title: Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.
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.
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States of America. rozenl@u.washington.edu
authors.forename: Rozenn N
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authors.lastname: Psaty
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authors.lastname: Chen
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authors.lastname: Friedlander
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authors.lastname: Djousse
authors.forename: Jason H Y
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authors.lastname: Wu
authors.forename: David S
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authors.lastname: Siscovick
authors.forename: André G
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authors.lastname: Uitterlinden
authors.forename: Donna K
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authors.lastname: Arnett
authors.forename: Luigi
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authors.lastname: Ferrucci
authors.forename: Myriam
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authors.lastname: Fornage
authors.forename: Michael Y
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authors.lastname: Tsai
authors.forename: Dariush
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authors.lastname: Mozaffarian
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mesh_terms: D000483:Alleles; D000090943:Delta-5 Fatty Acid Desaturase; D015525:Fatty Acids, Omega-3 / Q000097:blood*; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044469:Racial Groups / Q000235:genetics
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D015525:Fatty Acids, Omega-3; C000716847:FADS1 protein, human