patent related to C9ORF72. H. R. M. is a co-applicant on a patent application related to C9ORF72: Method for diagnosing a neurodegenerative disease (PCT/GB2012/052140) pending. G. Deuschl, N. Quinn, H. Widner, A. Albanese, J. Infante, K. Bhatia, and W. Poewe report no disclosures relevant to the manuscript. W. Oertel has served as a consultant for Mundipharma, Novartis, and UCB Pharma; on advisory boards for Boehringer Ingelheim, Merck, Sharp & Dohme, Medtronic, Mundipharma, Neuropore, Novartis, UCB Pharma, and Teva; and received honoraria for presenting lectures from Abbvie, Desitin, Boehringer Ingelheim, Mundipharma, Novartis, Orion Pharma, Schwarz Pharma Neuroscience/UCB, and Teva. He has received scientific grants from the German Ministry of Education and Health, the German Research Foundation, the Charitable Hertie Foundation, the Internaal ParkinsonFonds, the Michael J. Fox Foundation, and Novartis Pharma Germany, and holds shares in Merck, Medigene, and Roche. G. Höglinger has served on the advisory boards for Abbvie, Asceneuron, Bristol-Myers Squibb, Roche, Sellas, and UCB; has received honoraria for scientific presentations from Abbvie, Roche, and UCB; has received research support from CurePSP, the International Parkinson Fonds, the German Academic Exchange Service (DAAD), German Research Foundation (DFG) and the German Ministry of Education and Research (BMBF), and the Sellas Life Sciences Group; and has received institutional support from the German Center for Neurodegenerative Diseases (DZNE). U. Wüllner, S. Goldwurm, M. Pellecchia, J. Ferreira, E. Tolosa, B. Bloem, O. Rascol, and W. Meissner report no disclosures relevant to the manuscript. J. Hardy received funding support from the Multiple System Atrophy Trust, the Medical Research Council UK, and Wellcome Trust. T. Revesz received funding support from the Multiple System Atrophy Trust, the Medical Research Council UK, Wellcome Trust, and the Reta Lila Weston Institute for Neurological Studies. J. Holton received funding support from the Multiple System Atrophy Trust, the Medical Research Council UK, Wellcome Trust, and the Reta Lila Weston Institute for Neurological Studies. T. Gasser and G. Wenning report no disclosures relevant to the manuscript. A. Singleton was supported in part by the Intramural Research Program of the National Institutes of Health (National Institute on Aging; project number: Z01 AG000949). H. Houlden received funding support from the Multiple System Atrophy Trust, the Medical Research Council UK, the Michael J. Fox Foundation, Wellcome Trust, and the Reta Lila Weston Institute for Neurological Studies. Go to Neurology.org for full disclosures.

Study Funding

No targeted funding reported.

Authors

Affiliations & Disclosures

Anna Sailer, MD, PhD
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T. Ryan Price, MS
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2006 Archivas de Nevropsiquiatria (Brazil) 1995-03 Co-Editor in Chief, Movement Disorders Journal and Historical Section Editor 1994-98 Founder Editor, Behavioural Neurology 1994- Neurologia Espana 1994-00 Revista Neurologica, Argentina 1994-95 European Journal of Neurology 1993- Revue Neurologique 1993-03 Brain 1991-95 Journal Neurology, Neurosurgery & Psychiatry 1989-95 Journal of Neurology 1988-95 Journal of Neural Transmission
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1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Helen Ling, MD, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Reta Lila Weston Institute of Neurological Studies
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
CBD Solution Research Grant
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Sean S. O'Sullivan, MD, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
Advisory board for AbbVie pharmaceuticals, Clonmel pharmaceuticals
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Honoraria from UCB Pharmaceuticals, Eisai Pharma, AbbVie, Teva Pharmaceuticals to travel to the Movement Disorders Society annual meetings and other meetings
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Health Service Executive, Ireland. Consultant Neurologist
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
AbbVie pharmaceuticals supporting movement disorders research study in Cork
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Nicholas W. Wood, MD, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Ed board member Neurogenetics 2005-2014 Journal of PD associate ed 2010- Journal of neurodegenerative disease 2010- Progress in Neurology and Psychiatry 2002-2015
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
MRC- UK
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Wellcome trust Parkinson's UK
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Bryan J. Traynor, MD, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) The Italian Football Federation (FIGC), travel expenses; (2) American Academy of Neurology, travel expenses; (3) Cold Spring Harbor Laboratories, travel expenses; (4) The Italian ALS Association (ARISLA), travel expenses; (5) Movement Disorders Society, travel expenses; (6) Wellcome Trust, travel expenses; (7) The Finnish Neurological Society, travel expenses; (8) The NorthEast ALS Consortium (NEALS), travel expenses; (9) UC Irivine, travel expenses; (10) The ALS Hope Foundation, travel expenses; (11) The ALS Association, travel expenses; (12) The American Academy of Neurology, travel expenses; (13) The Motor Neuron Association (UK), travel expenses; (14) Microsoft Research, travel expenses; (15) The Italian Neurological Society, travel expenses; (16) The University of Toronto, travel expenses; (17) The International Congress of Human Genetics, travel expenses; (18) Society for Neuroscience, travel expenses.
