Association of Genetic Variants and Incident Coronary Heart Disease in Multiethnic Cohorts
Year: 2011
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Genome-wide association studies identified several single nucleotide polymorphisms (SNP) associated with prevalent coronary heart disease (CHD), but less is known of associations with incident CHD. The association of 13 published CHD SNPs was examined in 5 ancestry groups of 4 large US prospective cohorts. METHODS AND RESULTS: The analyses included incident coronary events over an average 9.1 to 15.7 follow-up person-years in up to 26 617 white individuals (6626 events), 8018 black individuals (914 events), 1903 Hispanic individuals (113 events), 3669 American Indian individuals (595 events), and 885 Asian/Pacific Islander individuals (66 events). We used Cox proportional hazards models (with additive mode of inheritance) adjusted for age, sex, and ancestry (as needed). Nine loci were statistically associated with incident CHD events in white participants: 9p21 (rs10757278; P=4.7 × 10(-41)), 16q23.1 (rs2549513; P=0.0004), 6p24.1 (rs499818; P=0.0002), 2q36.3 (rs2943634; P=6.7 × 10(-6)), MTHFD1L (rs6922269, P=5.1 × 10(-10)), APOE (rs429358; P=2.7×10(-18)), ZNF627 (rs4804611; P=5.0 × 10(-8)), CXCL12 (rs501120; P=1.4 × 10(-6)) and LPL (rs268; P=2.7 × 10(-17)). The 9p21 region showed significant between-study heterogeneity, with larger effects in individuals age 55 years or younger and in women. Inclusion of coronary revascularization procedures among the incident CHD events introduced heterogeneity. The SNPs were not associated with CHD in black participants, and associations varied in other US minorities. CONCLUSIONS: Prospective analyses of white participants replicated several reported cross-sectional CHD-SNP associations.
Authors: Nora Franceschini, Cara Carty, Petra Bůžková, Alex P. Reiner, Tiana Garrett, Yi Lin, Jens-S Vöckler, Lucia A. Hindorff, Shelley A. Cole, Eric Boerwinkle, Dan-Yu Lin, Ebony Bookman, Lyle G. Best, Jonathan N. Bella, Charles Eaton, Philip Greenland, Nancy Jenny, Kari E. North, Darin Taverna, Alicia M. Young, Ewa Deelman, Charles Kooperberg, Bruce Psaty, Gerardo Heiss
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: CARDIA, Cardiovascular Disease in Sioux Indians, G118440752, G1220223050, G1241292848, G1296778726, Epidemiology of putative genuine genetic variant: The Women's Health Intiative, G1325221871, G136105103, G1462415530, CARDIA, The Strong Heart Study, Phase V, CORONARY HEART DISEASE AND STROKE, G1639455850, G164614106, CARDIA, G191650467, G1945424165, G2096661974, Atherosclerosis Risk in Communities Study (ARIC), CARDIA-ECHOCARDIOGRAPHY READING, G215333750, G2194386449, Epidemiology of Putative Causal Variants in the Multiethnic Cohort, CARDIA, CCSP FIELD CENTER, G25881238, COMMUNITY AND COHORT SURVEILLANCE PROGRAM, G2757880588, G277826483, G2786045897, G2800149121, CENTRAL HEMOSTATIS LABORATORY FOR CCSP, Strong Heart Family Study, G2868073770, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, G305513510, LONGITUDINAL STUDIES OF CORONARY HEART DISEASE RISK FACTORS IN YOUNG ADULTS, G3107571658, G3118039104, Cardiovascular Evaluation for the SHS Phase V, CORONARY ARTERY DISEASE RISK DEVELOPMENT IN YOUNG ADULTS, G3191277318, G3226848658, G3236609591, G328935669, G3396487927, G390162502, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, G4048755144, NHGRI EpiGenVar Coordinating Center, G4165892905, G423252844, Coronary Artery Risk Development in Young Adults (CARDIA) Study - Field Center, G4289235060, COORDINATING CENTER FOR WOMEN'S HEALTH INITIATIVE, G443405440, G4484576498, Atherosclerosis Risk in Communities Study (ARIC), G50822097, G510023084, G5232982263, G528395701, G5300833593, G5451084504, G5452216648, Atherosclerosis Risk in Communities Study (ARIC), G582705428, CHS Events Follow-up Study, G6203107232, G6226795708, G6520056932, CHS-Transition Phase, G7053132390, G7112372800, G7133822337, G715477388, CHS RETINAL READING CENTER, General Clinical Research Center, Multidisciplinary Clinical and Translational Science (MCTS) Program (UL1), G786153652, Genetic Epidemiology of Causal Variants Across the Life Course, G793702358, G7999488110, G812579647, G8239625402, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), G8486527673, G8527280383, G8556851140, G8593276544, G8632148071, G863538970, G8750984004, G8907929540, Cardiovascular Disease in Pima Indians, G9000072420, Diabetes Research Center (DRC), G905887895, G939135972, Atherosclerosis Risk in Communities Study (ARIC)
OpenAlex ID: W2168497248