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首页> 外文期刊>PLoS Genetics >Minority-centric meta-analyses of blood lipid levels identify novel loci in the Population Architecture using Genomics and Epidemiology (PAGE) study
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Minority-centric meta-analyses of blood lipid levels identify novel loci in the Population Architecture using Genomics and Epidemiology (PAGE) study

机译：血脂水平以少数族裔的荟萃分析使用基因组学和流行病学（页面）研究识别人口架构中的新型基因座

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Lipid levels are important markers for the development of cardio-metabolic diseases. Although hundreds of associated loci have been identified through genetic association studies, the contribution of genetic factors to variation in lipids is not fully understood, particularly in U.S. minority groups. We performed genome-wide association analyses for four lipid traits in over 45,000 ancestrally diverse participants from the Population Architecture using Genomics and Epidemiology (PAGE) Study, followed by a meta-analysis with several European ancestry studies. We identified nine novel lipid loci, five of which showed evidence of replication in independent studies. Furthermore, we discovered one novel gene in a PrediXcan analysis, minority-specific independent signals at eight previously reported loci, and potential functional variants at two known loci through fine-mapping. Systematic examination of known lipid loci revealed smaller effect estimates in African American and Hispanic ancestry populations than those in Europeans, and better performance of polygenic risk scores based on minority-specific effect estimates. Our findings provide new insight into the genetic architecture of lipid traits and highlight the importance of conducting genetic studies in diverse populations in the era of precision medicine.
机译：脂质水平是有氧代谢疾病发展的重要标志。尽管通过遗传关联研究已经确定了数百个相关的基因座，但遗传因素对脂质变异的贡献尚未完全理解，特别是在美国少数群体中。我们使用基因组和流行病学（页面）研究，对超过45,000名血统各种参与者进行全基因组关联分析，从人口架构（页面）研究，随后与几个欧洲祖先研究进行了荟萃分析。我们确定了九个新型脂质基因座，其中五个是在独立研究中显示复制的证据。此外，我们发现了一种新的PREIXCAN分析中的一种新基因，在八个先前报告的基因座的少数特异性独立信号中，以及通过微映射的两个已知基因座的潜在功能变体。已知的脂质基因座的系统检验显示非洲裔美国人和西班牙裔祖先人群的较小效果估计，而不是欧洲人的血统，以及基于少数群体特定效应估计的多种子规范成绩更好地表现。我们的调查结果为脂质特征的遗传建筑提供了新的洞察力，并突出了在精密药中各种群体中进行遗传研究的重要性。

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