Human Genetics, GSPH, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
PLoS One. 2013 May 22;8(5):e63469. doi: 10.1371/journal.pone.0063469. Print 2013.
Genome-wide association studies (GWAS) have identified a number of loci/SNPs associated with plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels. The purpose of this study was to replicate 40 recent GWAS-identified HDL-C-related new loci in 3 epidemiological samples comprising U.S. non-Hispanic Whites (NHWs), U.S. Hispanics, and African Blacks. In each sample, the association analyses were performed with all 4 major lipid traits regardless of previously reported specific associations with selected SNPs. A total of 22 SNPs showed nominally significant association (p<0.05) with at least one lipid trait in at least one ethnic group, although not always with the same lipid traits reported as genome-wide significant in the original GWAS. The total number of significant loci was 10 for TC, 12 for LDL-C, 10 for HDL-C, and 6 for TG levels. Ten SNPs were significantly associated with more than one lipid trait in at least one ethnic group. Six SNPs were significantly associated with at least one lipid trait in more than one ethnic group, although not always with the same trait across various ethnic groups. For 25 SNPs, the associations were replicated with the same genome-wide significant lipid traits in the same direction in at least one ethnic group; at nominal significance for 13 SNPs and with a trend for association for 12 SNPs. However, the associations were not consistently present in all ethnic groups. This observation was consistent with mixed results obtained in other studies that also examined various ethnic groups.
全基因组关联研究（GWAS）已经确定了许多与血浆总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）和甘油三酯（TG）水平相关的基因座/单核苷酸多态性（SNP）。本研究的目的是在包含美国非西班牙裔白人（NHW）、美国西班牙裔和非洲黑人的 3 个流行病学样本中复制 40 个最近的与 HDL-C 相关的 GWAS 新基因座。在每个样本中，无论先前是否与特定 SNP 相关联，都对所有 4 种主要脂质特征进行关联分析。共有 22 个 SNP 在至少一个种族群体中与至少一种脂质特征呈显著关联（p<0.05），尽管并非总是与原始 GWAS 中报告的具有全基因组意义的相同脂质特征相关联。TC 有 10 个显著关联的基因座，LDL-C 有 12 个，HDL-C 有 10 个，TG 水平有 6 个。10 个 SNP 在至少一个种族群体中与多种脂质特征显著相关。6 个 SNP 在至少一个以上种族群体中与至少一种脂质特征显著相关，尽管并非总是在不同种族群体中具有相同的特征。对于 25 个 SNP，在至少一个种族群体中，相同的全基因组显著脂质特征以相同的方向具有相同的关联；在 13 个 SNP 中具有名义显著性，在 12 个 SNP 中具有关联趋势。然而，这些关联并不总是存在于所有种族群体中。这种观察结果与其他研究也检查了不同种族群体的混合结果一致。
