02956nas a2200505   4500000000100000008004100001100001700042700001100059700001900070700001600089700001600105700001600121700002100137700001500158700001100173700002000184700002000204700002400224700002100248700001700269700001700286700001900303700002400322700001700346700001700363700001700380700002000397700001700417700001700434700001900451700001300470700001400483700001800497700002000515700002400535700001600559700001800575700001600593700001100609245013300620300001200753490000700765520166400772022001402436       2017                            d1 aH Y Wu Jason1 aHu Yao1 aTanaka Toshiko1 aZhu Jingwen1 aGuan Weihua1 aPsaty Bruce1 aMcKnight Barbara1 aKing Irena1 aSun Qi1 aRichard Melissa1 aManichaikul Ani1 aFrazier-Wood Alexis1 aKabagambe Edmond1 aHopkins Paul1 aOrdovas Jose1 aFerrucci Luigi1 aBandinelli Stefania1 aArnett Donna1 aChen Yii-Der1 aLiang Shuang1 aSiscovick David1 aTsai Michael1 aRich Stephen1 aFornage Myriam1 aHu Frank1 aRimm Eric1 aJensen Majken1 aLemaitre Rozenn1 aMozaffarian Dariush1 aSteffen Lyn1 aMorris Andrew1 aLi Huaixing1 aLin Xu00aDiscovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations.  a974-9810 v583 a<p>
MUFAs are unsaturated FAs with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels are associated with cardiometabolic disorders, including CVD, T2D, and metabolic syndrome (MS). Previous genome-wide association studies (GWASs) have identified seven loci for plasma and erythrocyte palmitoleic and oleic acid levels in populations of European origin. To identify additional MUFA-associated loci and the potential functional variant at each locus, we performed ethnic-specific GWAS meta-analyses and trans-ethnic meta-analyses in more than 15,000 participants of Chinese and European ancestry. We identified novel genome-wide significant associations for vaccenic acid at FADS1/2 and PKD2L1 [log10(Bayes factor) ≥ 8.07] and for gondoic acid at FADS1/2 and GCKR [log10(Bayes factor) ≥ 6.22], and also observed improved fine-mapping resolutions at FADS1/2 and GCKR loci. The greatest improvement was observed at GCKR, where the number of variants in the 99% credible set was reduced from 16 (covering 94.8 kb) to 5 (covering 19.6 kb, including a missense variant rs1260326) after trans-ethnic meta-analysis. We also confirmed the previously reported associations of PKD2L1, FADS1/2, GCKR, and HIF1AN with palmitoleic acid and of FADS1/2 and LPCAT3 with oleic acid in the Chinese-specific GWAS and the trans-ethnic meta-analyses. Pathway-based analyses suggested that the identified loci were in unsaturated FA metabolism and signaling pathways. Our findings provide novel insight into the genetic basis relevant to MUFA metabolism and biology.
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  a1539-7262