Editorial Boards:
1.
Neurology, editorial board, 2011-2011 Journal of Neurology, Neurosurgery, and Psychiatry, editorial board, 2013 - ongoing - Neurobiology of Aging, editorial board, 2015 -
Patents:
1.
I have a patent pending on the clinical testing and therapeutic intervention for the hexanucleotide repeat expansion of the C9ORF72 gene.
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
National Institutes of Health
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) Merck Inc;
Research Support, Government Entities:
1.
(1) Intramural Research Program of the NIH (where I work).
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) The Myasthenia Gravis Foundation; (2) the ALS Association; (3) The Packard Center for ALS Research; (4) FIGC (The Italian Football Federation); (5) the Center for Disease Control and Prevention; (6) Microsoft Research; (7) The Italian ALS Association (ARISLA); (8) The Muscular Dystrophy Association; (9)
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Luigi Ferrucci, MD, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Editorial Board of Pan American Journal of Aging Research, Associate Editor of the Journal of the American Geriatrics Society, Associate Editor of the Journal of Cachexia, Sarcopenia and Muscle, Editorial Board of Geriatr?a y Gerontolog?a (Barcelona, Spain)
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Howard J. Federoff, MD, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
SAB: MedGenesis, LTD; Ovid: SAB; AAHC: Board; CIRM: Board; NAI: Board
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
(1) Experimental Neurology (1999 - Present); (2) Gene Therapy Reviews (2000 - Present); (3) Gene Therapy (2000 - Present); (4) NeuroRx (2002 - Present); (5) The Open Genomics Journal (2007 - Present); (6) Libertas Academica (2008 - Present); (7) Associate Editor, Journal of Parkinson?s Disease (2010 - Present)
Patents:
1.
Utility Patent: US 6,051,428 Issued: April 18, 2000 Title: Rapid production of autologous tumor vaccines Inventors: Y. Fong, H. J. Federoff, and J. D. Rosenblatt Utility Patent: US 6,156,306 Issued: December 5, 2000 Title: Pancreatic beta-cells for allogeneic transplantation without immunosuppression Inventors: M. Brownlee, M. Horowitz, H.J. Federoff and S. Efrat Utility Patent: US 6,252,130 Issued: June 26, 2001 Title: Production of Somatic Mosaicism in Mammals Using a Recombinatorial Substrate Inventor: H.J. Federoff Utility Patent: US 6,491,909 Issued: December 10, 2002 Title: Attenuation of rejected cells transformed with adenovirus E3 Inventors: M. Brownlee, M. Horowitz, H.J. Federoff and S. Efrat Utility Patent: 8,092,791 (WO2001089304A1) Issued: January 10, 2012 Title: Method for Producing HSV Amplicons and Uses Thereof Inventors: H.J. Federoff and W.J. Bowers Utility Patent: 8,119,118 (WO2002056828A3) Issued: February 21, 2012 Title: Helper Virus-Free Herpes Virus Amplicon Particles and Uses Thereof Inventors: HJ Federoff, WJ Bowers, J Frelinger, R Willis, T Evans, S Dewhurst, KA Tolba, JD Rosenblatt Utility Patent: 20040115671 (WO2002057496A9) Issued: 6/17/04 Title: Gene Expression Profiling of Endothelium in Alzheimer?s Disease Inventors: B. Zlokovic, H. J. Federoff Provisional Patent: Converted 60/250,079 Filing Date: 11/30/00 Title: Development of Helper virus free HSV Amplicon vectors for Gene Therapy of Hematologic Malignancies Inventors: K. Tolba, H.J. Federoff, W.J. Bowers, and J. Rosenblatt Provisional Patent: Converted US 60/385,230 Filing Date: 5/31/2002 Title: Integrated HSV Amplicon Vector Inventors: H. J. Federoff and W. J. Bowers Provisional Patent: Pending US 60/356,964 Filing Date: 2/13/2002 Title: Compositions and Methods for the Treatment of Parkinson?s Disease Inventors: Howard J. Federoff and Renee M. Miller Provisional Patent: Converted US 60/359,613 Filing Date: 2/25/2002 Title: Glucocorticoid-Regulated VEGF Expression via Plasmid-based Delivery Inventors: H.J. Federoff and W. J. Bowers Provisional Patent: Pending US 60/480,112 Filing Date: 6/20/03 Title: Prevention of Treatment of Deficits that Arise in Connection of or Injuries to the Nervous System Inventors: H.J. Federoff, W.J. Bowers, V. Arvanian, and L. Mendell Provisional Patent: Pending US 60/518,474 Filing Date: 11/07/03 Title: Compositions and Methods of Treating Neurological Disorders Inventors: H. J. Federoff and W. J. Bowers Provisional Patent: Pending US 60/700,758 Filling Date: 07/22/2005 Title: Biomarkers of Neurodegenerative Disease Inventors: Paul D. Coleman, Howard J. Federoff, Kathleen Maguire-Zeiss, Timothy R. Mhyre, Roger M. Kurlan, Christopher Cox, Frederick Marshall Provisional Patent: Pending US 60/700,565 Filing Date: 7/19/2006 Title: Alpha-synuclein antibodies and methods related thereto Inventors: H.J. Federoff, K. Maguire-Zeiss, and M. Sullivan Provisional Patent: Pending US 60/941,849 Filing Date: 06/04/2007 Title: Herpes Simplex Virus Amplicon Vectors Derived From Primary Isolates Inventors: S. Dewhurst, W.J. Bowers, H.J. Federoff, J.G. Frelinger, M.C. Keefer Application No.: PCT/US2006/021806 European Provisional Patent: 06784589.1 Filing Date: 06/05/2006 Title: Herpes Virus-Based Compositions And Methods Of Use In The Prenatal And Perinatal Periods Inventors: HJ Federoff and W.J. Bowers Applicant: University of Rochester US Provisional Patent Application PCT/US12/045727; 13/543,044 Filing Date: 07/06/2012 Title: System and Method for Performing Pharmacovigilance Inventors: HJ Federoff and O Frieder Applicant: Georgetown University Utility Patent Patent 9,305,140 Filing Date: 7/16/12 Title: System and Method of Applying State of Being to Health Care Delivery Inventors: HJ Federoff, E Burger, O Frieder Applicant: Georgetown University US Provisional Patent Application PCT/US14/026583 Filing Date: 3/13/14 Title: Small Molecule LRRK2 and ERK5 inhibitors Inventors: HJ Federoff, S Shah Applicant: Georgetown University US Provisional Patent Application 61/879,553 Filing Date: 9/18/13 Title: Treating Neurodegenerative Disease with Fenofibrate and Analogs Thereof Inventors: HJ Federoff, X Su, M Polymeropoulos Applicant: Georgetown University US Provisional Patent Application 61/893,762 Filing Date: 10/21/13 Title: Biomarkers for Memory Loss PCT application No. PCT/US14/061578 entitled, ?BioMarkers for Memory Loss? filed on October 21, 2014 Inventors: HJ Federoff, ME Mapstone, MS Fiandaca, AK Cheema Applicant: Georgetown University US Provisional Patent Application 61/986,555 Filing Date: 4/30/14 Title: Metabolic and Genetic Biomarkers for Memory Loss Inventors: HJ Federoff, ME Mapstone, MS Fiandaca, AK Cheema Applicant: Georgetown University U.S. Provisional Patent application 62/002,453 Filing Date: May 23, 2014 Title: Exosomal Biomarkers for Memory Loss Inventors: HJ Federoff, ME Mapstone, MS Fiandaca U.S. Provisional Patent application 62/003,666 and 62/003,357 Filing Date: May 29, 2014 Title: Genetic Biomarkers for Memory Loss Inventors: HJ Federoff, ME Mapstone, MS Fiandaca, Y Gusev U.S. Provisional Patent application Filing Date: May 27, 2014 Title: Metabolic Biomarkers for Memory Loss Inventors: HJ Federoff, ME Mapstone, MS Fiandaca, AK Cheema U.S. Provisional Patent application Filing Date: October 16, 2014 Title: Protein Biomarkers for Memory Loss Inventors: HJ Federoff, ME Mapstone, MS Fiandaca, AK Cheema
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
(1) MedGenesis, scientific advisor; (2) Ovid, SAB member (3) AAHC, Board member (4) ASENT, Immediate past president (5) NAI, Board member
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
W81XWH-09-1-0107 (Federoff, Howard J.) 01/19/09-08/31/16 Department of Defense Validation of Peripheral Biomarkers of Traumatic Brain Injury? W81XWH-09-1-0103 (Federoff, Howard J.) 01/05/09-01/04/17 Department of Defense ?Recruitment and Sample Collection for Antecedent Biomarker Discovery in Parkinson?s Disease? NINDS intramural sponsored clinical trial ?A Phase 1 Open-Label Dose Escalation Safety Study of Convection-enhanced Delivery (CED) of Adeno-Associated Virus Encoding Glial Cell Line-Derived Neurotrophic Factor (AAV2-GDNF) in Subjects with Advanced Parkinson?s Disease.? Protocol Number: 12-N-0137 Role: Co-Investigator WX81XWH-11-49-0126 (Federoff, Howard J) 05/30/14- 04/30/17 Department of Defense ?PGC-1α Therapy for Parkinsonian Neurodegeneration? Atlantic Neurosciences Institute (Federoff, Howard J) 02/07/14-12/31/16 ?Exploratory Gene Expression Analysis of Childhood Autism? W81XWH-16-1-0148 (Federoff, Howard J) 05/02/16-05/01/18 Department of Defense ?Discovery and Validation of Peripheral Biomarkers of Traumatic Brain Injury: A Risk Factor for Parkinson?s Disease?
