Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A Meta-Analysis of Genome-Wide Association Studies from the CHARGE Consortium

RN Lemaitre, T Tanaka, WH Tang, A Manichaikul, M Foy, EK Kabagambe, JA Nettleton, IB King, LC Weng, S Bhattacharya, S Bandinelli, JC Bis, SS Rich, DR Jacobs, A Cherubini, B McKnight, S Liang, XJ Gu, K Rice, CC LaurieT Lumley, BL Browning, BM Psaty, YDI Chen, Y Friedlander, L Djousse, JHY Wu, DS Siscovick, André Uitterlinden, DK Arnett, L Ferrucci, M Fornage, MY Tsai, D Mozaffarian, LM Steffen

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Abstract

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from a-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=3x10(-64)) and lower levels of eicosapentaenoic acid (EPA, p=5x10(-58)) and docosapentaenoic acid (DPA, p=4x10(-154)). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p=2x10(-12)) and DPA (p=1x10(-43)) and lower docosahexaenoic acid (DHA, p=1x10(-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=1x10(-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.
Original languageUndefined/Unknown
JournalPLoS Genetics (print)
Volume7
Issue number7
DOIs
Publication statusPublished - 2011

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  • EMC MM-01-39-09-A

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