Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations

作者：Yao Hu, Toshiko Tanaka, Jingwen Zhu, Weihua Guan, Jason Wu, Bruce M. Psaty, Barbara McKnight, Irena B. King, Qi Sun, Melissa A. Richard, Ani Manichaikul, Alexis C. Wood, Edmond K. Kabagambe, Paul N. Hopkins, José M. Ordovás, Luigi Ferrucci, Stefania Bandinelli, Donna K. Arnett, Yii-Der I. Chen, Shuang Liang, David S. Siscovick, Michael Y. Tsai, Stephen S. Rich, Myriam Fornage, Frank B. Hu, Eric B. Rimm, Majken K. Jensen, Rozenn N. Lemaître, Dariush Mozaffarian, Lyn M. Steffen, Andrew P. Morris, Huaixing Li, Lin Xu · 发表于：Journal of Lipid Research · 年份：2017 · DOI：10.1194/jlr.p071860 · 被引用次数：25 · 研究领域：Genetic Associations and Epidemiology、Lipid metabolism and biosynthesis、Cancer-related molecular mechanisms research

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 i...