Meian He, Min Xu, Ben Zhang, Jun Liang, Peng Chen, Jong-Young Lee, Todd A. Johnson, Huaixing Li, Xiaobo Yang, Juncheng Dai, Liming Liang, Lixuan Gui, Qibin Qi, Jinyan Huang, Yanping Li, Linda S. Adair, Tin Aung, Qiuyin Cai, Ching-Yu Cheng, Myeong-Chan Cho, Yoon Shin Cho, Minjie Chu, Bin Cui, Yu-Tang Gao, Min Jin Go, Dongfeng Gu, Weiqiong Gu, Huan Guo, Yongchen Hao, Jie Hong, Zhibin Hu, Yanling Hu, Jianfeng Huang, Joo-Yeon Hwang, Mohammad Kamran Ikram, Guangfu Jin, Dae-Hee Kang, Chiea Chuen Khor, Bong-Jo Kim, Hung Tae Kim, Michiaki Kubo, Jeannette Lee, Juyoung Lee, Nanette R. Lee, Ruoying Li, Jun Li, JianJun Liu, Jirong Longe, Wei Lu, Xiangfeng Lu, Xiaoping Miao, Yukinori Okada, Rick Twee-Hee Ong, Gaokun Qiu, Mark Seielstad, Xueling Sim, Huaidong Song, Fumihiko Takeuchi, Toshihiro Tanaka, Phil R. Taylor, Laiyuan Wang, Weiqing Wang, Yiqin Wang, Chen Wu, Ying Wu, Yong-Bing Xiang, Ken Yamamoto, Handong Yang, Ming Liao, Mitsuhiro Yokota, Terri Young, Xiaomin Zhang, Norihiro Kato, Qing K. Wang, Wei Zheng, Frank B. Hu, