Skip to main content
AAN.com

Abstract

Objectives:

Previous associations between mitochondrial DNA (mtDNA) and idiopathic Parkinson disease (PD) have been inconsistent and contradictory. Our aim was to resolve these inconsistencies and determine whether mtDNA has a significant role in the risk of developing PD.

Methods:

Two-stage genetic association study of 138 common mtDNA variants in 3,074 PD cases and 5,659 ethnically matched controls followed by meta-analysis of 6,140 PD cases and 13,280 controls.

Results:

In the association study, m.2158T>C and m.11251A>G were associated with a reduced risk of PD in both the discovery and replication cohorts. None of the common European mtDNA haplogroups were consistently associated with PD, but pooling of discovery and replication cohorts revealed a protective association with “super-haplogroup” JT. In the meta-analysis, there was a reduced risk of PD with haplogroups J, K, and T and super-haplogroup JT, and an increase in the risk of PD with super-haplogroup H.

Conclusions:

In a 2-stage association study of mtDNA variants and PD, we confirm the reduced risk of PD with super-haplogroup JT and resolve this at the J1b level. Meta-analysis explains the previous inconsistent associations that likely arise through sampling effects. The reduced risk of PD with haplogroups J, K, and T is mirrored by an increased risk of PD in super-haplogroup HV, which increases survival after sepsis. Antagonistic pleiotropy between mtDNA haplogroups may thus be shaping the genetic landscape in humans, leading to an increased risk of PD in later life.

Get full access to this article

View all available purchase options and get full access to this article.

Supplementary Material

File (contributors.docx)
File (figure_e-1.pptx)
File (table_e-1.docx)
File (table_e-2.docx)

