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

Ying Wu, He Gao, Huaixing Li, Yasuharu Tabara, Masahiro Nakatochi, Yen Feng Chiu, Eun Jung Park, Wanqing Wen, Linda S. Adair, Judith B. Borja, Qiuyin Cai, Yi Cheng Chang, Peng Chen, Damien C. Croteau-Chonka, Marie P. Fogarty, Wei Gan, Chih Tsueng He, Chao A. Hsiung, Chii Min Hwu, Sahoko IchiharaMichiya Igase, Jaeseong Jo, Norihiro Kato, Ryuichi Kawamoto, Christophor W. Kuzawa, Jeannette J.M. Lee, Jianjun Liu, Ling Lu, Thomas W. Mcdade, Haruhiko Osawa, Wayne H.H. Sheu, Yvonne Teo, Swarooparani Vadlamudi, Rob M. Van Dam, Yiqin Wang, Yong Bing Xiang, Ken Yamamoto, Xingwang Ye, Terri L. Young, Wei Zheng, Jingwen Zhu, Xiao Ou Shu, Chol Shin, Sun Ha Jee, Lee Ming Chuang, Tetsuro Miki, Mitsuhiro Yokota, Xu Lin, Karen L. Mohlke, E. Shyong Tai

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Abstract

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 adiponectinassociated 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 (<2 Mb) on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664. In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of association with triglycerides (P = 3.3 × 10-4), high density lipoprotein cholesterol (HDL-C, P = 4.9 × 10-4) and body mass index (BMI)-adjusted waist-hip ratio (P = 9.8 × 10-3). These findings improve our knowledge of the genetic basis of adiponectin variation, demonstrate the shared allelic architecture for adiponectin with lipids and central obesity and motivate further studies of underlying mechanisms.

Original languageEnglish
Article numberddt488
Pages (from-to)1108-1119
Number of pages12
JournalHuman Molecular Genetics
Volume23
Issue number4
DOIs
Publication statusPublished - 2014 Feb

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Wu, Y., Gao, H., Li, H., Tabara, Y., Nakatochi, M., Chiu, Y. F., Park, E. J., Wen, W., Adair, L. S., Borja, J. B., Cai, Q., Chang, Y. C., Chen, P., Croteau-Chonka, D. C., Fogarty, M. P., Gan, W., He, C. T., Hsiung, C. A., Hwu, C. M., ... Tai, E. S. (2014). A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2. Human Molecular Genetics, 23(4), 1108-1119. [ddt488]. https://doi.org/10.1093/hmg/ddt488