Multi-ethnic analysis of lipid-associated loci: the NHLBI CARe project.

PLoS One
Authors
Keywords
Abstract

BACKGROUND: Whereas it is well established that plasma lipid levels have substantial heritability within populations, it remains unclear how many of the genetic determinants reported in previous studies (largely performed in European American cohorts) are relevant in different ethnicities.

METHODOLOGY/PRINCIPAL FINDINGS: We tested a set of ∼50,000 polymorphisms from ∼2,000 candidate genes and genetic loci from genome-wide association studies (GWAS) for association with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) in 25,000 European Americans and 9,000 African Americans in the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe). We replicated associations for a number of genes in one or both ethnicities and identified a novel lipid-associated variant in a locus harboring ICAM1. We compared the architecture of genetic loci associated with lipids in both African Americans and European Americans and found that the same genes were relevant across ethnic groups but the specific associated variants at each gene often differed.

CONCLUSIONS/SIGNIFICANCE: We identify or provide further evidence for a number of genetic determinants of plasma lipid levels through population association studies. In many loci the determinants appear to differ substantially between African Americans and European Americans.

Year of Publication
2012
Journal
PLoS One
Volume
7
Issue
5
Pages
e36473
Date Published
2012
ISSN
1932-6203
URL
DOI
10.1371/journal.pone.0036473
PubMed ID
22629316
PubMed Central ID
PMC3357427
Links
Grant list
N01HC55020 / HL / NHLBI NIH HHS / United States
N01-HB-72992 / HB / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
N01-HB-97068 / HB / NHLBI NIH HHS / United States
R01-HL-076784 / HL / NHLBI NIH HHS / United States
N01-HB-97053 / HB / NHLBI NIH HHS / United States
N01-HB-72997 / HB / NHLBI NIH HHS / United States
N01-HB-73003 / HB / NHLBI NIH HHS / United States
N01-HC-45205 / HC / NHLBI NIH HHS / United States
N01-HC-95162 / HC / NHLBI NIH HHS / United States
U01-HL-063429 / HL / NHLBI NIH HHS / United States
N01-HC-05187 / HC / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
U01-HL-053916 / HL / NHLBI NIH HHS / United States
U01 HL053916 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
K99-HL098364 / HL / NHLBI NIH HHS / United States
R01 HL046380 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01-HC-48047 / HC / NHLBI NIH HHS / United States
U01 HL063463 / HL / NHLBI NIH HHS / United States
N01-HB-97064 / HB / NHLBI NIH HHS / United States
N01HC48049 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
N01HC45205 / HL / NHLBI NIH HHS / United States
N01-HC-95163 / HC / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-95168 / HC / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
N01-HB-73002 / HB / NHLBI NIH HHS / United States
N01-HC-45204 / HC / NHLBI NIH HHS / United States
N01-HB-72993 / HB / NHLBI NIH HHS / United States
N01-HB-97070 / HB / NHLBI NIH HHS / United States
N01-HB-97056 / HB / NHLBI NIH HHS / United States
N01-HB-72982 / HB / NHLBI NIH HHS / United States
U01-HL-053934 / HL / NHLBI NIH HHS / United States
N01 HC085085 / HC / NHLBI NIH HHS / United States
N01-HB-73000 / HB / NHLBI NIH HHS / United States
N01-HC-95159 / HC / NHLBI NIH HHS / United States
U01-HL-080295 / HL / NHLBI NIH HHS / United States
R01 HL076784 / HL / NHLBI NIH HHS / United States
N01-HC-95095 / HC / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-95165 / HC / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
U01-HL-077813 / HL / NHLBI NIH HHS / United States
N01-HB-97085 / HB / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
U01-HL-064360 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
U01 HL053938 / HL / NHLBI NIH HHS / United States
R01-AG-028321 / AG / NIA NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
N01-HB-73005 / HB / NHLBI NIH HHS / United States
N01-HC-48050 / HC / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
U01 HL064360 / HL / NHLBI NIH HHS / United States
M01-RR-00080 / RR / NCRR NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
N01-HB-73006 / HB / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC95170 / HL / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
P20 MD006899 / MD / NIMHD NIH HHS / United States
U01 HL077813 / HL / NHLBI NIH HHS / United States
U01-HL-063463 / HL / NHLBI NIH HHS / United States
N01HC95095 / HL / NHLBI NIH HHS / United States
N01-HB-97071 / HB / NHLBI NIH HHS / United States
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N01-HB-97060 / HB / NHLBI NIH HHS / United States
N01-HC-95160 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC65226 / HL / NHLBI NIH HHS / United States
R01-HL-46380 / HL / NHLBI NIH HHS / United States
N01-HC-95171 / HC / NHLBI NIH HHS / United States
U01-HL-053937 / HL / NHLBI NIH HHS / United States
N01-HB-97073 / HB / NHLBI NIH HHS / United States
N01-HB-97054 / HB / NHLBI NIH HHS / United States
K99 HL098364 / HL / NHLBI NIH HHS / United States
U01 HL053934 / HL / NHLBI NIH HHS / United States
U01 HL063429 / HL / NHLBI NIH HHS / United States
N01-HB-72994 / HB / NHLBI NIH HHS / United States
N01 HC085084 / HC / NHLBI NIH HHS / United States
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N01HC75150 / HL / NHLBI NIH HHS / United States
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N01HC95167 / HL / NHLBI NIH HHS / United States
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N01HC25195 / HL / NHLBI NIH HHS / United States
R01 HL071205 / HL / NHLBI NIH HHS / United States
N01-HB-72991 / HB / NHLBI NIH HHS / United States
N01-HB-97072 / HB / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
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N01-HC-95100 / HC / NHLBI NIH HHS / United States
N01HC45204 / HL / NHLBI NIH HHS / United States
N01-HB-97058 / HB / NHLBI NIH HHS / United States
U01-HL-053941 / HL / NHLBI NIH HHS / United States
U01 HL053937 / HL / NHLBI NIH HHS / United States
N01-HC-48048 / HC / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
N01-HB-72996 / HB / NHLBI NIH HHS / United States
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N01HC55021 / HL / NHLBI NIH HHS / United States
R01 AG028321 / AG / NIA NIH HHS / United States
N01-HC-95166 / HC / NHLBI NIH HHS / United States
N01-HB-97061 / HB / NHLBI NIH HHS / United States
U01-HL-053938 / HL / NHLBI NIH HHS / United States
R01-HL-092577 / HL / NHLBI NIH HHS / United States
M01 RR000080 / RR / NCRR NIH HHS / United States
N01-HB-73004 / HB / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
N01-HC-95170 / HC / NHLBI NIH HHS / United States
N01-HB-72998 / HB / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
N01-HB-97069 / HB / NHLBI NIH HHS / United States
N01HC48048 / HL / NHLBI NIH HHS / United States
N01-HC-95167 / HC / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
N01-HC-65226 / HC / NHLBI NIH HHS / United States
N01HC95172 / HL / NHLBI NIH HHS / United States