REFERENCES

1.
Schapira AH, Cooper JM, Dexter D, et al. Mitochondrial complex I deficiency in Parkinson's disease. Lancet 1989;1:1269.
2.
Langston JW, Forno LS, Tetrud J, et al. Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann Neurol 1999;46:598–605.
3.
Betarbet R, Sherer TB, MacKenzie G, et al. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 2000;3:1301–1306.
4.
Matsumine H, Saito M, Shimoda-Matsubayashi S, et al. Localization of a gene for an autosomal recessive form of juvenile parkinsonism to chromosome 6q25.2-27. Am J Hum Genet 1997;60:588–596.
5.
Valente EM, Abou-Sleiman PM, Caputo V, et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 2004;304:1158–1160.
6.
Torroni A, Huoponen K, Francalacci P, et al. Classification of European mtDNAs from an analysis of three European populations. Genetics 1996;144:1835–1850.
7.
Simon DK, Mayeux R, Marder K, et al. Mitochondrial DNA mutations in complex I and tRNA genes in Parkinson's disease. Neurology 2000;54:703–709.
8.
Mehta P, Mellick GD, Rowe DB, et al. Mitochondrial DNA haplogroups J and K are not protective for Parkinson's disease in the Australian community. Mov Disord 2009;24:290–292.
9.
Latsoudis H, Spanaki C, Chlouverakis G, et al. Mitochondrial DNA polymorphisms and haplogroups in Parkinson's disease and control individuals with a similar genetic background. J Hum Genet 2008;53:349–356.
10.
Gaweda-Walerych K, Maruszak A, Safranow K, et al. Mitochondrial DNA haplogroups and subhaplogroups are associated with Parkinson's disease risk in a Polish PD cohort. J Neural Transm 2008;115:1521–1526.
11.
Ghezzi D, Marelli C, Achilli A, et al. Mitochondrial DNA haplogroup K is associated with a lower risk of Parkinson's disease in Italians. Eur J Hum Genet 2005;13:748–752.
12.
Huerta C, Castro MG, Coto E, et al. Mitochondrial DNA polymorphisms and risk of Parkinson's disease in Spanish population. J Neurol Sci 2005;236:49–54.
13.
Pyle A, Foltynie T, Tiangyou W, et al. Mitochondrial DNA haplogroup cluster UKJT reduces the risk of PD. Ann Neurol 2005;57:564–567.
14.
Ross OA, McCormack R, Maxwell LD, et al. mt4216C variant in linkage with the mtDNA TJ cluster may confer a susceptibility to mitochondrial dysfunction resulting in an increased risk of Parkinson's disease in the Irish. Exp Gerontol 2003;38:397–405.
15.
van der Walt JM, Nicodemus KK, Martin ER, et al. Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease. Am J Hum Genet 2003;72:804–811.
16.
Otaegui D, Paisan C, Saenz A, et al. Mitochondrial polymorphisms in Parkinson's disease. Neurosci Lett 2004;370:171–174.
17.
Simon-Sanchez J, Schulte C, Bras JM, et al. Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat Genet 2009;41:1308–1312.
18.
Fung HC, Scholz S, Matarin M, et al. Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data. Lancet Neurol 2006;5:911–916.
19.
Spencer CC, Plagnol V, Strange A, et al. Dissection of the genetics of Parkinson's disease identifies an additional association 5′ of SNCA and multiple associated haplotypes at 17q21. Hum Mol Genet 2011;20:345–353.
20.
Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007;81:559–575.
21.
Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007;447:661–678.
22.
Borenstein M, Hedges L, Higgins J, Rothstein H. Comprehensive Meta-Analysis Version 2. Englewood, NJ: Biostat; 2005.
23.
van Oven M, Kayser M. Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum Mutat 2009;30:E386–E394.
24.
Maximov V, Martynenko A, Hunsmann G, et al. Mitochondrial 16S rRNA gene encodes a functional peptide, a potential drug for Alzheimer's disease and target for cancer therapy. Med Hypotheses 2002;59:670–673.
25.
Tajima H, Niikura T, Hashimoto Y, et al. Evidence for in vivo production of Humanin peptide, a neuroprotective factor against Alzheimer's disease-related insults. Neurosci Lett 2002;324:227–231.
26.
Gomez-Duran A, Pacheu-Grau D, Lopez-Gallardo E, et al. Unmasking the causes of multifactorial disorders: OXPHOS differences between mitochondrial haplogroups. Hum Mol Genet 2010;19:3343–3353.
27.
Baudouin SV, Saunders D, Tiangyou W, et al. Mitochondrial DNA and survival after sepsis: a prospective study. Lancet 2005;366:2118–2121.
28.
Liu G, Zhang C, Yin J, et al. alpha-Synuclein is differentially expressed in mitochondria from different rat brain regions and dose-dependently down-regulates complex I activity. Neurosci Lett 2009;454:187–192.
29.
Buttner S, Bitto A, Ring J, et al. Functional mitochondria are required for alpha-synuclein toxicity in aging yeast. J Biol Chem 2008;283:7554–7560.
30.
Hsu LJ, Sagara Y, Arroyo A, et al. alpha-Synuclein promotes mitochondrial deficit and oxidative stress. Am J Pathol 2000;157:401–410.

Information & Authors

Information

Published In

Neurology®
Volume 80Number 22May 28, 2013
Pages: 2042-2048
PubMed: 23645593

Publication History

Received: November 20, 2012
Accepted: February 21, 2013
Published online: May 3, 2013
Published in print: May 28, 2013

Permissions

Request permissions for this article.

Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.

Study Funding

G.H. is a Parkinson’s UK Senior Fellow. P.F.C. is a Wellcome Trust Senior Fellow in Clinical Science and an NIHR Senior Investigator who also receives funding from the Wellcome Centre for Mitochondrial Research, the Medical Research Council (UK) Translational Muscle Centre, the UK NIHR Biomedical Research Centre for Ageing and Age-Related Disease, and NIHR Dementia Biomedical Research Unit awards to the Newcastle upon Tyne Foundation Hospitals NHS Trust. M.N. and A.S. are supported in part by the Intramural Research Program of the National Institute on Aging, NIH, Department of Health and Human Services, project number Z01 AG000949-06. D.P.B. is supported by Parkinson's UK and has been the recipient of a Raymond and Beverly Sackler studentship.