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
Ovid, $65,000. 125,000 options MedGenesis, 450,000 shares
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Timothy R. Mhyre, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Huw R. Morris, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
1) Solvay Panel Member 2) Boerhinger-Ingelheim 3) Solvay 4) Accorda 5) Exenatide
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
1) Travel and honoraria - Lecture - Wellcome Trust, 2012 2) Teva Movement Disorders Society 2012 3) Teva Lecture 2012 4) UCB Lecturer 2012
Editorial Boards:
1.
1) Editorial Board Parkinson's disease 2009-2015 2) Editorial Board Journal of Neurology
Patents:
1.
H. R. M is a co-applicant on a patent application related to C9ORF72 - Method for diagnosing a neurodegenerative disease (PCT/GB2012/052140) pending.
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Ipsen Fund Research Fellowship 2009-2010
Research Support, Government Entities:
1.
Welsh Assembly Government - Research Fellowship 2009-2012 Medical Research Council (UK) 2008-2010 G0700943 Medical Research Council (UK) 2012-2015
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Parkinson's disease society J-0804 2009-2011 Progressive Supranuclear Palsy Association 2007-2009 Motor Neuron Disease Association 2010- Motor Neuron Disease Association 2010-2014
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Günther Deuschl, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
Medtronic, Sapiens, Britannica, Boston Scientific
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Medtronic, Desitin, UCB
Editorial Boards:
1.
Movement Disorders, editor 2004-2010 Aktuelle Neurologie, co-editor 1994-now Several journals, editorial board member
Patents:
1.
NONE
Publishing Royalties:
1.
Thieme publishers: Referenzreihe Neurologie
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Niall Quinn, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1)Commercial entity, type of payment. Lecture Honorarium Teva/Lundbeck March 2015 (2)Non-profit entity, type of payment. Webinar honorarium Klinik f?r Neurologie KantonsspitalCH-9007 St.Gallen Switzerland November 2015
Editorial Boards:
1.
(1)Journal of Parkinson's Dsease Editorial Board (2010-) (2)Journal of Movement Disorders (S.Korea)International Editorial Board(2008-) (3)Movement Disorders Clinical Practice Editorial Board,(2014-15) (4)Parkinsonism and Related Disorders Editorial Board,(2015-)
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Hakan Widner, MD, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Alberto Albanese, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Speaker?s honoraria from Allergan, Merz, Ipsen and Medtronic
Editorial Boards:
1.
(1) European Journal of Neurology, Associate Editor, current; (2) Frontiers in Movement Disorders, Editor, current
Patents:
1.
NONE
Publishing Royalties:
1.
(1) Botulinum Toxin: Clinical Practice and Science, Saunders Elsevier, 2009
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Jon Infante, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Kailash P. Bhatia, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Funding for travel: (1) GlaxoSmithKline, (2) Orion Corporation, (3) Ipsen, (4) Merz Pharmaceuticals, LLC 5) Sun Pharmaceuticals Ltd Speaker honoraria: (1) GlaxoSmithKline, (2) Ipsen, (3) Merz Pharmaceuticals, LLC, (4) Sun Pharmaceutical Industries Ltd.
Editorial Boards:
1.
(1) Movement Disorders, Associate Editor (2) Therapeutic Advances in Neurological Disorders, Editorial Board 3) Co- Editor in Chief - Movement disorders Clinical Practise
Patents:
1.
NONE
Publishing Royalties:
1.
