当前位置: X-MOL 学术PLOS Genet. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Minority-centric meta-analyses of blood lipid levels identify novel loci in the Population Architecture using Genomics and Epidemiology (PAGE) study.
PLOS Genetics ( IF 4.5 ) Pub Date : 2020-03-30 , DOI: 10.1371/journal.pgen.1008684
Yao Hu 1 , Mariaelisa Graff 2 , Jeffrey Haessler 1 , Steven Buyske 3 , Stephanie A Bien 1 , Ran Tao 4, 5 , Heather M Highland 2 , Katherine K Nishimura 1 , Niha Zubair 1 , Yingchang Lu 6 , Marie Verbanck 6 , Austin T Hilliard 7 , Derek Klarin 8, 9, 10 , Scott M Damrauer 11, 12, 13 , Yuk-Lam Ho 14 , , Peter W F Wilson 11, 15 , Kyong-Mi Chang 12, 16 , Philip S Tsao 17, 18 , Kelly Cho 14 , Christopher J O'Donnell 14, 19 , Themistocles L Assimes 17, 18 , Lauren E Petty 5, 20 , Jennifer E Below 5, 20 , Ozan Dikilitas 21 , Daniel J Schaid 22 , Matthew L Kosel 22 , Iftikhar J Kullo 21 , Laura J Rasmussen-Torvik 23 , Gail P Jarvik 24 , Qiping Feng 25 , Wei-Qi Wei 25 , Eric B Larson 26 , Frank D Mentch 27 , Berta Almoguera 27 , Patrick M Sleiman 27 , Laura M Raffield 28 , Adolfo Correa 29 , Lisa W Martin 30 , Martha Daviglus 31, 32 , Tara C Matise 3 , Jose Luis Ambite 33 , Christopher S Carlson 1 , Ron Do 6 , Ruth J F Loos 6 , Lynne R Wilkens 34 , Loic Le Marchand 34 , Chris Haiman 35 , Daniel O Stram 35 , Lucia A Hindorff 36 , Kari E North 2 , Charles Kooperberg 1 , Iona Cheng 37 , Ulrike Peters 1
Affiliation  

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.

中文翻译:

以少数民族为中心的血脂水平荟萃分析使用基因组学和流行病学 (PAGE) 研究确定了人口结构中的新位点。

脂质水平是心脏代谢疾病发展的重要标志。尽管已通过遗传关联研究确定了数百个相关位点,但尚未完全了解遗传因素对脂质变异的贡献,尤其是在美国少数群体中。我们使用基因组学和流行病学 (PAGE) 研究对来自人口结构的 45,000 多名祖先不同的参与者进行了四种脂质特征的全基因组关联分析,然后对几项欧洲血统研究进行了荟萃分析。我们确定了九个新的脂质位点,其中五个在独立研究中显示出复制的证据。此外,我们在 PrediXcan 分析中发现了一个新基因,在先前报道的八个基因座上的少数特定独立信号,以及通过精细定位在两个已知位点的潜在功能变异。对已知脂质位点的系统检查显示,与欧洲人相比,非裔美国人和西班牙裔人群的效应估计值更小,并且基于少数族裔特异性效应估计值的多基因风险评分表现更好。我们的研究结果为脂质性状的遗传结构提供了新的见解,并强调了在精准医学时代对不同人群进行遗传研究的重要性。
更新日期:2020-04-06
down
wechat
bug