BACKGROUND: Genome-wide association studies (GWAS) have identified loci associated with ischemic stroke (IS) and cardiovascular disease (CVD) in European-descent individuals, but their replication in different populations has been largely unexplored. METHODS AND RESULTS: Nine single nucleotide polymorphisms (SNPs) selected from GWAS and meta-analyses of stroke, and 86 SNPs previously associated with myocardial infarction and CVD risk factors, including blood lipids (high density lipoprotein [HDL], low density lipoprotein [LDL], and triglycerides), type 2 diabetes, and body mass index (BMI), were investigated for associations with incident IS in European Americans (EA) N=26 276, African-Americans (AA) N=8970, and American Indians (AI) N=3570 from the Population Architecture using Genomics and Epidemiology Study. Ancestry-specific fixed effects meta-analysis with inverse variance weighting was used to combine study-specific log hazard ratios from Cox proportional hazards models. Two of 9 stroke SNPs (rs783396 and rs1804689) were significantly associated with [corrected] IS hazard in AA; none were significant in this large EA cohort. Of 73 CVD risk factor SNPs tested in EA, 2 (HDL and triglycerides SNPs) were associated with IS. In AA, SNPs associated with LDL, HDL, and BMI were significantly associated with IS (3 of 86 SNPs tested). Out of 58 SNPs tested in AI, 1 LDL SNP was significantly associated with IS. CONCLUSIONS: Our analyses showing lack of replication in spite of reasonable power for many stroke SNPs and differing results by ancestry highlight the need to follow up on GWAS findings and conduct genetic association studies in diverse populations. We found modest IS associations with BMI and lipids SNPs, though these findings require confirmation.
BACKGROUND: Genome-wide association studies (GWAS) have identified loci associated with ischemic stroke (IS) and cardiovascular disease (CVD) in European-descent individuals, but their replication in different populations has been largely unexplored. METHODS AND RESULTS: Nine single nucleotide polymorphisms (SNPs) selected from GWAS and meta-analyses of stroke, and 86 SNPs previously associated with myocardial infarction and CVD risk factors, including blood lipids (high density lipoprotein [HDL], low density lipoprotein [LDL], and triglycerides), type 2 diabetes, and body mass index (BMI), were investigated for associations with incident IS in European Americans (EA) N=26 276, African-Americans (AA) N=8970, and American Indians (AI) N=3570 from the Population Architecture using Genomics and Epidemiology Study. Ancestry-specific fixed effects meta-analysis with inverse variance weighting was used to combine study-specific log hazard ratios from Cox proportional hazards models. Two of 9 stroke SNPs (rs783396 and rs1804689) were significantly associated with [corrected] IS hazard in AA; none were significant in this large EA cohort. Of 73 CVD risk factor SNPs tested in EA, 2 (HDL and triglycerides SNPs) were associated with IS. In AA, SNPs associated with LDL, HDL, and BMI were significantly associated with IS (3 of 86 SNPs tested). Out of 58 SNPs tested in AI, 1 LDL SNP was significantly associated with IS. CONCLUSIONS: Our analyses showing lack of replication in spite of reasonable power for many stroke SNPs and differing results by ancestry highlight the need to follow up on GWAS findings and conduct genetic association studies in diverse populations. We found modest IS associations with BMI and lipids SNPs, though these findings require confirmation.
Authors: E T Lee; T K Welty; R Fabsitz; L D Cowan; N A Le; A J Oopik; A J Cucchiara; P J Savage; B V Howard Journal: Am J Epidemiol Date: 1990-12 Impact factor: 4.897
Authors: L P Fried; N O Borhani; P Enright; C D Furberg; J M Gardin; R A Kronmal; L H Kuller; T A Manolio; M B Mittelmark; A Newman Journal: Ann Epidemiol Date: 1991-02 Impact factor: 3.797
Authors: D G Ives; A L Fitzpatrick; D E Bild; B M Psaty; L H Kuller; P M Crowley; R G Cruise; S Theroux Journal: Ann Epidemiol Date: 1995-07 Impact factor: 3.797
Authors: William S Bush; Jonathan Boston; Sarah A Pendergrass; Logan Dumitrescu; Robert Goodloe; Kristin Brown-Gentry; Sarah Wilson; Bob McClellan; Eric Torstenson; Melissa A Basford; Kylee L Spencer; Marylyn D Ritchie; Dana C Crawford Journal: Pac Symp Biocomput Date: 2013
Authors: Cavin K Ward-Caviness; Paul S de Vries; Kerri L Wiggins; Jennifer E Huffman; Lisa R Yanek; Lawrence F Bielak; Franco Giulianini; Xiuqing Guo; Marcus E Kleber; Tim Kacprowski; Stefan Groß; Astrid Petersman; George Davey Smith; Fernando P Hartwig; Jack Bowden; Gibran Hemani; Martina Müller-Nuraysid; Konstantin Strauch; Wolfgang Koenig; Melanie Waldenberger; Thomas Meitinger; Nathan Pankratz; Eric Boerwinkle; Weihong Tang; Yi-Ping Fu; Andrew D Johnson; Ci Song; Moniek P M de Maat; André G Uitterlinden; Oscar H Franco; Jennifer A Brody; Barbara McKnight; Yii-Der Ida Chen; Bruce M Psaty; Rasika A Mathias; Diane M Becker; Patricia A Peyser; Jennifer A Smith; Suzette J Bielinski; Paul M Ridker; Kent D Taylor; Jie Yao; Russell Tracy; Graciela Delgado; Stella Trompet; Naveed Sattar; J Wouter Jukema; Lewis C Becker; Sharon L R Kardia; Jerome I Rotter; Winfried März; Marcus Dörr; Daniel I Chasman; Abbas Dehghan; Christopher J O'Donnell; Nicholas L Smith; Annette Peters; Alanna C Morrison Journal: PLoS One Date: 2019-05-10 Impact factor: 3.240