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Post-genome-wide association study challenges for lipid traits: describing age as a modifier of gene-lipid associations in the Population Architecture using Genomics and Epidemiology (PAGE) study.

Wednesday,2013-10-16 13:16 America/Los_Angeles — eenright
TitlePost-genome-wide association study challenges for lipid traits: describing age as a modifier of gene-lipid associations in the Population Architecture using Genomics and Epidemiology (PAGE) study.
Publication TypeJournal Article
Year of Publication2013
AuthorsDumitrescu, L, Carty, CL, Franceschini, N, Hindorff, LA, Cole, SA, Bůzková, P, Schumacher, FR, Eaton, CB, Goodloe, RJ, Duggan, DJ, Haessler, J, Cochran, B, Henderson, BE, Cheng, I, Johnson, KC, Carlson, CS, Love, S-A, Brown-Gentry, K, Nato, AQ, Quibrera, M, Anderson, G, Shohet, RV, Ambite, JLuis, Wilkens, LR, Le Marchand, L, Haiman, CA, Buyske, S, Kooperberg, C, North, KE, Fornage, M, Crawford, DC
JournalAnn Hum Genet
Volume77
Issue5
Pagination416-25
Date Published2013 Sep
ISSN1469-1809
KeywordsAdult, Aged, European Continental Ancestry Group, Female, Genetic Association Studies, Genome-Wide Association Study, Humans, Lipids, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Risk Factors
Abstract<p>Numerous common genetic variants that influence plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride distributions have been identified via genome-wide association studies (GWAS). However, whether or not these associations are age-dependent has largely been overlooked. We conducted an association study and meta-analysis in more than 22,000 European Americans between 49 previously identified GWAS variants and the three lipid traits, stratified by age (males: <50 or ≥50 years of age; females: pre- or postmenopausal). For each variant, a test of heterogeneity was performed between the two age strata and significant Phet values were used as evidence of age-specific genetic effects. We identified seven associations in females and eight in males that displayed suggestive heterogeneity by age (Phet < 0.05). The association between rs174547 (FADS1) and LDL-C in males displayed the most evidence for heterogeneity between age groups (Phet = 1.74E-03, I(2) = 89.8), with a significant association in older males (P = 1.39E-06) but not younger males (P = 0.99). However, none of the suggestive modifying effects survived adjustment for multiple testing, highlighting the challenges of identifying modifiers of modest SNP-trait associations despite large sample sizes. </p>
DOI10.1111/ahg.12027
Alternate JournalAnn. Hum. Genet.
PubMed ID23808484
PubMed Central IDPMC3796061
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
32105-6 / / PHS HHS / United States
N01-HC-45205 / HC / NHLBI NIH HHS / United States
N01-HC-05187 / HC / NHLBI NIH HHS / United States
U01CA98758 / CA / NCI NIH HHS / United States
N01HV48195 / HL / NHLBI NIH HHS / United States
N01-HV-48195 / HV / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
T32 GM080178 / GM / NIGMS NIH HHS / United States
R01 AG015928 / AG / NIA 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
85079 / / PHS 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
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01 HC055018 / HC / NHLBI NIH HHS / United States
42107-26 / / PHS HHS / United States
R56 AG020098 / AG / NIA NIH HHS / United States
32115 / / PHS HHS / United States
N01 WH022110 / WH / WHI NIH HHS / United States
U01CA136792 / CA / NCI NIH HHS / United States
U01HG004803 / HG / NHGRI NIH HHS / United States
AG-20098 / AG / NIA 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
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
N01HC85086 / HL / NHLBI NIH HHS / United States
24152 / / PHS HHS / United States
N01-HC-48050 / HC / NHLBI NIH HHS / United States
AG-027058 / AG / NIA 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
HHSN268201200036C / HL / NHLBI NIH HHS / United States
N01HC95095 / 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 HC045204 / HC / NHLBI NIH HHS / United States
N01-HC-48049 / HC / NHLBI NIH HHS / United States
U01HG004798-01 / HG / NHGRI 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
N01-HC / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
32108-9 / / PHS HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
R01 AG020098 / AG / NIA 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
HHSN268201200036C / / PHS HHS / United States
U01HG004790 / HG / NHGRI NIH HHS / United States
U01 HG004798 / HG / NHGRI NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
32122 / / PHS HHS / United States
U01HG004801-01 / HG / NHGRI NIH HHS / United States
N01 WH022110-024 / WH / WHI NIH HHS / United States
N01-HC-85239 / HC / NHLBI NIH HHS / United States
N01-HC-48048 / HC / NHLBI NIH HHS / United States
AG-023629 / AG / NIA 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
R01 AG023629 / AG / NIA NIH HHS / United States
44221 / / PHS HHS / United States
R01 AG027058 / AG / NIA NIH 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
R56 AG023629 / AG / NIA NIH HHS / United States
N01WH22110 / WH / WHI 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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