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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.

Tuesday,2012-11-06 12:25 America/Los_Angeles — eenright
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-derI, 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<p>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.</p>
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
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AG-20098 / AG / NIA NIH HHS / United States
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