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oai:repisalud.isciii.es:20.500.12105/51202024-09-27T08:00:36Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Hu, Yao author Tanaka, Toshiko author Zhu, Jingwen author Guan, Weihua author Wu, Jason H. Y. author Psaty, Bruce M. author McKnight, Barbara author King, Irena B. author Sun, Qi author Richard, Melissa author Manichaikul, Ani author Frazier-Wood, Alexis C. author Kabagambe, Edmond K. author Hopkins, Paul N. author Ordovas, Jose M author Ferrucci, Luigi author Bandinelli, Stefania author Arnett, Donna K author Chen, Yii-Der I. author Liang, Shuang author Siscovick, David S. author Tsai, Michael Y. author Rich, Stephen S. author Fornage, Myriam author Hu, Frank author Rimm, Eric B. author Jensen, Majken K. author Lemaitre, Rozenn N author Mozaffarian, Dariush author Steffen, Lyn M. author Morris, Andrew P. author Li, Huaixing author Lin, Xu author 2017 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 [log(10)(Bayes factor). >= 8.07] and for gondoic acid at FADS1/2 and GCKR [log(10)(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.(jl) Our findings provide novel insight into the genetic basis relevant to MUFA metabolism and biology. J Lipid Res. 2017; 58(5):974-981 10.1194/jlr.P071860 1539-7262 0022-2275 Journal of Lipid Research 28298293 http://hdl.handle.net/20.500.12105/5120 Genetics Fatty acid/desaturases Fatty acid/metabolism Fatty acid/biosynthesis Monounsaturated fatty acid GENOME-WIDE ASSOCIATION MONOUNSATURATED FATTY-ACIDS NOVO LIPOGENESIS PATHWAY CORONARY-HEART-DISEASE C-REACTIVE PROTEIN METABOLIC SYNDROME OLDER CHINESE PALMITOLEIC ACID ADIPOSE-TISSUE RISK Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations