• Rozenn N Lemaitre, Toshiko Tanaka, Weihong Tang, Ani Manichaikul, Millennia Foy, Edmond K Kabagambe, Jennifer A Nettleton, Irena B King, Lu-Chen Weng, Sayanti Bhattacharya, Stefania Bandinelli, Joshua C Bis, Stephen S Rich, David R Jacobs, Antonio Cherubini, Barbara McKnight, Shuang Liang, Xiangjun Gu, Kenneth Rice, Cathy C Laurie, Thomas Lumley, Brian L Browning, Bruce M Psaty, Chen Yii-Der I YD, Yechiel Friedlander, Luc Djousse, Jason H Y Wu, David S Siscovick, André G Uitterlinden, Donna K Arnett, Luigi Ferrucci, Myriam Fornage, Michael Y Tsai, Dariush Mozaffarian, and Lyn M Steffen.
• Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States of America. rozenl@u.washington.edu
• PLoS Genet. 2011 Jul 1; 7 (7): e1002193.

AbstractLong-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.

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