title: Genome-wide characterization of shared and distinct genetic components that influence blood lipid levels in ethnically diverse human populations.
abstract: Blood lipid concentrations are heritable risk factors associated with atherosclerosis and cardiovascular diseases. Lipid traits exhibit considerable variation among populations of distinct ancestral origin as well as between individuals within a population. We performed association analyses to identify genetic loci influencing lipid concentrations in African American and Hispanic American women in the Women's Health Initiative SNP Health Association Resource. We validated one African-specific high-density lipoprotein cholesterol locus at CD36 as well as 14 known lipid loci that have been previously implicated in studies of European populations. Moreover, we demonstrate striking similarities in genetic architecture (loci influencing the trait, direction and magnitude of genetic effects, and proportions of phenotypic variation explained) of lipid traits across populations. In particular, we found that a disproportionate fraction of lipid variation in African Americans and Hispanic Americans can be attributed to genomic loci exhibiting statistical evidence of association in Europeans, even though the precise genes and variants remain unknown. At the same time, we found substantial allelic heterogeneity within shared loci, characterized both by population-specific rare variants and variants shared among multiple populations that occur at disparate frequencies. The allelic heterogeneity emphasizes the importance of including diverse populations in future genetic association studies of complex traits such as lipids; furthermore, the overlap in lipid loci across populations of diverse ancestral origin argues that additional knowledge can be gleaned from multiple populations.
authors.affiliation: Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Coram
authors.forename: Qing
authors.initials: Q
authors.lastname: Duan
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hoffmann
authors.forename: Timothy
authors.initials: T
authors.lastname: Thornton
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Knowles
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Johnson
authors.forename: Heather M
authors.initials: HM
authors.lastname: Ochs-Balcom
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Donlon
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Martin
authors.forename: Charles B
authors.initials: CB
authors.lastname: Eaton
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Robinson
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Risch
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Alex P
authors.initials: AP
authors.lastname: Reiner
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D002877:Chromosomes, Human; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood*; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D008055:Lipids