(1) Oxford Specialist Handbook of Parkinson?s Disease and Other Movement Disorders, Oxford University Press, 2008 2) Marsdens book of Movement disorder, Oxford Universty Press 2012 3) Lancet Neurology review article- 2012
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Consultancy work for Allergan, Ipsen, Merz
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
1) Wellcome Trust MRC strategic neurodegenerative disease initiative award (WT089698), (2) Parkinson's UK 3) Dystonia Coalition 4) The Bachmann-Strauss Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Werner Poewe, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
Werner Poewe has received consultancy and lecture fees from Abbott, Astra Zeneca, Teva, Novartis, GSK, Boehringer-Ingelheim, UCB, Orion Pharma, Abbott and Merck Serono in relation to clinical drug development programmes for PD.
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Werner Poewe has received consultancy and lecture fees from Abbott, Astra Zeneca, Teva, Novartis, GSK, Boehringer-Ingelheim, UCB, Orion Pharma, Abbott and Merck Serono in relation to clinical drug development programmes for PD.
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
1. Therapeutics of Parkinson's Disease and Other Movement Disorders, Hallett M, Poewe W, Wiley, 2008 2. Non-motor symptoms of Parkinson's Disease, Chaudhuri R, Poewe W, Oxford University Press, 2009 3. Parkinson-Syndrome und andere Bewegungsst?rungen Hrsg. Oertel W, Deuschl G, Poewe W, Thieme 2011
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Werner Poewe has received consultancy and lecture fees from Abbott, Astra Zeneca, Teva, Novartis, GSK, Boehringer-Ingelheim, UCB, Orion Pharma, Abbott and Merck Serono in relation to clinical drug development programmes for PD.
Speakers' Bureaus:
1.
Werner Poewe has received consultancy and lecture fees from Abbott, Astra Zeneca, Teva, Novartis, GSK, Boehringer-Ingelheim, UCB, Orion Pharma, Abbott and Merck Serono in relation to clinical drug development programmes for PD.
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Michael J. Fox Foundation 1. ?Validation of Dyskinesia Rating Scales?, Goetz C, 2009 2.
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Wolfgang Oertel, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
(1) Boehringer Ingelheim, (2) Medtronic, (3) Merck-Sharp and Dohme, (4) Novartis, (5) UCB (6) Mundipharma (7) Teva (8) Adamas
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) Boehringer Ingelheim, (2) Novartis (3) Orion-Pharma, (4) UCB (6) Teva (7) Desitin (8) Mundipharma (9) Glaxo Smith Kline (10)Abbvie
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
see point 1 and point 3
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) Novartis
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) Michael J Fox Foundation, (2) International Parkinson Foundation, (3) German Research Foundation (4) WH Oertel is Hertie Senior Research Professor supported by the Charitable Hertie Foundation, Frankfurt, Germany
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
(1) Roche 250 (3) Merck Darmstadt 300
Legal Proceedings:
1.
NONE
Günter U. Höglinger, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
(1) Asceneuron, (2) Abbvie, (3) Bristol-Myers Squibb, (4) Roche, (5) UCB
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) Abbvie, (2) Roche, (3) UCB, (4) Movement Disorders Society
Editorial Boards:
1.
NONE
Patents:
1.
(1) Method for the treatment of neurodegenerative diseases. PCT/EP2015/068734.
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) Sellas Life Sciences Group
Research Support, Government Entities:
1.
(1) Bayerische Forschunsallianz, (2) German Ministry of Education and Research (BMBF), (3) German Academic Exchange Service (DAAD), (4) German Research Foundation (DFG), (5) German Center for Neurodegenerative Diseases (DZNE)
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) CurePSP, (2) International Parkinson Foundation, (3) NOMIS Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Ullrich Wüllner, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
(1) Advisory board UCB Pharma
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Bayer AG,travel and speaker honoraria Bristol-Myers-Squibb,travel and speaker honoraria Daiichi Sankyo Deutschland GmbH,travel and speaker honoraria UCB Pharma,travel and speaker honoraria Sanofi-Aventis Deutschland GmbH,travel and speaker honoraria Zambon GmbH, travel and speaker honoraria
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
1)German Federal Ministry of Education and Research (BMBF) through the EpiPD (Epigenomics of Parkinson?s disease) project, under the auspices of the bilateral Epigenomics of Common and Age-related Diseases Programme (grant # 01KU1403B). 2)EU/EFPIA Innovative Medicines Initiative Joint Undertaking [Aetionomy [grant number 115568]).
