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- Title
Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A Meta-Analysis of Genome-Wide Association Studies from the CHARGE Consortium.
- Authors
Lemaitre, Rozenn N.; Tanaka, Toshiko; Weihong Tang; Manichaikul, Ani; Foy, Millennia; Kabagambe, Edmond K.; Nettleton, Jennifer A.; King, Irena B.; Lu-Chen Weng; Bhattacharya, Sayanti; Bandinelli, Stefania; Bis, Joshua C.; Rich, Stephen S.; Jacobs Jr., David R.; Cherubini, Antonio; McKnight, Barbara; Shuang Liang; Xiangjun Gu; Rice, Kenneth; Laurie, Cathy C.
- 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.
- Subjects
PHOSPHOLIPIDS; FATTY acids; LOCUS (Genetics); META-analysis; UNSATURATED fatty acids; LINOLENIC acids; EICOSAPENTAENOIC acid; GLUCOKINASE; COHORT analysis
- Publication
PLoS Genetics, 2011, Vol 7, Issue 7, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1002193