Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium |
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Authors: | Lemaitre Rozenn N Tanaka Toshiko Tang Weihong Manichaikul Ani Foy Millennia Kabagambe Edmond K Nettleton Jennifer A King Irena B Weng Lu-Chen Bhattacharya Sayanti Bandinelli Stefania Bis Joshua C Rich Stephen S Jacobs David R Cherubini Antonio McKnight Barbara Liang Shuang Gu Xiangjun Rice Kenneth Laurie Cathy C Lumley Thomas Browning Brian L Psaty Bruce M Chen Yii-Der I Friedlander Yechiel Djousse Luc Wu Jason H Y Siscovick David S Uitterlinden André G Arnett Donna K Ferrucci Luigi Fornage Myriam Tsai Michael Y Mozaffarian Dariush Steffen Lyn M |
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Affiliation: | Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States of America. rozenl@u.washington.edu |
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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. |
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