Authors

Affiliations & Disclosures

Gavin Hudson, PhD
From the Wellcome Centre for Mitochondrial Research (G.H., P.F.C.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Laboratory of Neurogenetics (M.N., A.B.S.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical Neurosciences (J.R.E., D.P.B., S.W.-R., C.H.W.-G.), University of Cambridge, Cambridge; Division of Neurosciences (K.E.M., R.A.B.), University of Birmingham, Edgbaston, Birmingham; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (H.R.M.), Cardiff University School of Medicine, Cardiff; Department of Molecular Neuroscience (J.H., N.E.W.), Institute of Neurology, University College London, London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.
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
Mike Nalls, PhD
From the Wellcome Centre for Mitochondrial Research (G.H., P.F.C.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Laboratory of Neurogenetics (M.N., A.B.S.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical Neurosciences (J.R.E., D.P.B., S.W.-R., C.H.W.-G.), University of Cambridge, Cambridge; Division of Neurosciences (K.E.M., R.A.B.), University of Birmingham, Edgbaston, Birmingham; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (H.R.M.), Cardiff University School of Medicine, Cardiff; Department of Molecular Neuroscience (J.H., N.E.W.), Institute of Neurology, University College London, London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.
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.
NIH employee (2005-current)
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
Jonathan R. Evans, MRCP, PhD
From the Wellcome Centre for Mitochondrial Research (G.H., P.F.C.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Laboratory of Neurogenetics (M.N., A.B.S.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical Neurosciences (J.R.E., D.P.B., S.W.-R., C.H.W.-G.), University of Cambridge, Cambridge; Division of Neurosciences (K.E.M., R.A.B.), University of Birmingham, Edgbaston, Birmingham; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (H.R.M.), Cardiff University School of Medicine, Cardiff; Department of Molecular Neuroscience (J.H., N.E.W.), Institute of Neurology, University College London, London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.
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.
UCB pharma
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
David P. Breen, MRCP
From the Wellcome Centre for Mitochondrial Research (G.H., P.F.C.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Laboratory of Neurogenetics (M.N., A.B.S.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical Neurosciences (J.R.E., D.P.B., S.W.-R., C.H.W.-G.), University of Cambridge, Cambridge; Division of Neurosciences (K.E.M., R.A.B.), University of Birmingham, Edgbaston, Birmingham; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (H.R.M.), Cardiff University School of Medicine, Cardiff; Department of Molecular Neuroscience (J.H., N.E.W.), Institute of Neurology, University College London, London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
1. UCB Pharma, speaker fee
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
1. University of Cambridge, Clinical Research Fellow in Neurology 2. Addenbrooke's Hospital NHS Trust, Honorary SpR in Neurology
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.
1. 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
Sophie Winder-Rhodes, BSc
From the Wellcome Centre for Mitochondrial Research (G.H., P.F.C.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Laboratory of Neurogenetics (M.N., A.B.S.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical Neurosciences (J.R.E., D.P.B., S.W.-R., C.H.W.-G.), University of Cambridge, Cambridge; Division of Neurosciences (K.E.M., R.A.B.), University of Birmingham, Edgbaston, Birmingham; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (H.R.M.), Cardiff University School of Medicine, Cardiff; Department of Molecular Neuroscience (J.H., N.E.W.), Institute of Neurology, University College London, London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.
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.
Merck Sharp and Dohme PhD studentship
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
Karen E. Morrison, MD
From the Wellcome Centre for Mitochondrial Research (G.H., P.F.C.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Laboratory of Neurogenetics (M.N., A.B.S.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical Neurosciences (J.R.E., D.P.B., S.W.-R., C.H.W.-G.), University of Cambridge, Cambridge; Division of Neurosciences (K.E.M., R.A.B.), University of Birmingham, Edgbaston, Birmingham; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (H.R.M.), Cardiff University School of Medicine, Cardiff; Department of Molecular Neuroscience (J.H., N.E.W.), Institute of Neurology, University College London, London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Neurodegenerative Disease Management, Editorial Board Member, since 2010.
