03759nas a2200649 4500008004100000022001400041245015900055210006900214260001300283300001200296490000600308520187100314653001002185653000902195653002202204653001002226653003202236653003202268653003102300653002702331653002502358653001102383653003402394653001302428653001902441653001102460653000902471653001602480653003602496653002402532653002702556100001702583700002202600700002402622700001802646700002002664700002102684700001902705700002102724700001302745700002702758700001802785700001702803700002502820700001902845700002202864700002002886700002102906700001802927700002202945700002002967700002002987700002503007700002103032700002003053856003603073 2014 eng d a1942-326800aGenome-wide association study of plasma N6 polyunsaturated fatty acids within the cohorts for heart and aging research in genomic epidemiology consortium.0 aGenomewide association study of plasma N6 polyunsaturated fatty c2014 Jun a321-3310 v73 a
BACKGROUND: Omega6 (n6) polyunsaturated fatty acids (PUFAs) and their metabolites are involved in cell signaling, inflammation, clot formation, and other crucial biological processes. Genetic components, such as variants of fatty acid desaturase (FADS) genes, determine the composition of n6 PUFAs.
METHODS AND RESULTS: To elucidate undiscovered biological pathways that may influence n6 PUFA composition, we conducted genome-wide association studies and meta-analyses of associations of common genetic variants with 6 plasma n6 PUFAs in 8631 white adults (55% women) across 5 prospective studies. Plasma phospholipid or total plasma fatty acids were analyzed by similar gas chromatography techniques. The n6 fatty acids linoleic acid (LA), γ-linolenic acid (GLA), dihomo-GLA, arachidonic acid, and adrenic acid were expressed as percentage of total fatty acids. We performed linear regression with robust SEs to test for single-nucleotide polymorphism-fatty acid associations, with pooling using inverse-variance-weighted meta-analysis. Novel regions were identified on chromosome 10 associated with LA (rs10740118; P=8.1×10(-9); near NRBF2), on chromosome 16 with LA, GLA, dihomo-GLA, and arachidonic acid (rs16966952; P=1.2×10(-15), 5.0×10(-11), 7.6×10(-65), and 2.4×10(-10), respectively; NTAN1), and on chromosome 6 with adrenic acid after adjustment for arachidonic acid (rs3134950; P=2.1×10(-10); AGPAT1). We confirmed previous findings of the FADS cluster on chromosome 11 with LA and arachidonic acid, and further observed novel genome-wide significant association of this cluster with GLA, dihomo-GLA, and adrenic acid (P=2.3×10(-72), 2.6×10(-151), and 6.3×10(-140), respectively).
CONCLUSIONS: Our findings suggest that along with the FADS gene cluster, additional genes may influence n6 PUFA composition.
10aAdult10aAged10aAged, 80 and over10aAging10aChromosomes, Human, Pair 1010aChromosomes, Human, Pair 1610aChromosomes, Human, Pair 610aFatty Acid Desaturases10aFatty Acids, Omega-610aFemale10aGenome-Wide Association Study10aGenomics10aHeart Diseases10aHumans10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide10aProspective Studies10aSequence Analysis, DNA1 aGuan, Weihua1 aSteffen, Brian, T1 aLemaitre, Rozenn, N1 aH Y Wu, Jason1 aTanaka, Toshiko1 aManichaikul, Ani1 aFoy, Millennia1 aRich, Stephen, S1 aWang, Lu1 aNettleton, Jennifer, A1 aTang, Weihong1 aGu, Xiangjun1 aBandinelli, Stafania1 aKing, Irena, B1 aMcKnight, Barbara1 aPsaty, Bruce, M1 aSiscovick, David1 aDjoussé, Luc1 aChen, Yii-Der Ida1 aFerrucci, Luigi1 aFornage, Myriam1 aMozafarrian, Dariush1 aTsai, Michael, Y1 aSteffen, Lyn, M uhttps://chs-nhlbi.org/node/656703799nas