Advanced

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

Smith, Gustav LU ; Melander, Olle LU ; Lövkvist, Håkan LU ; Hedblad, Bo LU ; Engström, Gunnar LU ; Nilsson, Peter LU ; Carlson, Joyce LU ; Berglund, Göran LU ; Norrving, Bo LU and Lindgren, Arne LU (2009) In Circulation: Cardiovascular Genetics 2(2). p.159-164
Abstract
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 6 common genetic variants on chromosome 9p21, previously associated with coronary artery disease in genome-wide association studies, in 2 population-based studies in southern Sweden, the Lund Stroke Register (n = 1837 cases, 947 controls) and the Malmo Diet and Cancer study (MDC; n = 888 cases, 893 controls). We... (More)
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 6 common genetic variants on chromosome 9p21, previously associated with coronary artery disease in genome-wide association studies, in 2 population-based studies in southern Sweden, the Lund Stroke Register (n = 1837 cases, 947 controls) and the Malmo 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 2 common (minor allele frequencies 0.46 to 0.49) variants, rs2383207 (P = 0.04 in Lund Stroke Register, P = 0.01 in MDC) and rs10757274 (P = 0.03 in Lund Stroke Register, P = 0.03 in MDC), in each sample independently. The strength of the association increased when samples were pooled with an odds ratio of 1.15 (95% CI, 1.05 to 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. (Circ Cardiovasc Genet. 2009; 2: 159-164.) (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
infarction, cerebral, cardiovascular diseases, genetics, atherosclerosis, stroke
in
Circulation: Cardiovascular Genetics
volume
2
issue
2
pages
159 - 164
publisher
American Heart Association
external identifiers
  • wos:000275979200009
  • scopus:70449110469
ISSN
1942-325X
DOI
10.1161/CIRCGENETICS.108.835173
language
English
LU publication?
yes
id
8fc544e1-8b98-417a-8bc8-ab21a3a8ab0d (old id 1586371)
date added to LUP
2010-04-28 07:56:23
date last changed
2017-11-26 03:24:07
@article{8fc544e1-8b98-417a-8bc8-ab21a3a8ab0d,
  abstract     = {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 6 common genetic variants on chromosome 9p21, previously associated with coronary artery disease in genome-wide association studies, in 2 population-based studies in southern Sweden, the Lund Stroke Register (n = 1837 cases, 947 controls) and the Malmo 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 2 common (minor allele frequencies 0.46 to 0.49) variants, rs2383207 (P = 0.04 in Lund Stroke Register, P = 0.01 in MDC) and rs10757274 (P = 0.03 in Lund Stroke Register, P = 0.03 in MDC), in each sample independently. The strength of the association increased when samples were pooled with an odds ratio of 1.15 (95% CI, 1.05 to 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. (Circ Cardiovasc Genet. 2009; 2: 159-164.)},
  author       = {Smith, Gustav and Melander, Olle and Lövkvist, Håkan and Hedblad, Bo and Engström, Gunnar and Nilsson, Peter and Carlson, Joyce and Berglund, Göran and Norrving, Bo and Lindgren, Arne},
  issn         = {1942-325X},
  keyword      = {infarction,cerebral,cardiovascular diseases,genetics,atherosclerosis,stroke},
  language     = {eng},
  number       = {2},
  pages        = {159--164},
  publisher    = {American Heart Association},
  series       = {Circulation: Cardiovascular Genetics},
  title        = {Common Genetic Variants on Chromosome 9p21 Confers Risk of Ischemic Stroke A Large-Scale Genetic Association Study},
  url          = {http://dx.doi.org/10.1161/CIRCGENETICS.108.835173},
  volume       = {2},
  year         = {2009},
}