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, MRCP, PhD
From the Wellcome Centre for Mitochondrial Research (G.H., P.F.C.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Laboratory of Neurogenetics (M.N., A.B.S.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical Neurosciences (J.R.E., D.P.B., S.W.-R., C.H.W.-G.), University of Cambridge, Cambridge; Division of Neurosciences (K.E.M., R.A.B.), University of Birmingham, Edgbaston, Birmingham; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (H.R.M.), Cardiff University School of Medicine, Cardiff; Department of Molecular Neuroscience (J.H., N.E.W.), Institute of Neurology, University College London, London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.
Disclosure
Scientific Advisory Boards:
1.
1) Solvay Panel Member 2009 2) Boerhinger-Ingelheim 2009 3) Solvay 2012
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-
Patents:
1.
C9orf72 expansion and it role in motor neuron disease/ dementia 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-
Research Support, Government Entities:
1.
Welsh Assembly Government - Research Fellowship 2009- 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
Caroline H. Williams-Gray, MCRP, PhD
From the Wellcome Centre for Mitochondrial Research (G.H., P.F.C.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Laboratory of Neurogenetics (M.N., A.B.S.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical Neurosciences (J.R.E., D.P.B., S.W.-R., C.H.W.-G.), University of Cambridge, Cambridge; Division of Neurosciences (K.E.M., R.A.B.), University of Birmingham, Edgbaston, Birmingham; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (H.R.M.), Cardiff University School of Medicine, Cardiff; Department of Molecular Neuroscience (J.H., N.E.W.), Institute of Neurology, University College London, London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Lundbeck, honoraria for speaking engagement
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.
Patrick Berthoud Trust, Clinical Research Fellowship, 2004-2007. Raymond and Beverly Sackler Foundation, Studentship, 2004- 2007.
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
Roger A. Barker, MCRP, PhD
From the Wellcome Centre for Mitochondrial Research (G.H., P.F.C.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Laboratory of Neurogenetics (M.N., A.B.S.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical Neurosciences (J.R.E., D.P.B., S.W.-R., C.H.W.-G.), University of Cambridge, Cambridge; Division of Neurosciences (K.E.M., R.A.B.), University of Birmingham, Edgbaston, Birmingham; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (H.R.M.), Cardiff University School of Medicine, Cardiff; Department of Molecular Neuroscience (J.H., N.E.W.), Institute of Neurology, University College London, London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.
Disclosure
Scientific Advisory Boards:
1.
Teva Lundbeck, UK.
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Teva Lundbeck, Positive steps Meetings 2010, 2011, 2012. MDS Meeting Toronto 2011, Dublin 2012.
Editorial Boards:
1.
Co-Editor in Chief, Journal of Neurology. Editorial Boaard of Journal of Parkinson's Disease; Synapse; Regenerative Medicine.
Patents:
1.
NONE
Publishing Royalties:
1.
Neuroscience at a glance. 5th Edition. 2012.
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.
I have recieved funding from the EU; Parkinson's UK; CHDI; Cure PD; Rosetrees trust; Michael J Fox 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
Andrew B. Singleton, PhD
From the Wellcome Centre for Mitochondrial Research (G.H., P.F.C.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Laboratory of Neurogenetics (M.N., A.B.S.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical Neurosciences (J.R.E., D.P.B., S.W.-R., C.H.W.-G.), University of Cambridge, Cambridge; Division of Neurosciences (K.E.M., R.A.B.), University of Birmingham, Edgbaston, Birmingham; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (H.R.M.), Cardiff University School of Medicine, Cardiff; Department of Molecular Neuroscience (J.H., N.E.W.), Institute of Neurology, University College London, London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
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
John Hardy, MD, PhD
From the Wellcome Centre for Mitochondrial Research (G.H., P.F.C.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Laboratory of Neurogenetics (M.N., A.B.S.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical Neurosciences (J.R.E., D.P.B., S.W.-R., C.H.W.-G.), University of Cambridge, Cambridge; Division of Neurosciences (K.E.M., R.A.B.), University of Birmingham, Edgbaston, Birmingham; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (H.R.M.), Cardiff University School of Medicine, Cardiff; Department of Molecular Neuroscience (J.H., N.E.W.), Institute of Neurology, University College London, London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.
