Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia, United States of America.
PLoS One. 2014 Dec 26;9(12):e113203. doi: 10.1371/journal.pone.0113203. eCollection 2014.
Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in African Americans.
Up to 8,201 African Americans (including 546 first CHD events) were genotyped using the MetaboChip array in the Atherosclerosis Risk in Communities (ARIC) study and Women's Health Initiative (WHI). We tested associations using Cox proportional hazard models in sex- and study-stratified analyses and combined results using meta-analysis. Among 44 validated CHD loci available in the array, we replicated and fine-mapped the SORT1 locus, and showed same direction of effects as reported in studies of individuals of European ancestry for SNPs in 22 additional published loci. We also identified a SNP achieving array wide significance (MYC: rs2070583, allele frequency 0.02, P = 8.1 × 10(-8)), but the association did not replicate in an additional 8,059 African Americans (577 events) from the WHI, HealthABC and GeneSTAR studies, and in a meta-analysis of 5 cohort studies of European ancestry (24,024 individuals including 1,570 cases of MI and 2,406 cases of CHD) from the CHARGE Consortium.
Our findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans.
冠心病（CHD）是导致非裔美国人发病率和死亡率的主要原因。然而，评估非裔美国人 CHD 遗传决定因素的研究很少。我们研究了 CHD 基因座中已发表的变异与 CHD 发病风险的关联，试图对这些基因座进行精细定位，并确定影响非裔美国人 CHD 风险的新型变异。
多达 8201 名非裔美国人（包括 546 例首次 CHD 事件）在 ARIC 研究和 WHI 中使用 MetaboChip 基因芯片进行了基因分型。我们使用 Cox 比例风险模型在性别和研究分层分析中进行了关联测试，并使用荟萃分析合并了结果。在该基因芯片中可用的 44 个已验证的 CHD 基因座中，我们复制和精细定位了 SORT1 基因座，并显示出与欧洲血统个体研究中报道的相同的效应方向，这与 22 个额外的已发表基因座中的 SNP 一致。我们还发现了一个 SNP 在全基因芯片范围内达到显著水平（MYC：rs2070583，等位基因频率 0.02，P=8.1×10(-8)），但在 WHI、HealthABC 和 GeneSTAR 研究中的另外 8059 名非裔美国人（577 例事件）以及欧洲血统的 5 项队列研究的荟萃分析中（包括 24024 名个体，其中 1570 例 MI 和 2406 例 CHD）中没有发现这种关联。CHARGE 联盟。
我们的研究结果表明，先前在欧洲血统个体中确定的一些 CHD 基因座可能与非裔美国人的 CHD 发病有关。