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
1) Deutsche Parkinson Vereinigung (dPV); Hans Tauber Stiftung 2) The Internationale Parkinson Fonds gGMBH
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Stefano Goldwurm, MD, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
S. Goldwurm received grants from Italian Telethon Foundation: grant n.GTB12001B ?Parkinson Institute Biobank? (2012-17). S. Goldwurm is coordinator of the Italian consortium of the COURAGE-PD (COmprehensive Unbiased Risk factor Assessement for Genetics and Environment in PD) funded by JPND (The EU Joint Programme ? Neurodegenerative Disease Research), 2014- 17.
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Maria Teresa Pellecchia, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Joaquim Ferreira, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Eduardo Tolosa, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
honoraria as a speaker for UCB, Boeringer Ingelheim, Novartis, Abbot, Medtronic, Solvay, GSK
Editorial Boards:
1.
Editorial advisory board member for Journal Neurological Sciencies
Patents:
1.
Date of filing: 17.12.2015 Title: method for the sub-classification of patients suffering from parkinson disease
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
The Michael J Fox foundation for Parkinson's Disease Novartis UCB Abbot Teva
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
-Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS)Principal Investigator From 2008 to 2013 - European Project for Mendelian Forms of Parkinson's Disease ( MEFOPA) PI040438 Principal Investigator from 2010 to 2012
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Bastiaan R. Bloem, MD, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Abbvie (speaker's fee) Zambon (speaker's fee)
Editorial Boards:
1.
Member editorial board, Movement Disorders (until 2010) Member editorial board, Physiotherapy Canada Editor-in-chief, Tijdschrift voor Neurologie & Neurochirurgie (until 2013) Associate editor, Journal of Parkinson's Disease (since 2013)
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Radboud University Nijmegen Medical Center
Consultancies:
1.
? Danone (commercial entity) Glaxo-Smith-Kline (commercial entity) UCB (commercial entity) Adamas (commercial entity) Teva (commercial entity) Zambon (commercial entity)
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
? MyCognition
Research Support, Government Entities:
1.
? Grant of the Parkinson Society Canada?s National Research Program (funding for full PhF program for Eveline Pasman). Role: co-investigator (project leader: Dr. Mark Carpenter), 2014 ? Grant of Euregio (European Fund Regional Development), with co-funding by the German Parkinson Patient Foundation and the Dutch province of Gelderland Role: project leader (together with Marten Munneke), 2014
Research Support, Academic Entities:
1.
? Joint Programme - Neurodegenerative Disease Research (JPND) ? Radboud University Medical Centre ? Schr?dinger Stipendium
Research Support, Foundations and Societies:
1.
(1)National Parkinson Foundation, (2)SBOH, (3)Stichting Parkinson Fonds, (4)Stichting Parkinson Nederland, (5)Fred Foundation, (6) Hersenstichting, (7) The Cure Parkinson's trust
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Olivier Rascol, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
AbbVie Britannia Lundbeck Merck MundiPharma Sanofi Servier Teva UCB XenoPort Zambon
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Boehringer Ingelheim MundiPharma
Editorial Boards:
1.
Movement Disorders
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
AbbVie Britannia Lundbeck Merck MundiPharma Sanofi Servier Teva UCB XenoPort Zambon
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Boehringer Ingelheim Lundbeck Teva UCB
Research Support, Government Entities:
1.
Agence Nationale de la Recherche CHU de Toulouse France-Parkinson INSERM-DHOS Recherche Clinique Translationnelle MJFox Foundation
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
France Parkinson (CoPark), MJ Fox Foundation (Simvastatine)
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Wassilios G. Meissner, MD, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
Jambon France
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Speaking fees from TEVA/Lundbeck, ORKYN; travel grants from Abbie.
Editorial Boards:
1.
Journal of Neural Transmission, field editor neurology and translational studies
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
Speaking fees from TEVA/Lundbeck, ORKYN; travel grants from Abbie.
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
French Health Ministry, the European Community, ANR, LABEX Excellence Initiative.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Michael J Fox Foundation, France Parkinson, PSP-France and MSA Coalition.
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
John A. Hardy, PhD, MD(Hon)
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
Consulting for Eisai and Lilly on Alzheimer's and Parkinson's diseases
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Eisai
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Tamas Revesz, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
IV International Symposium on Parkinson?s disease and movement disorders - sponsered by Boehringer-Ingelheim - honorarium Teaching visiting Turkish Neurologists Teaching visiting Swedish Neurologists ADPD Meeting 2013 - Florence
Editorial Boards:
1.
