03576nas a2200673 4500008004100000022001400041245014900055210006900204260001300273300001300286490000600299520159100305653001201896653003401908653002501942653001101967653001701978653003401995653001102029653000902040653003602049653003602085100002402121700002002145700001802165700002102183700001902204700002502223700002702248700001902275700001802294700002602312700002502338700001902363700002102382700002102403700002302424700002202447700001802469700001702487700001802504700002102522700001902543700002302562700002002585700002102605700002502626700001802651700001802669700002402687700002802711700002102739700002002760700002002780700002102800700002502821700002002846856003602866 2011 eng d a1553-740400aGenetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.0 aGenetic loci associated with plasma phospholipid n3 fatty acids c2011 Jul ae10021930 v73 a
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.
10aAlleles10aContinental Population Groups10aFatty Acids, Omega-310aFemale10aGenetic Loci10aGenome-Wide Association Study10aHumans10aMale10aMetabolic Networks and Pathways10aPolymorphism, Single Nucleotide1 aLemaitre, Rozenn, N1 aTanaka, Toshiko1 aTang, Weihong1 aManichaikul, Ani1 aFoy, Millennia1 aKabagambe, Edmond, K1 aNettleton, Jennifer, A1 aKing, Irena, B1 aWeng, Lu-Chen1 aBhattacharya, Sayanti1 aBandinelli, Stefania1 aBis, Joshua, C1 aRich, Stephen, S1 aJacobs, David, R1 aCherubini, Antonio1 aMcKnight, Barbara1 aLiang, Shuang1 aGu, Xiangjun1 aRice, Kenneth1 aLaurie, Cathy, C1 aLumley, Thomas1 aBrowning, Brian, L1 aPsaty, Bruce, M1 aChen, Yii-der, I1 aFriedlander, Yechiel1 aDjoussé, Luc1 aH Y Wu, Jason1 aSiscovick, David, S1 aUitterlinden, André, G1 aArnett, Donna, K1 aFerrucci, Luigi1 aFornage, Myriam1 aTsai, Michael, Y1 aMozaffarian, Dariush1 aSteffen, Lyn, M uhttps://chs-nhlbi.org/node/1311