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
Nicholas E. Wood, MD, PhD
From the Wellcome Centre for Mitochondrial Research (G.H., P.F.C.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Laboratory of Neurogenetics (M.N., A.B.S.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical Neurosciences (J.R.E., D.P.B., S.W.-R., C.H.W.-G.), University of Cambridge, Cambridge; Division of Neurosciences (K.E.M., R.A.B.), University of Birmingham, Edgbaston, Birmingham; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (H.R.M.), Cardiff University School of Medicine, Cardiff; Department of Molecular Neuroscience (J.H., N.E.W.), Institute of Neurology, University College London, London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.
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- Journal of PD associate ed 2010- Journal of neurodegenerative disease 2010- Progress in Neurology and Psychiatry 2002-
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
David J. Burn, MD
From the Wellcome Centre for Mitochondrial Research (G.H., P.F.C.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Laboratory of Neurogenetics (M.N., A.B.S.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical Neurosciences (J.R.E., D.P.B., S.W.-R., C.H.W.-G.), University of Cambridge, Cambridge; Division of Neurosciences (K.E.M., R.A.B.), University of Birmingham, Edgbaston, Birmingham; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (H.R.M.), Cardiff University School of Medicine, Cardiff; Department of Molecular Neuroscience (J.H., N.E.W.), Institute of Neurology, University College London, London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Teva-Lundbeck: payment for speaking / chairing annual meetings in 2010-2013 in UK UCB: speaker at national meetings 2010-2013
Editorial Boards:
1.
Movement Disorder Journal: Associate Editor (1st Jan 2010- present)
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
GSK in 2011-2012(payment made to Newcastle University)
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
GSK
Research Support, Government Entities:
1.
Multicentre UK Study of the acetylcholinesterase inhibitor donepezil in early dementia associated with Parkinson's disease (MUSTARDD-PD). NIHR Health Technology Assessment Programme Project REF: 08/14/13: 1st Sept 2010 – 31st Aug 2015; (Burn DJ, Barker RA, Braithwaite B, Burns A, Clarke CE, Hindle JV, Knapp M, Lees AJ, Leroi I, McColl E, McKeith IG, O'Brien JT, Steen IN, Wheatley K). A Biomedical Research Unit in Lewy Body Dementia. NIHR: 1st April 2012 - 31st March 2017; (Burn DJ, McKeith IG, O'Brien JT, Kirkwood TBL, Chinnery PF, Ford GA).
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Parkinson's UK: Visual symptoms in Parkinson's disease and Parkinson's disease dementia: Association with ocular and retinal pathology, visuo-perceptual deficits and impact on daily living and quality of life. Parkinson's UK: November 2007- October 2010; (Archibald N, Mosimann UP, Clarke MP, Burn DJ). Predicting Dementia in Parkinson's disease: A genotypic and phenotypic study (ICICLE-PD). Parkinson's UK REF J0802, UK: October 2007 – September 2012; (Burn DJ, Barker RA, Brooks DJ, O'Brien JT, McKeith IG, Chinnery PF, Owen AM, Brayne CEG, Robbins T, Sawcer S, Coleman S). The Parkinson's Repository of Biomarkers and Networked Datasets (PROBAND) programme: A UK national clinical consortium linking novel biomarker research to clinical expression, and progression rates, in Parkinson's disease. Parkinson's UK: 2011-2015; (Grosset D, Burn DJ, Barker RA, Ben-Shlomo Y, Bajaj N, Hardy J, Wood NW, Morris HR). Apomorphine: A modifier of amyloid deposition in Parkinson's disease? Parkinson's UK REF K-1101: October 2011 - April 2012;(Burn DJ, Revesz T, Lees AJ). Michael J Fox Foundation Clinical trial to compare cognitive scales. Michael J Fox Foundation: 1st October 2011 - 30th September 2016; (Burn DJ, Weintraub D). Predicting cognitive profiles in Parkinson's disease: A multimodal approach. Michael J Fox Foundation: 1st November 2011 - 31st October 2013; (Burn DJ, Rochester L, O'Brien JT, Coleman SY, Baker MR).
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
Patrick F. Chinnery, PhD, FMedSci
From the Wellcome Centre for Mitochondrial Research (G.H., P.F.C.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Laboratory of Neurogenetics (M.N., A.B.S.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical Neurosciences (J.R.E., D.P.B., S.W.-R., C.H.W.-G.), University of Cambridge, Cambridge; Division of Neurosciences (K.E.M., R.A.B.), University of Birmingham, Edgbaston, Birmingham; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics (H.R.M.), Cardiff University School of Medicine, Cardiff; Department of Molecular Neuroscience (J.H., N.E.W.), Institute of Neurology, University College London, London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
BRAIN, Associate Editor 2004
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.
Wellcome 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