Associate Editor: Journal of Parkinson's disease Member of Editorial Advisory Board: Neuropathology and Applied Neurobiology Associate Editor Journal of Parkinson's Disease
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Merck Serono - Consultancy
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Orion Pharma: Research Grant (Does Levodopa have toxic effects in Parkinson?s disease brain?) CBD Solutions: Disease progression in corticobasal degeneration
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
1.) Alzheimer?s Research Trust (PI: T Revesz, J Holton; M Rossor; A. Lees), (ART/PG2007/2), (ART/PG2007/2); Title: Clinicopathol. correlation in frontotemporal lobar degeneration, 1/1/2008-31/12, 2011 2.) Alzheimer?s Research Trust Research Fellowship; (F Plattner ? fellow;T Revesz ? sponsor), (ART/RD2005/1), Title: Analysis of molec. mechanisms in tau hyperphosphorylation, 1/3/2006?31/8/2009 3.) European Commission, Programme Grant (LSHM-CT-2004-503039), BrainNet Europe II. Network of Excellence, one of UK Components (PI T Revesz, AJ Lees, JL Holton); 01/07/2007-30/06/2009 4.) Sarah Matheson Trust (PI: T Revesz; J Holton), (Margaret Watson Memorial Grant) Title: The role of p25 in GCI formation in multiple system atrophy; 1/1/2008?31/12/2008 5.) Sarah Matheson Trust, (J. Holton, T Revesz, H. Houlden, J. Hardy, AJ Lees), Title: The central role of oligodendroglia in the pathogenesis of multiple system atrophy, 01/03/2008 - 28/02/2011 6.) Parkinson?s Disease Society, UK (PI: T Revesz; J Holton) (PDS/4062), Titlle: Support for Parkinson?s Disease brain banking, 15/9/2004 ? 31/12/2007 7.) Parkinson's UK (Parkinson's Disease Society): Understanding pathological spread in Parkinson's disease. 2010-2013. PI: Tamas Revesz 8.) MRC/Wellcome Trust: Understanding Parkinson's disease: lessons from biology. 2010-2015. Co-applicant.
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Janice L. Holton, MD, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
1. Merck-Serono. Agreement to cover travel expenses to give a seminar in Geneva 8.4.2011.
Editorial Boards:
1.
Member of the editorial board Neuropathology Applied Neurobiology 2007- present Executive Editor Neuropathology Applied Neurobiology 2012- 2014 Editor-in-Chief Neuropathology Applied Neurobiology 2014
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
University College London, full time employment.
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
1.Alzheimer?s Research Trust. January 2008 ? December 2010 2.The Margaret Watson Memorial Trust Grant from The Sarah Matheson Trust. January 2008 ? December 2008 3. Action Medical Research November 2007 ? October 2009 4. Brain Net Europe: Support for the Queen Square Brain Bank for Neurological Disorders July 2007 ? June 2009 5.The Sarah Matheson Trust. January 2009 ? December 2011 6. Myositis Support Group June 2009 ? May 2010 and July 2015 - June 2016 7. The Multiple System Atrophy Trust. August 2012 ? July 2014 and June 2015 - January 2017 8. Michael J Fox Foundation for Parkinson?s Research December 2010 ? November 2011 July 2014-2015 9. Alzheimer?s Research UK March 2012 - February 2013 10. MSA Coalition July 2015 - June 2016 11. King Baudouin Foundation Sophia Fund May 2016-April 2018
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Thomas Gasser, MD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
(1) Joint programming in neurodegenerative diseases
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) MedUpdate: speakers honoraria and funding for travel (2) Movement Disorders Society: funding for travel (3) Michael J Fox Foundation: funding for travel (4) UCB Pharma
Editorial Boards:
1.
(1) Parkinsonism and Related Disorders, editorial board member, since 2007; (2) Movement Disorders, editorial board member; (3) Journal of Neurology, editorial board member
Patents:
1.
(1) KASPP (LRRK2) Gene, its Production and Use for the Detection and Treatment of Neurodegenerative Diseases
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
(1) Novartis; (2) Merck-Serono; (3) Schwarz Pharma; (4) Boehringer Ingelheim; (5) Valeant Pharma
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) Novartis Pharma AG
Research Support, Government Entities:
1.
(1) ERA-Net Neuron, BMBF, 01EW0908, PI, 2009-2012; (2) MultiSyn, EU, PI 2014 - 2018 (3) Courage-PD, BMBF Joint programming, 2013 - 2017 (4) European Comission
Research Support, Academic Entities:
1.
(1) DZNE, Helmholtz Association, PI, 2009 ff
Research Support, Foundations and Societies:
1.
(1) Michael J Fox Foundation (2) The German Research Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Gregor K. Wenning, MD, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) Astra-Zeneca Speaker Honoraria (2) Lundbeck Speaker Honoraria
Editorial Boards:
1.
