OBJECTIVE: Recent studies have identified a major locus for risk for coronary artery disease and myocardial infarction on chromosome 9p21.3. Stroke, in particular, ischemic stroke caused by atherosclerotic disease, shares common mechanisms with myocardial infarction. We investigated whether the 9p21 region contributes to ischemic stroke risk. METHODS: In an initial screen, 15 single nucleotide polymorphisms (SNPs) covering the critical genetic interval on 9p21 were genotyped in samples from Southern Germany (1,090 cases, 1,244 control subjects) and the United Kingdom (758 cases, 872 control subjects, 3 SNPs). SNPs significantly associated with ischemic stroke or individual stroke subtypes in either of the screening samples were subsequently genotyped in 2,528 additional cases and 2,189 additional control subjects from Europe and North America. RESULTS: Genotyping of the screening samples demonstrated associations between seven SNPs and atherosclerotic stroke (all p < 0.05). Analysis of the full sample confirmed associations between six SNPs and atherosclerotic stroke in multivariate analyses controlling for demographic variables, coronary artery disease, myocardial infarction, and vascular risk factors (all p < 0.05). The odds ratios for the lead SNP (rs1537378-C) were similar in the various subsamples with a pooled odds ratio of 1.21 (95% confidence interval, 1.07-1.37) under both fixed- and random-effects models (p = 0.002). The point estimate for the population attributable risk is 20.1% for atherosclerotic stroke. INTERPRETATION: The chromosome 9p21.3 region represents a major risk locus for atherosclerotic stroke. The effect of this locus on stroke appears to be independent of its relation to coronary artery disease and other stroke risk factors. Our findings support a broad role of the 9p21 region in arterial disease.
OBJECTIVE: Recent studies have identified a major locus for risk for coronary artery disease and myocardial infarction on chromosome 9p21.3. Stroke, in particular, ischemic stroke caused by atherosclerotic disease, shares common mechanisms with myocardial infarction. We investigated whether the 9p21 region contributes to ischemic stroke risk. METHODS: In an initial screen, 15 single nucleotide polymorphisms (SNPs) covering the critical genetic interval on 9p21 were genotyped in samples from Southern Germany (1,090 cases, 1,244 control subjects) and the United Kingdom (758 cases, 872 control subjects, 3 SNPs). SNPs significantly associated with ischemic stroke or individual stroke subtypes in either of the screening samples were subsequently genotyped in 2,528 additional cases and 2,189 additional control subjects from Europe and North America. RESULTS: Genotyping of the screening samples demonstrated associations between seven SNPs and atherosclerotic stroke (all p < 0.05). Analysis of the full sample confirmed associations between six SNPs and atherosclerotic stroke in multivariate analyses controlling for demographic variables, coronary artery disease, myocardial infarction, and vascular risk factors (all p < 0.05). The odds ratios for the lead SNP (rs1537378-C) were similar in the various subsamples with a pooled odds ratio of 1.21 (95% confidence interval, 1.07-1.37) under both fixed- and random-effects models (p = 0.002). The point estimate for the population attributable risk is 20.1% for atherosclerotic stroke. INTERPRETATION: The chromosome 9p21.3 region represents a major risk locus for atherosclerotic stroke. The effect of this locus on stroke appears to be independent of its relation to coronary artery disease and other stroke risk factors. Our findings support a broad role of the 9p21 region in arterial disease.
Authors: Richard C Pasternak; Michael H Criqui; Emelia J Benjamin; F Gerald R Fowkes; Eric M Isselbacher; Peter A McCullough; Philip A Wolf; Zhi-Jie Zheng Journal: Circulation Date: 2004-06-01 Impact factor: 29.690
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Authors: James F Meschia; Donna K Arnett; Hakan Ay; Robert D Brown; Oscar R Benavente; John W Cole; Paul I W de Bakker; Martin Dichgans; Kimberly F Doheny; Myriam Fornage; Raji P Grewal; Katrina Gwinn; Christina Jern; Jordi Jimenez Conde; Julie A Johnson; Katarina Jood; Cathy C Laurie; Jin-Moo Lee; Arne Lindgren; Hugh S Markus; Patrick F McArdle; Leslie A McClure; Braxton D Mitchell; Reinhold Schmidt; Kathryn M Rexrode; Stephen S Rich; Jonathan Rosand; Peter M Rothwell; Tatjana Rundek; Ralph L Sacco; Pankaj Sharma; Alan R Shuldiner; Agnieszka Slowik; Sylvia Wassertheil-Smoller; Cathie Sudlow; Vincent N S Thijs; Daniel Woo; Bradford B Worrall; Ona Wu; Steven J Kittner Journal: Stroke Date: 2013-09-10 Impact factor: 7.914
Authors: Rainer Malik; Therese Dau; Maria Gonik; Anirudh Sivakumar; Daniel J Deredge; Evgeniia V Edeleva; Jessica Götzfried; Sander W van der Laan; Gerard Pasterkamp; Nathalie Beaufort; Susana Seixas; Steve Bevan; Lisa F Lincz; Elizabeth G Holliday; Annette I Burgess; Kristiina Rannikmäe; Jens Minnerup; Jennifer Kriebel; Melanie Waldenberger; Martina Müller-Nurasyid; Peter Lichtner; Danish Saleheen; Peter M Rothwell; Christopher Levi; John Attia; Cathie L M Sudlow; Dieter Braun; Hugh S Markus; Patrick L Wintrode; Klaus Berger; Dieter E Jenne; Martin Dichgans Journal: Proc Natl Acad Sci U S A Date: 2017-03-06 Impact factor: 11.205