Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.
Coronary heart disease (CHD) is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C), hypertension, smoking, and type-2 diabetes) in individuals of African ancestry, we performed a genome-wide association study (GWAS) in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD or its risk factors in Caucasians. For five of these regions (CHD: CDKN2A/CDKN2B; HDL-C: FADS1-3, PLTP, LPL, and ABCA1), we could leverage the distinct linkage disequilibrium (LD) patterns in African Americans to identify DNA polymorphisms more strongly associated with the phenotypes than the previously reported index SNPs found in Caucasian populations. We also developed a new approach for association testing in admixed populations that uses allelic and local ancestry variation. Using this method, we discovered several loci that would have been missed using the basic allelic and global ancestry information only. Our conclusions suggest that no major loci uniquely explain the high prevalence of CHD in African Americans. Our project has developed resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia.
Lettre, G; Palmer, CD; Young, T; Ejebe, KG; Allayee, H; Benjamin, EJ; Bennett, F; Bowden, DW; Chakravarti, A; Dreisbach, A; Farlow, DN; Folsom, AR; Fornage, M; Forrester, T; Fox, E; Haiman, CA; Hartiala, J; Harris, TB; Hazen, SL; Heckbert, SR; Henderson, BE; Hirschhorn, JN; Keating, BJ; Kritchevsky, SB; Larkin, E; Li, M; Rudock, ME; McKenzie, CA; Meigs, JB; Meng, YA; Mosley, TH; Newman, AB; Newton-Cheh, CH; Paltoo, DN; Papanicolaou, GJ; Patterson, N; Post, WS; Psaty, BM; Qasim, AN; Qu, L; Rader, DJ; Redline, S; Reilly, MP; Reiner, AP; Rich, SS; Rotter, JI; Liu, Y; Shrader, P; Siscovick, DS; Tang, WHW; Taylor, HA; Tracy, RP; Vasan, RS; Waters, KM; Wilks, R; Wilson, JG; Fabsitz, RR; Gabriel, SB; Kathiresan, S; Boerwinkle, E
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