Clinical Autonomic Research
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
(1) Astra Zeneca
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) Austrian Science Foundation, FWF SFB F4414, 2015-2019
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Andrew B. Singleton, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) 23andMe, travel payment
Editorial Boards:
1.
No financial compensation, but serve on: Annals of Neurology Lancet Neurology Neurogenetics Neurodegenerative Diseases Brain Journal of Parkinson's Disease
Patents:
1.
Patent pending for panel of markers to diagnose stroke
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH Intramural funding Department of Defense, W81XWH-09-2-0128, PI, 2009-2011
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Henry Houlden, MD, PhD
Authors' affiliations are listed at the end of the article.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
My laboratory is funded by: The Medical Research Council (MRC) UK, The BRT, The MDA USA, Muscular Dystrophy UK, Rosetrees Trust, The Wellcome Trust and the National Institute for Health Research (NIHR) UCLH/UCL Biomedical Research Centre.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
My laboratory is funded by: The Dystonia Medical Research Foundation (DMRF), The Parkinson's Disease Foundation (PDF), National Organisation for Rare Disorders (NORD) and The Brain Research Trust (BRT). The National Institute for Health Research (NIHR) UCLH/UCL Biomedical Research Centre.
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
On behalf of the European Multiple System Atrophy Study Group and the UK Multiple System Atrophy Study Group

Notes

Correspondence to Dr. Houlden: [email protected] or Dr. Scholz: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by Wellcome Trust.
Coinvestigators are listed at Neurology.org.

Author Contributions

Patient recruitment: H.H., A.S., N.W., G.K.W., A.L., W.P., W.O., U.W., S.G., M.T.P., T.G., C.S., O.R., D.D., H.L., S.O., A.L., L.F., H.M., G.D., N.Q., H.W., A.A., J.I., K.B., W.P., W.O., G.U.H., U.W., S.G., M.T.P., J.F., E.T., B.B., J.A.H., T.R., J.H., D.B., V.K., P.C., H.R., J.S., A.S., E.R., G.M., C.C., P.B., L.D.T., O.R., R.D., T.G., A.A., W.M., K.O., E.D., N.P., M.J.L., I.S., G.C.-B., S.C., L.S., T.K., F.T., A.F., S.A.S., A.L. R.P., C.N., O.H., V.R., F.D., H.B., J.K., A.R., C.P., G.F., F.D., M.S., M.I.P., A.P., M.S., D.B., O.R., N.R., N.G., Y.B., H.S., Y.M., M.P., and R.B. Sample preparations: A.S., J.L.H., T.R., S.W.S., C.S., H.H., and O.R. Genotyping: A.S., S.W.S, H.H., A.B.S., and N.E.M. Writing: A.S., S.W.S, M.A.N., H.H., A.B.S, M.F., R.P., and L.V.S. Conceptualization and design: H.H., A.B.S, J.A.H, A.S., S.W.S, and M.A.N. Critical review of manuscript (all authors); Supervision: H.H., A.B.S., and J.A.H.

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Cited By
  1. Genome sequence analyses identify novel risk loci for multiple system atrophy, Neuron, (2024).https://doi.org/10.1016/j.neuron.2024.04.002
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  3. Multiple system atrophy: an update and emerging directions of biomarkers and clinical trials, Journal of Neurology, 271, 5, (2324-2344), (2024).https://doi.org/10.1007/s00415-024-12269-5
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  4. Genetics of Multiple System Atrophy and Progressive Supranuclear Palsy: A Systemized Review of the Literature, International Journal of Molecular Sciences, 24, 6, (5281), (2023).https://doi.org/10.3390/ijms24065281
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  5. SNCA Gene Methylation in Parkinson’s Disease and Multiple System Atrophy, Epigenomes, 7, 1, (5), (2023).https://doi.org/10.3390/epigenomes7010005
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  6. Diagnosing multiple system atrophy: current clinical guidance and emerging molecular biomarkers, Frontiers in Neurology, 14, (2023).https://doi.org/10.3389/fneur.2023.1210220
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  8. C9orf72 genetic screening in amyotrophic lateral sclerosis patients from Serbia, GenetikaABI Genetika, 55, 1, (1-18), (2023).https://doi.org/10.2298/GENSR2301001M
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  9. Large-scale genome sequencing redefines the genetic footprints of high-altitude adaptation in Tibetans, Genome Biology, 24, 1, (2023).https://doi.org/10.1186/s13059-023-02912-1
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  10. The genetic basis of multiple system atrophy, Journal of Translational Medicine, 21, 1, (2023).https://doi.org/10.1186/s12967-023-03905-1
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