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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.

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