Chang Man-huei, Ned Renée M, Hong Yuling, Yesupriya Ajay, Yang Quanhe, Liu Tiebin, Janssens A Cecile J W, Dowling Nicole F
Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Circ Cardiovasc Genet. 2011 Oct;4(5):523-33. doi: 10.1161/CIRCGENETICS.111.959577. Epub 2011 Aug 10.
Genome-wide association studies (GWAS) have identified a number of single-nucleotide polymorphisms (SNPs) associated with serum lipid level in populations of European descent. The individual and the cumulative effect of these SNPs on blood lipids are largely unclear for the US population.
Using data from the second phase (1991-1994) of the Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative survey of the US population, we examined associations of 57 GWAS-identified or well-established lipid-related genetic loci with plasma concentrations of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, total cholesterol, triglycerides, total cholesterol/HDL-C ratio, and non-HDL-C. We used multivariable linear regression to examine single SNP associations and the cumulative effect of multiple SNPs (using a genetic risk score [GRS]) on blood lipid levels. Analyses were conducted in adults from each of the 3 major racial/ethnic groups in the United States: non-Hispanic whites (n=2296), non-Hispanic blacks (n=1699), and Mexican Americans (n=1713). Allele frequencies for all SNPs varied significantly by race/ethnicity, except rs3764261 in CETP. Individual SNPs had very small effects on lipid levels, effects that were generally consistent in direction across racial/ethnic groups. More GWAS-validated SNPs were replicated in non-Hispanic whites (<67%) than in non-Hispanic blacks (<44%) or Mexican Americans (<44%). GRSs were strongly associated with increased lipid levels in each racial/ethnic group. The combination of all SNPs into a weighted GRS explained no more than 11% of the total variance in blood lipid levels.
Our findings show that the combined association of SNPs, based on a GRS, was strongly associated with increased blood lipid measures in all major race/ethnic groups in the United States, which may help in identifying subgroups with a high risk for an unfavorable lipid profile.
全基因组关联研究（GWAS）已在欧洲裔人群中鉴定出一些与血脂水平相关的单核苷酸多态性（SNP）。对于美国人群，这些SNP对血脂的个体及累积效应在很大程度上尚不清楚。
利用第三次全国健康与营养检查调查（NHANES III）第二阶段（1991 - 1994年）的数据，这是一项对美国人群具有全国代表性的调查，我们研究了57个GWAS鉴定的或已明确的与血脂相关的基因位点与血浆高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇、总胆固醇、甘油三酯、总胆固醇/HDL-C比值和非HDL-C浓度之间的关联。我们使用多变量线性回归来研究单个SNP关联以及多个SNP的累积效应（使用遗传风险评分[GRS]）对血脂水平的影响。分析在美国3个主要种族/族裔群体的成年人中进行：非西班牙裔白人（n = 2296）、非西班牙裔黑人（n = 1699）和墨西哥裔美国人（n = 1713）。除CETP中的rs3764261外，所有SNP的等位基因频率在不同种族/族裔间差异显著。单个SNP对血脂水平的影响非常小，且在不同种族/族裔群体中的影响方向通常一致。在非西班牙裔白人（<67%）中比在非西班牙裔黑人（<44%）或墨西哥裔美国人（<44%）中复制出更多经GWAS验证的SNP。GRS与每个种族/族裔群体中血脂水平升高密切相关。将所有SNP组合成加权GRS所解释的血脂水平总方差不超过11%。
我们的研究结果表明，基于GRS的SNP联合关联与美国所有主要种族/族裔群体中血脂测量值升高密切相关，这可能有助于识别血脂谱不良风险高的亚组人群。
