Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
Nat Genet. 2013 Nov;45(11):1274-1283. doi: 10.1038/ng.2797. Epub 2013 Oct 6.
Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
低密度脂蛋白（LDL）胆固醇、高密度脂蛋白（HDL）胆固醇、甘油三酯和总胆固醇水平是冠心病的遗传可修饰危险因素。为了确定影响这些脂质的新基因座和改进已知基因座，我们使用全基因组和定制基因分型阵列检查了 188577 个人。我们在 P < 5 × 10(-8) 水平下鉴定和注释了与脂质水平相关的 157 个基因座，其中包括 62 个以前与人类脂质水平无关的基因座。使用欧洲、东亚、南亚和非裔个体的密集基因分型，我们在 12 个基因座中缩小了关联信号。我们发现与血液脂质水平相关的基因座通常与心血管和代谢特征相关，包括冠心病、2 型糖尿病、血压、腰臀比和体重指数。我们的研究结果证明了利用具有不同祖先的个体的遗传数据的价值，并为调节血液脂质的生物学机制提供了新的见解，以指导未来的遗传、生物学和治疗研究。
