Minority-centric meta-analyses of blood lipid levels identify novel loci in the Population Architecture using Genomics and Epidemiology (PAGE) study

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...

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Bibliographic Details
Published in:PLoS genetics 2020-03, Vol.16 (3), p.e1008684
Main Authors: Hu, Yao, Graff, Mariaelisa, Haessler, Jeffrey, Buyske, Steven, Bien, Stephanie A, Tao, Ran, Highland, Heather M, Nishimura, Katherine K, Zubair, Niha, Lu, Yingchang, Verbanck, Marie, Hilliard, Austin T, Klarin, Derek, Damrauer, Scott M, Ho, Yuk-Lam, Wilson, Peter W F, Chang, Kyong-Mi, Tsao, Philip S, Cho, Kelly, O'Donnell, Christopher J, Assimes, Themistocles L, Petty, Lauren E, Below, Jennifer E, Dikilitas, Ozan, Schaid, Daniel J, Kosel, Matthew L, Kullo, Iftikhar J, Rasmussen-Torvik, Laura J, Jarvik, Gail P, Feng, Qiping, Wei, Wei-Qi, Larson, Eric B, Mentch, Frank D, Almoguera, Berta, Sleiman, Patrick M, Raffield, Laura M, Correa, Adolfo, Martin, Lisa W, Daviglus, Martha, Matise, Tara C, Ambite, Jose Luis, Carlson, Christopher S, Do, Ron, Loos, Ruth J F, Wilkens, Lynne R, Le Marchand, Loic, Haiman, Chris, Stram, Daniel O, Hindorff, Lucia A, North, Kari E, Kooperberg, Charles, Cheng, Iona, Peters, Ulrike
Format: Article
Language:English
Subjects:
African Americans
Analysis
Authorship
Biology and Life Sciences
Cancer
Children & youth
Continental Population Groups - genetics
Databases, Genetic
Diseases
Environmental science
Epidemiology
Europeans
Female
Funding
Gene mapping
Genes
Genetic diversity
Genetic factors
Genetics
Genome-Wide Association Study - methods
Genomes
Genomics
Genotype
Health care policy
Health sciences
Hospitals
Humans
Lipids
Lipids - analysis
Lipids - blood
Lipids - genetics
Male
Medical research
Metabolic disorders
Metagenomics - methods
Minority & ethnic groups
Minority Groups
Multifactorial Inheritance - genetics
Novels
People and Places
Phenotype
Physical Sciences
Polygenic inheritance
Polymorphism, Single Nucleotide - genetics
Population genetics
Population studies
Precision medicine
Preventive medicine
Public health
Research and Analysis Methods
Software
Supervision
Type 2 diabetes
United States - epidemiology
Veterans
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Summary: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.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1008684