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Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.

TitleGenetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.
Publication TypeJournal Article
Year of Publication2011
AuthorsLemaitre RN, Tanaka T, Tang W, Manichaikul A, Foy M, Kabagambe EK, Nettleton JA, King IB, Weng L-C, Bhattacharya S, Bandinelli S, Bis JC, Rich SS, Jacobs DR, Cherubini A, McKnight B, Liang S, Gu X, Rice K, Laurie CC, Lumley T, Browning BL, Psaty BM, Chen Y-DI, Friedlander Y, Djoussé L, H Y Wu J, Siscovick DS, Uitterlinden AG, Arnett DK, Ferrucci L, Fornage M, Tsai MY, Mozaffarian D, Steffen LM
JournalPLoS Genet
Volume7
Issue7
Paginatione1002193
Date Published2011 Jul
ISSN1553-7404
KeywordsAlleles, Continental Population Groups, Fatty Acids, Omega-3, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide
Abstract

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3 x 10⁻⁶⁴) and lower levels of eicosapentaenoic acid (EPA, p = 5 x 10⁻⁵⁸) and docosapentaenoic acid (DPA, p = 4 x 10⁻¹⁵⁴). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2 x 10⁻¹²) and DPA (p = 1 x 10⁻⁴³) and lower docosahexaenoic acid (DHA, p = 1 x 10⁻¹⁵). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1 x 10⁻⁸). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.

DOI10.1371/journal.pgen.1002193
Alternate JournalPLoS Genet
PubMed ID21829377
PubMed Central IDPMC3145614
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
N01-HC-45205 / HC / NHLBI NIH HHS / United States
R01 HL075366 / HL / NHLBI NIH HHS / United States
U01-HG-004446 / HG / NHGRI NIH HHS / United States
N01-HC-05187 / HC / NHLBI NIH HHS / United States
R01 HL071251 / HL / NHLBI NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
HSN268200625226C / / PHS HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
R01 HL071259 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
R01 AG015928 / AG / NIA NIH HHS / United States
R01 HL085710 / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01-HC-48047 / HC / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
R01 HL071252 / HL / NHLBI NIH HHS / United States
N01HC48049 / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HL085251 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
N01HC45205 / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
R01 MD009164 / MD / NIMHD NIH HHS / United States
RR-024156 / RR / NCRR NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
R01 HL085251 / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
263 MD 821336 / MD / NIMHD NIH HHS / United States
R56 AG020098 / AG / NIA NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
N01-HC-45204 / HC / NHLBI NIH HHS / United States
R01 HL071250 / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
UL1 RR024156 / RR / NCRR NIH HHS / United States
N01-HC-95159 / HC / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
AG-20098 / AG / NIA NIH HHS / United States
N01-HC-95095 / HC / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
U01 HG004424 / HG / NHGRI NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
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AG-023269 / AG / NIA NIH HHS / United States
HL075366 / HL / NHLBI NIH HHS / United States
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/ / Intramural NIH HHS / United States
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5K01DK082729-02 / DK / NIDDK NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
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HHSN268201100011C / / PHS HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
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DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
N01HC45204 / HL / NHLBI NIH HHS / United States
K01 DK082729 / DK / NIDDK NIH HHS / United States
R01HL071259 / HL / NHLBI NIH HHS / United States
N01-HC-48048 / HC / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
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R01 HL087641 / HL / NHLBI NIH HHS / United States
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R01 AG027058 / AG / NIA NIH HHS / United States
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