Genetic loci associated with plasma phospholipid N-3 fatty acids: A Meta-Analysis of Genome-Wide association studies from the charge consortium

Rozenn N. Lemaitre, Toshiko Tanaka, Weihong Tang, Ani Manichaikul, Millennia Foy, Edmond K. Kabagambe, Jennifer A. Nettleton, Irena B. King, Lu Chen Weng, Sayanti Bhattacharya, Stefania Bandinelli, Joshua C. Bis, Stephen S. Rich, David R. Jacobs, Antonio Cherubini, Barbara McKnight, Shuang Liang, Xiangjun Gu, Kenneth Rice, Cathy C. LaurieThomas Lumley, Brian L. Browning, Bruce M. Psaty, Yii Der I. Chen, Yechiel Friedlander, Luc Djousse, Jason H.Y. Wu, David S. Siscovick, André G. Uitterlinden, Donna K. Arnett, Luigi Ferrucci, Myriam Fornage, Michael Y. Tsai, Dariush Mozaffarian, Lyn M. Steffen

Research output: Contribution to journalArticlepeer-review

211 Scopus citations

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 = 3×10 -64) and lower levels of eicosapentaenoic acid (EPA, p = 5×10 -58) and docosapentaenoic acid (DPA, p = 4×10 -154). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2×10 -12) and DPA (p = 1×10 -43) and lower docosahexaenoic acid (DHA, p = 1×10 -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 = 1×10 -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.

Original languageEnglish (US)
Article numbere1002193
JournalPLoS genetics
Volume7
Issue number7
DOIs
StatePublished - Jul 2011

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