A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2

• Published in: Human molecular genetics 2014-02, Vol.23 (4), p.1108-1119
• Main Authors: Wu, Ying, Gao, He, Li, Huaixing, Tabara, Yasuharu, Nakatochi, Masahiro, Chiu, Yen-Feng, Park, Eun Jung, Wen, Wanqing, Adair, Linda S, Borja, Judith B, Cai, Qiuyin, Chang, Yi-Cheng, Chen, Peng, Croteau-Chonka, Damien C, Fogarty, Marie P, Gan, Wei, He, Chih-Tsueng, Hsiung, Chao A, Hwu, Chii-Min, Ichihara, Sahoko, Igase, Michiya, Jo, Jaeseong, Kato, Norihiro, Kawamoto, Ryuichi, Kuzawa, Christophor W, Lee, Jeannette J M, Liu, Jianjun, Lu, Ling, McDade, Thomas W, Osawa, Haruhiko, Sheu, Wayne H-H, Teo, Yvonne, Vadlamudi, Swarooparani, Van Dam, Rob M, Wang, Yiqin, Xiang, Yong-Bing, Yamamoto, Ken, Ye, Xingwang, Young, Terri L, Zheng, Wei, Zhu, Jingwen, Shu, Xiao-Ou, Shin, Chol, Jee, Sun Ha, Chuang, Lee-Ming, Miki, Tetsuro, Yokota, Mitsuhiro, Lin, Xu, Mohlke, Karen L, Tai, E Shyong
• Format: Article
• Language: English
• Subjects: Adiponectin - blood; Asian Continental Ancestry Group; Association Studies; Cardiovascular Diseases - blood; Cardiovascular Diseases - genetics; Cohort Studies; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Membrane Proteins - genetics; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins - genetics; Receptor, Fibroblast Growth Factor, Type 2 - genetics
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddt488

Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associated loci, particularly those of importance in East Asians, we conducted a meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two stages of replications in 4298 and 5954 additional individuals. We identified a novel adiponectin-associated locus on chromosome 10 near WDR11-FGFR2 (P = 3.0 × 10(-14)) and provided suggestive evidence for a locus on chromosome 12 near OR8S1-LALBA (P = 1.2 × 10(-7)). Of the adiponectin-associated loci previously described, we confirmed the association at CDH13 (P = 6.8 × 10(-165)), ADIPOQ (P = 1.8 × 10(-22)), PEPD (P = 3.6 × 10(-12)), CMIP (P = 2.1 × 10(-10)), ZNF664 (P = 2.3 × 10(-7)) and GPR109A (P = 7.4 × 10(-6)). Conditional analysis at ADIPOQ revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (Pinitial = 0.020; Pconditional = 7.0 × 10(-7)). We further confirmed the independence of two pairs of closely located loci (