Associations Between Incident Ischemic Stroke Events and Stroke and Cardiovascular Disease-Related Genome-Wide Association Studies Single Nucleotide Polymorphisms in the Population Architecture Using Genomics and Epidemiology Study
Year: 2012
Type: review
Study design: Observational Study
Abstract: 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.
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Human Genome Research Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Center for Research Resources
Awards: G1006167785, CARDIA, CLIN CTR FOR THE CLIN TRIAL & OBSERVATIONAL STUDY OF WHI, G1023702118, G1045430581, G1052397333, G10717269, Cardiovascular Disease in Sioux Indians, Women's Health Initiative, G1135917780, Women's Health Initiative, Women's Health Initiative, G118440752, G1220223050, G1241292848, G1243299691, G125972088, CORONARY HEART DISEASE AND STROKE, G1286168924, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, Epidemiology of putative genuine genetic variant: The Women's Health Intiative, Women's Health Initiative, Women's Health Initiative, G136105103, G1462415530, CLIN CTR CLIN TRIAL/OBSERVATIONAL STUDY OF WHI, Women's Health Initiative, G152626716, G1527150935, G153510172, CARDIA, The Strong Heart Study, Phase V, G1548097448, Women's Health Initiative, CORONARY HEART DISEASE AND STROKE, G1623571357, G164614106, CARDIA, G1691174148, G173303992, Women's Health Initiative, Women's Health Initiative, G181468914, Women's Health Initiative, CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84, G191650467, G1941623656, G211028185, Atherosclerosis Risk in Communities Study (ARIC), CLIN CTR CLIN TRIAL/OBSERVATIONAL STUDY OF WHI, Women's Health Initiative, CARDIA-ECHOCARDIOGRAPHY READING, G215333750, G2182082016, G2194386449, CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, Epidemiology of Putative Causal Variants in the Multiethnic Cohort, CARDIA, CCSP FIELD CENTER, CLIN CTR CLIN TRIAL/OBSERVATIONAL STUDY OF WHI, G25881238, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, COMMUNITY AND COHORT SURVEILLANCE PROGRAM, Women's Health Initiative, G270907595, G2768409618, G277826483, G2800149121, CENTRAL HEMOSTATIS LABORATORY FOR CCSP, G2818629771, Strong Heart Family Study, G300426088, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, G3053443584, G305513510, G306350359, LONGITUDINAL STUDIES OF CORONARY HEART DISEASE RISK FACTORS IN YOUNG ADULTS, G3114902838, Cardiovascular Evaluation for the SHS Phase V, CORONARY ARTERY DISEASE RISK DEVELOPMENT IN YOUNG ADULTS, G3191277318, G3226848658, G328935669, G3290335435, Women's Health Initiative, G3337978133, Women's Health Initiative Memory Study (WHIMS), G3404453056, G3410686264, G34347772, G3462919067, Women's Health Initiative, Multiethnic Cohort Study of Diet and Cancer, G3658685098, G3696348274, GWA for Gene-Environment Interaction Effects Influencing CHD, NHLBI DNA Re-sequencing and Genotyping Program -- Genotyping Center, G3916577102, Women's Health Initiative, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, G4002295999, Women's Health Initiative, G4048755144, Women's Health Initiative, NHGRI EpiGenVar Coordinating Center, G413560588, G423252844, Coronary Artery Risk Development in Young Adults (CARDIA) Study - Field Center, G4289235060, COORDINATING CENTER FOR WOMEN'S HEALTH INITIATIVE, G429396632, G4355687608, G445374210, Atherosclerosis Risk in Communities Study (ARIC), Women's Health Initiative, G457330776, Women's Health Initiative, Women's Health Initiative, Women's Health Initiative, G510023084, G5232982263, G5238945333, FOR ALL FIELD CENTER FOR WHI EXTENSION, G528395701, Women's Health Initiative, G5415877130, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, Women's Health Initiative, Epidemiology of Venous Thrombosis and Pulmonary Embolism, G5611709376, G567847597, Atherosclerosis Risk in Communities Study (ARIC), G582705428, Women's Health Initiative, G589878898, G5959015892, G5965015984, CHS Events Follow-up Study, G6226795708, G6424558485, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, G6522987136, G6548750934, CHS-Transition Phase, G6730395537, Women's Health Initiative, Women's Health Initiative, Women's Health Initiative, G6893458194, Women's Health Initiative, G715477388, G7223985928, Women's Health Initiative, G7422186829, Women's Health Initiative, CLIN CTR CLIN TRIAL/OBSERVATIONAL STUDY OF WHI, G7572166205, CHS RETINAL READING CENTER, General Clinical Research Center, G7739768352, Women's Health Initiative, CLINICAL CENTER FOR THE CLINICAL TRIAL & OBSERVATIONAL STUDY OF WHI, G786153652, Genetic Epidemiology of Causal Variants Across the Life Course, Molecular Epidemiology of Nutrition and Cancer in the Multiethnic Cohort Study, G793702358, G7999488110, A Genome-wide Association Study of Prostate Cancer in African Americans, G8226798419, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), G857724489, G8593276544, G8606667874, G863538970, G8898275213, G8913509553, Cardiovascular Disease in Pima Indians, G9000072420, Cancer Center Support Grant, Diabetes Research Center (DRC), From GWAS loci to blood pressure genes, variants & mechanisms - Renewal, G905887895, G936067872, G939135972, Women's Health Initiative, Atherosclerosis Risk in Communities Study (ARIC), G985928507
OpenAlex ID: W2148532613