TY - JOUR
T1 - Genetic loci associated with plasma phospholipid N-3 fatty acids
T2 - A Meta-Analysis of Genome-Wide association studies from the charge consortium
AU - Lemaitre, Rozenn N.
AU - Tanaka, Toshiko
AU - Tang, Weihong
AU - Manichaikul, Ani
AU - Foy, Millennia
AU - Kabagambe, Edmond K.
AU - Nettleton, Jennifer A.
AU - King, Irena B.
AU - Weng, Lu Chen
AU - Bhattacharya, Sayanti
AU - Bandinelli, Stefania
AU - Bis, Joshua C.
AU - Rich, Stephen S.
AU - Jacobs, David R.
AU - Cherubini, Antonio
AU - McKnight, Barbara
AU - Liang, Shuang
AU - Gu, Xiangjun
AU - Rice, Kenneth
AU - Laurie, Cathy C.
AU - Lumley, Thomas
AU - Browning, Brian L.
AU - Psaty, Bruce M.
AU - Chen, Yii Der I.
AU - Friedlander, Yechiel
AU - Djousse, Luc
AU - Wu, Jason H.Y.
AU - Siscovick, David S.
AU - Uitterlinden, André G.
AU - Arnett, Donna K.
AU - Ferrucci, Luigi
AU - Fornage, Myriam
AU - Tsai, Michael Y.
AU - Mozaffarian, Dariush
AU - Steffen, Lyn M.
PY - 2011/7
Y1 - 2011/7
N2 - 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.
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 = 3×10 -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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U2 - 10.1371/journal.pgen.1002193
DO - 10.1371/journal.pgen.1002193
M3 - Article
C2 - 21829377
AN - SCOPUS:79960947310
VL - 7
IS - 7
M1 - e1002193
ER -