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NEUROLOGY 2009;73:1767-1773
© 2009 American Academy of Neurology

A novel stroke locus identified in a northern Sweden pedigree

Linkage to chromosome 9q31-33 T. Janunger, MSc, S. Nilsson-Ardnor, MD, PhD, P. -G. Wiklund, MD, PhD, P. Lindgren, MStat, S. A. Escher, PhD, K. Lackovic, PhD, A. K. Nilsson, MSc, B. Stegmayr, PhD, K. Asplund, MD, PhD and D. Holmberg, PhD

From the Department of Medical Biosciences, Division of Medical and Clinical Genetics (T.J., S.N.-A., P.L., S.A.E., K.L., A.K.N., D.H.), Department of Public Health and Clinical Medicine, Division of Clinical Medicine (P.-G.W., B.S., K.A.), Umeå University, Sweden; and Center for Infection and Inflammation (D.H.), Copenhagen University Faculty of Life Science, Denmark.

Address correspondence and reprint requests to Dr. Dan Holmberg, Center for Infection and Inflammation, Copenhagen University, Life Science Faculty, DK 1870 Fredriksberg C., Copenhagen, Denmark dan.holmberg{at}life.ku.dk

Objectives: The population of northern Sweden is characterized by reduced genetic diversity and a high incidence of stroke. We sought to reduce genetic variation further, using genealogic analysis in a set of nuclear families affected by stroke, and we subsequently performed a genome-wide scan to identify novel stroke susceptibility loci.

Methods: Through genealogy, 7 nuclear families with a common ancestor, connected over 8 generations, were identified. A genome-wide scan using 449 microsatellite markers was performed with subsequent haplotype analyses.

Results: A maximum allele-sharing lod score of 4.81 on chromosome 9q31-q33 was detected. Haplotype analysis identified a common 2.2-megabase interval in the chromosomal region in 4 of the nuclear families, where an overrepresentation of intracerebral hemorrhage was observed.

Conclusions: We have identified a novel susceptibility locus for stroke. Haplotype analysis suggests that a shared genetic factor is of particular importance for intracerebral hemorrhage.

Abbreviations: Mb = megabase; MONICA = Monitoring of Trends and Determinants of Cardiovascular Diseases; TOAST = Trial of Org 10172 in Acute Stroke Treatment; WHO = World Health Organization.

Supplemental data at www.neurology.org

Supported by grants from The Swedish Stroke Association, the Kempe Foundation, the Swedish Research Council, the Foundation of Strategic Research, and the King Gustaf V and Queen Victoria’s Foundation.

Disclosure: Author disclosures are provided at the end of the article.

Received April 24, 2009. Accepted in final form August 14, 2009.