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Genetic determinants of lipid traits in diverse populations from the population architecture using genomics and epidemiology (PAGE) study.

Tuesday,2012-11-06 12:25 America/Los_Angeles — eenright
TitleGenetic determinants of lipid traits in diverse populations from the population architecture using genomics and epidemiology (PAGE) study.
Publication TypeJournal Article
Year of Publication2011
AuthorsDumitrescu, L, Carty, CL, Taylor, K, Schumacher, FR, Hindorff, LA, Ambite, JL, Anderson, G, Best, LG, Brown-Gentry, K, Bůzková, P, Carlson, CS, Cochran, B, Cole, SA, Devereux, RB, Duggan, D, Eaton, CB, Fornage, M, Franceschini, N, Haessler, J, Howard, BV, Johnson, KC, Laston, S, Kolonel, LN, Lee, ET, MacCluer, JW, Manolio, TA, Pendergrass, SA, Quibrera, M, Shohet, RV, Wilkens, LR, Haiman, CA, Le Marchand, L, Buyske, S, Kooperberg, C, North, KE, Crawford, DC
JournalPLoS Genet
Volume7
Issue6
Paginatione1002138
Date Published2011 Jun
ISSN1553-7404
KeywordsAdolescent, Adult, Aged, Aged, 80 and over, Continental Population Groups, Female, Gene Frequency, Genetics, Population, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Lipid Metabolism, Lipoproteins, HDL, Lipoproteins, LDL, Male, Middle Aged, Molecular Epidemiology, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors, Triglycerides, Young Adult
Abstract<p>For the past five years, genome-wide association studies (GWAS) have identified hundreds of common variants associated with human diseases and traits, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. Approximately 95 loci associated with lipid levels have been identified primarily among populations of European ancestry. The Population Architecture using Genomics and Epidemiology (PAGE) study was established in 2008 to characterize GWAS-identified variants in diverse population-based studies. We genotyped 49 GWAS-identified SNPs associated with one or more lipid traits in at least two PAGE studies and across six racial/ethnic groups. We performed a meta-analysis testing for SNP associations with fasting HDL-C, LDL-C, and ln(TG) levels in self-identified European American (~20,000), African American (~9,000), American Indian (~6,000), Mexican American/Hispanic (~2,500), Japanese/East Asian (~690), and Pacific Islander/Native Hawaiian (~175) adults, regardless of lipid-lowering medication use. We replicated 55 of 60 (92%) SNP associations tested in European Americans at p<0.05. Despite sufficient power, we were unable to replicate ABCA1 rs4149268 and rs1883025, CETP rs1864163, and TTC39B rs471364 previously associated with HDL-C and MAFB rs6102059 previously associated with LDL-C. Based on significance (p<0.05) and consistent direction of effect, a majority of replicated genotype-phentoype associations for HDL-C, LDL-C, and ln(TG) in European Americans generalized to African Americans (48%, 61%, and 57%), American Indians (45%, 64%, and 77%), and Mexican Americans/Hispanics (57%, 56%, and 86%). Overall, 16 associations generalized across all three populations. For the associations that did not generalize, differences in effect sizes, allele frequencies, and linkage disequilibrium offer clues to the next generation of association studies for these traits.</p>
DOI10.1371/journal.pgen.1002138
Alternate JournalPLoS Genet.
PubMed ID21738485
PubMed Central IDPMC3128106
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
M01-RR00425 / RR / NCRR NIH HHS / United States
32105-6 / / PHS HHS / United States
N01-HC-45205 / HC / NHLBI NIH HHS / United States
U01 HL041642 / HL / NHLBI NIH HHS / United States
N01-HC-05187 / HC / NHLBI NIH HHS / United States
U01CA98758 / CA / NCI NIH HHS / United States
U01 HL65520 / HL / NHLBI NIH HHS / United States
N01HV48195 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
U01 HL041654 / HL / NHLBI NIH HHS / United States
T32 GM080178 / GM / NIGMS NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
U01 HG004790 / HG / NHGRI NIH HHS / United States
N01-HC-48047 / HC / NHLBI NIH HHS / United States
U01 HL65521 / HL / NHLBI NIH HHS / United States
N01HC48049 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
U01 HG004802 / HG / NHGRI NIH HHS / United States
N01HC45205 / HL / NHLBI NIH HHS / United States
U01 HL41642 / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
42107-26 / / PHS HHS / United States
32115 / / PHS HHS / United States
U01CA136792 / CA / NCI NIH HHS / United States
U01HG004803 / HG / NHGRI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
N01-HC-95095 / HC / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
U01 HL041652 / HL / NHLBI NIH HHS / United States
U01HG004802 / HG / NHGRI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
32100-2 / / PHS HHS / United States
N01-HC-15103 / HC / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
24152 / / PHS HHS / United States
N01-HC-48050 / HC / NHLBI NIH HHS / United States
U01 HL41654 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
42129-32 / / PHS HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01HC95095 / HL / NHLBI NIH HHS / United States
U01 HL41652 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
U01 HG004803 / HG / NHGRI NIH HHS / United States
32118-32119 / / PHS HHS / United States
P01 CA033619 / CA / NCI NIH HHS / United States
N01 -HV-48195 / HV / NHLBI NIH HHS / United States
N01-HC-48049 / HC / NHLBI NIH HHS / United States
U01HG004798 / HG / NHGRI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01 HC045134 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
32108-9 / / PHS HHS / United States
M01 RR000425 / RR / NCRR NIH HHS / United States
N01HC48050 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01HC05187 / HL / NHLBI NIH HHS / United States
U01HG004801 / HG / NHGRI NIH HHS / United States
R37CA54281 / CA / NCI NIH HHS / United States
N01HC48047 / HL / NHLBI NIH HHS / United States
U01 CA098758 / CA / NCI NIH HHS / United States
U01 HL065521 / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
U01HG004790 / HG / NHGRI NIH HHS / United States
U01 HG004798 / HG / NHGRI NIH HHS / United States
U01HL080295 / HL / NHLBI NIH HHS / United States
32122 / / PHS HHS / United States
U01HG004801-01 / HG / NHGRI NIH HHS / United States
N01-HC-48048 / HC / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
44221 / / PHS HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
U01 CA136792 / CA / NCI NIH HHS / United States
32111-13 / / PHS HHS / United States
R37 CA054281 / CA / NCI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
N01WH22110 / WH / WHI NIH HHS / United States
U01 HL065520 / HL / NHLBI NIH HHS / United States
P01CA33619 / CA / NCI NIH HHS / United States
N01HC48048 / HL / NHLBI NIH HHS / United States
R01 CA63 / CA / NCI NIH HHS / United States
U01 HG004801 / HG / NHGRI NIH HHS / United States

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