a2200757 4500008004100000022001400041245019200055210006900247260001300316300001200329490000700341520158600348653002301934653002101957653004101978653001902019653000902038653002602047653002602073653002502099653002702124653001602151653002502167653001102192653001102203653000902214653001602223653003602239100002002275700002002295700002702315700001902342700001802361700001302379700002002392700002302412700001502435700001902450700002002469700002002489700002502509700002502534700001902559700002202578700002102600700001802621700002002639700001802659700002202677700002102699700002502720700002202745700001702767700002302784700002002807700002102827700001902848700001202867700001302879700001902892700002502911700002402936700002102960700002402981856003603005 2015 eng d a1613-413300aDietary fatty acids modulate associations between genetic variants and circulating fatty acids in plasma and erythrocyte membranes: Meta-analysis of nine studies in the CHARGE consortium.0 aDietary fatty acids modulate associations between genetic varian c2015 Jul a1373-830 v593 aSCOPE: Tissue concentrations of omega-3 fatty acids may reduce cardiovascular disease risk, and genetic variants are associated with circulating fatty acids concentrations. Whether dietary fatty acids interact with genetic variants to modify circulating omega-3 fatty acids is unclear. We evaluated interactions between genetic variants and fatty acid intakes for circulating alpha-linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid.
METHODS AND RESULTS: We conducted meta-analyses (N = 11 668) evaluating interactions between dietary fatty acids and genetic variants (rs174538 and rs174548 in FADS1 (fatty acid desaturase 1), rs7435 in AGPAT3 (1-acyl-sn-glycerol-3-phosphate), rs4985167 in PDXDC1 (pyridoxal-dependent decarboxylase domain-containing 1), rs780094 in GCKR (glucokinase regulatory protein), and rs3734398 in ELOVL2 (fatty acid elongase 2)). Stratification by measurement compartment (plasma versus erthyrocyte) revealed compartment-specific interactions between FADS1 rs174538 and rs174548 and dietary alpha-linolenic acid and linoleic acid for docosahexaenoic acid and docosapentaenoic acid.
CONCLUSION: Our findings reinforce earlier reports that genetically based differences in circulating fatty acids may be partially due to differences in the conversion of fatty acid precursors. Further, fatty acids measurement compartment may modify gene-diet relationships, and considering compartment may improve the detection of gene-fatty acids interactions for circulating fatty acid outcomes.
10aAcetyltransferases10aAcyltransferases10aAdaptor Proteins, Signal Transducing10aCarboxy-Lyases10aDiet10aDocosahexaenoic Acids10aEicosapentaenoic Acid10aErythrocyte Membrane10aFatty Acid Desaturases10aFatty Acids10aFatty Acids, Omega-310aFemale10aHumans10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide1 aSmith, Caren, E1 aFollis, Jack, L1 aNettleton, Jennifer, A1 aFoy, Millennia1 aH Y Wu, Jason1 aMa, Yiyi1 aTanaka, Toshiko1 aManichakul, Ani, W1 aWu, Hongyu1 aChu, Audrey, Y1 aSteffen, Lyn, M1 aFornage, Myriam1 aMozaffarian, Dariush1 aKabagambe, Edmond, K1 aFerruci, Luigi1 aChen, Yii-Der Ida1 aRich, Stephen, S1 aDjoussé, Luc1 aRidker, Paul, M1 aTang, Weihong1 aMcKnight, Barbara1 aTsai, Michael, Y1 aBandinelli, Stefania1 aRotter, Jerome, I1 aHu, Frank, B1 aChasman, Daniel, I1 aPsaty, Bruce, M1 aArnett, Donna, K1 aKing, Irena, B1 aSun, Qi1 aWang, Lu1 aLumley, Thomas1 aChiuve, Stephanie, E1 aSiscovick, David, S1 aOrdovas, Jose, M1 aLemaitre, Rozenn, N uhttps://chs-nhlbi.org/node/6687