TY - JOUR T1 - Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium. JF - PLoS Genet Y1 - 2011 A1 - Lemaitre, Rozenn N A1 - Tanaka, Toshiko A1 - Tang, Weihong A1 - Manichaikul, Ani A1 - Foy, Millennia A1 - Kabagambe, Edmond K A1 - Nettleton, Jennifer A A1 - King, Irena B A1 - Weng, Lu-Chen A1 - Bhattacharya, Sayanti A1 - Bandinelli, Stefania A1 - Bis, Joshua C A1 - Rich, Stephen S A1 - Jacobs, David R A1 - Cherubini, Antonio A1 - McKnight, Barbara A1 - Liang, Shuang A1 - Gu, Xiangjun A1 - Rice, Kenneth A1 - Laurie, Cathy C A1 - Lumley, Thomas A1 - Browning, Brian L A1 - Psaty, Bruce M A1 - Chen, Yii-der I A1 - Friedlander, Yechiel A1 - Djoussé, Luc A1 - Wu, Jason H Y A1 - Siscovick, David S A1 - Uitterlinden, André G A1 - Arnett, Donna K A1 - Ferrucci, Luigi A1 - Fornage, Myriam A1 - Tsai, Michael Y A1 - Mozaffarian, Dariush A1 - Steffen, Lyn M KW - Alleles KW - Continental Population Groups KW - Fatty Acids, Omega-3 KW - Female KW - Genetic Loci KW - Genome-Wide Association Study KW - Humans KW - Male KW - Metabolic Networks and Pathways KW - Polymorphism, Single Nucleotide AB -

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.

VL - 7 IS - 7 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21829377?dopt=Abstract ER -