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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.


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.

SUBMITTER: Hu Y 

PROVIDER: S-EPMC7145272 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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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.

Hu Yao Y   Graff Mariaelisa M   Haessler Jeffrey J   Buyske Steven S   Bien Stephanie A SA   Tao Ran R   Highland Heather M HM   Nishimura Katherine K KK   Zubair Niha N   Lu Yingchang Y   Verbanck Marie M   Hilliard Austin T AT   Klarin Derek D   Damrauer Scott M SM   Ho Yuk-Lam YL   Wilson Peter W F PWF   Chang Kyong-Mi KM   Tsao Philip S PS   Cho Kelly K   O'Donnell Christopher J CJ   Assimes Themistocles L TL   Petty Lauren E LE   Below Jennifer E JE   Dikilitas Ozan O   Schaid Daniel J DJ   Kosel Matthew L ML   Kullo Iftikhar J IJ   Rasmussen-Torvik Laura J LJ   Jarvik Gail P GP   Feng Qiping Q   Wei Wei-Qi WQ   Larson Eric B EB   Mentch Frank D FD   Almoguera Berta B   Sleiman Patrick M PM   Raffield Laura M LM   Correa Adolfo A   Martin Lisa W LW   Daviglus Martha M   Matise Tara C TC   Ambite Jose Luis JL   Carlson Christopher S CS   Do Ron R   Loos Ruth J F RJF   Wilkens Lynne R LR   Le Marchand Loic L   Haiman Chris C   Stram Daniel O DO   Hindorff Lucia A LA   North Kari E KE   Kooperberg Charles C   Cheng Iona I   Peters Ulrike U  

PLoS genetics 20200330 3


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, fol  ...[more]

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