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 Ichihara, Michiya 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
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. © The Author 2013. Published by Oxford University Press. All rights reserved.
Department of Genetics, University of North Carolina, Chapel Hill, NC, United States; Department of Nutrition, University of North Carolina, Chapel Hill, NC, United States; Saw Swee Hock School of Public Health, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore; Duke-NUS Graduate Medical School, National University of Singapore, Singapore; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academyof Sciences, Shanghai, China; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan; Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan; Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan Town, Miaoli, Taiwan; Institute of Statistics, National Chiao Tung University, Hsinchu, Taiwan; Institute for Health Promotion and Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, United States; USC-Office of Population Studies Foundation, University of San Carlos, Cebu City, Philippines; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan; Division of Endocrinology and Metabolism, Tri-ServiceGeneral Hospital, National Defense Medical Center, Taipei, Taiwan; Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; Graduate School of Regional Innovation Studies, Mie University, Tsu, Japan; Department of Geriatric Medicine, Ehime University Graduate School ofMedicine, Toon, Japan; Department ofCommunity Medicine, Ehime University Graduate School ofMedicine, Toon, Japan; Department of Molecular and Genetic Medicine, Ehime University Graduate School ofMedicine, Toon, Japan; Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan; Department of Anthropology, The Institute for Policy Research, Northwestern University, Evanston, IL, United States; Cells 2 Society: The Center for Social Disparities and Health, The Institute for Policy Research, Northwestern University, Evanston, IL, United States; Human Genetics, Genome Institute of Singapore, Singapore; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan; Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan; Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Division of Genome Analysis, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; Division of Neuroscience and Behavioral Disorders, Duke-National University of Singapore Graduate Medical School, Singapore; Department of Ophthalmology, Duke University Medical Center, Durham,NC, United States; Department of Internal Medicine, Korea University Ansan Hospital, Ansan, South Korea; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Genome Science, Aichi-Gakuin University School of Dentistry, Nagoya, Japan