Notes

Correspondence to Dr. Chinnery: [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.

Author Contributions

Conceived and designed the experiments: G. Hudson, D. Burn, and P.F. Chinnery. Contributed reagents/materials/analysis tools: G. Hudson, M. Nalls, J.R. Evans, D.P. Breen, S. Winder-Rhodes, K.E. Morrison, H.R. Morris, C.H. Williams-Gray, Wellcome Trust Case Control Consortium 2, R.A. Barker, A.B. Singleton, J. Hardy, N.E. Wood, D.J. Burn, and P.F. Chinnery. Wrote the manuscript: G. Hudson and P.F. Chinnery.

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
  1. A naturally occurring variant of SHLP2 is a protective factor in Parkinson’s disease, Molecular Psychiatry, (2024).https://doi.org/10.1038/s41380-023-02344-0
    Crossref
  2. Quantifying human genome parameters in aging, Vavilov Journal of Genetics and Breeding, 27, 5, (495-501), (2023).https://doi.org/10.18699/VJGB-23-60
    Crossref
  3. Penetrance and expressivity of mitochondrial variants in a large clinically unselected population, Human Molecular Genetics, (2023).https://doi.org/10.1093/hmg/ddad194
    Crossref
  4. The contributions of mitochondrial and nuclear mitochondrial genetic variation to neuroticism, Nature Communications, 14, 1, (2023).https://doi.org/10.1038/s41467-023-38480-y
    Crossref
  5. Insights into the promising prospect of pharmacological approaches targeting mitochondrial dysfunction in major human diseases: At a glance, Process Biochemistry, 132, (41-74), (2023).https://doi.org/10.1016/j.procbio.2023.07.007
    Crossref
  6. North and East African mitochondrial genetic variation needs further characterization towards precision medicine, Journal of Advanced Research, 54, (59-76), (2023).https://doi.org/10.1016/j.jare.2023.01.021
    Crossref
  7. The contribution of mitochondrial DNA alterations to aging, cancer, and neurodegeneration, Experimental Gerontology, 178, (112203), (2023).https://doi.org/10.1016/j.exger.2023.112203
    Crossref
  8. Circulating Mitochondrial DNA and Inter-Organelle Contact Sites in Aging and Associated Conditions, Cells, 11, 4, (675), (2022).https://doi.org/10.3390/cells11040675
    Crossref
  9. Where Does N-Formylmethionine Come from? What for? Where Is It Going?, Molecules and Cells, 45, 3, (109-111), (2022).https://doi.org/10.14348/molcells.2021.5040
    Crossref
  10. Mitochondrial genomic variation in dementia with Lewy bodies: association with disease risk and neuropathological measures, Acta Neuropathologica Communications, 10, 1, (2022).https://doi.org/10.1186/s40478-022-01399-4
    Crossref
  11. See more
Loading...

View Options

Get Access

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

Purchase this article to get full access to it.

Purchase Access, $39 for 24hr of access

View options

Full Text

View Full Text

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

Share

Share

Share article link

Share