@article{2bf740e8d3ea4e81af23593f2e2a4241,
title = "Minority-centric meta-analyses of blood lipid levels identify novel loci in the Population Architecture using Genomics and Epidemiology (PAGE) study",
abstract = "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.",
author = "{VA Million Veteran Program} and Yao Hu and Mariaelisa Graff and Jeffrey Haessler and Steven Buyske and Bien, {Stephanie A.} and Ran Tao and Highland, {Heather M.} and Nishimura, {Katherine K.} and Niha Zubair and Yingchang Lu and Marie Verbanck and Hilliard, {Austin T.} and Derek Klarin and Damrauer, {Scott M.} and Ho, {Yuk Lam} and Wilson, {Peter W.F.} and Chang, {Kyong Mi} and Tsao, {Philip S.} and Kelly Cho and O'Donnell, {Christopher J.} and Assimes, {Themistocles L.} and Petty, {Lauren E.} and Below, {Jennifer E.} and Ozan Dikilitas and Schaid, {Daniel J.} and Kosel, {Matthew L.} and Kullo, {Iftikhar J.} and Rasmussen-Torvik, {Laura J.} and Jarvik, {Gail P.} and Qiping Feng and Wei, {Wei Qi} and Larson, {Eric B.} and Mentch, {Frank D.} and Berta Almoguera and Sleiman, {Patrick M.} and Raffield, {Laura M.} and Adolfo Correa and Martin, {Lisa W.} and Martha Daviglus and Matise, {Tara C.} and Ambite, {Jose Luis} and Carlson, {Christopher S.} and Ron Do and Loos, {Ruth J.F.} and Wilkens, {Lynne R.} and {Le Marchand}, Loic and Chris Haiman and Stram, {Daniel O.} and Hindorff, {Lucia A.} and North, {Kari E.}",
note = "Publisher Copyright: {\textcopyright} This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.",
year = "2020",
month = mar,
day = "1",
doi = "10.1371/journal.pgen.1008684",
language = "English (US)",
volume = "16",
journal = "PLoS genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "3",
}