Journal article
Genome-wide characterization of shared and distinct genetic components that influence blood lipid levels in ethnically diverse human populations
American journal of human genetics, Vol.92(6), pp.904-916
06/06/2013
DOI: 10.1016/j.ajhg.2013.04.025
PMCID: PMC3675231
PMID: 23726366
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.
Details
- Title: Subtitle
- Genome-wide characterization of shared and distinct genetic components that influence blood lipid levels in ethnically diverse human populations
- Creators
- Marc A Coram - Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USAQing DuanThomas J HoffmannTimothy ThorntonJoshua W KnowlesNicholas A Johnson - Stanford UniversityHeather M Ochs-BalcomTimothy A DonlonLisa W MartinCharles B EatonJennifer G RobinsonNeil J RischXiaofeng ZhuCharles KooperbergYun LiAlex P ReinerHua Tang
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.92(6), pp.904-916
- Publisher
- United States
- DOI
- 10.1016/j.ajhg.2013.04.025
- PMID
- 23726366
- PMCID
- PMC3675231
- ISSN
- 1537-6605
- eISSN
- 1537-6605
- Grant note
- GM073059 / NIGMS NIH HHS K07 CA136969 / NCI NIH HHS HHSN268201100002I / NHLBI NIH HHS HHSN271201100004C / NIA NIH HHS HHSN268201100001C / WHI NIH HHS P01 GM099568 / NIGMS NIH HHS K01 CA148958 / NCI NIH HHS R25 CA112355 / NCI NIH HHS R01 HG006703 / NHGRI NIH HHS R01 GM073059 / NIGMS NIH HHS HHSN268201100046C / NHLBI NIH HHS HHSN268201100002C / WHI NIH HHS HHSN268201100001I / NHLBI NIH HHS HHSN268201100003C / WHI NIH HHS
- Language
- English
- Date published
- 06/06/2013
- Academic Unit
- Epidemiology; Internal Medicine
- Record Identifier
- 9983995145702771
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