Published Online
on February 12, 2009

A more recent version of this article appeared on April 1, 2009

This Article Full Text (PDF) All Versions of this Article: 2/2/159    most recent CIRCGENETICS.108.835173v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Smith, J. G. Articles by Lindgren, A. Search for Related Content PubMed Articles by Smith, J. G. Articles by Lindgren, A. Related Collections Clinical genetics Cerebrovascular disease/stroke Acute Cerebral Infarction Genetics of Stroke Risk Factors for Stroke Genetics of cardiovascular disease Related Article

Original Article

Common Genetic Variants on Chromosome 9p21 Confers Risk of Ischemic Stroke: A Large-Scale Genetic Association Study

J. Gustav Smith¹; Olle Melander²; Håkan Lövkvist³; Bo Hedblad²; Gunnar Engström²; Peter Nilsson²; Joyce Carlson³; Göran Berglund²; Bo Norrving³ and Arne Lindgren^3,4

¹ Broad Institute of Harvard and MIT, Cambridge, MA & Lund University, Malmö, Sweden;
² Lund University, Malmö, Sweden;
³ Lund University, Lund, Sweden

⁴ E-mail: arne.lindgren{at}med.lu.se

Background—Epidemiological studies indicate a genetic contribution to ischemic stroke risk but specific genetic variants remain unknown with the exception of a few rare variants. Recent genome-wide association studies identified and replicated common genetic variants on chromosome 9p21 to confer risk of coronary heart disease. We examined whether these variants are associated with ischemic stroke.

Methods and Results—We genotyped six common genetic variants on chromosome 9p21, previously associated with coronary artery disease in genome-wide association studies, in two population-based studies in southern Sweden; Lund Stroke Register (LSR, n=1837 cases, 947 controls) and Malmö Diet and Cancer study (MDC, n=888 cases, 893 controls). We examined association in each study and in the pooled dataset. Adjustments were made for cardiovascular risk factors and further for previous myocardial infarction in MDC.

We found a modest increase in ischemic stroke risk for two common (minor allele frequencies 0.46-0.49) variants, rs2383207 (p=0.04 in LSR, p=0.01 in MDC) and rs10757274 (p=0.03 in LSR, p=0.03 in MDC), in each sample independently. The strength of the association increased when samples were pooled with an OR of 1.15 (95%CI=1.05-1.25, p=0.002) for the strongest variant rs2383207. Results were similar after adjustment for clinical covariates. rs1333049 also showed significant association in MDC which increased in the pooled sample (p=0.004).

Conclusions—In this large sample (n=4565) we detected common genetic determinants for ischemic stroke on chromosome 9p21. Our findings indicate that ischemic stroke shares pathophysiological determinants with coronary heart disease and other arterial diseases and highlight the need for large sample sizes in stroke genetics.

Key Words: atherosclerosis • cardiovascular diseases • cerebral infarction • genetics

Related Article

Common Genetic Variants on Chromosome 9p21 Confers Risk of Ischemic Stroke: A Large-Scale Genetic Association Study

J. Gustav Smith, Olle Melander, Håkan Lövkvist, Bo Hedblad, Gunnar Engström, Peter Nilsson, Joyce Carlson, Göran Berglund, Bo Norrving, and Arne Lindgren
Circ Cardiovasc Genet 2009 2: 159-164. [Abstract] [Full Text] [PDF]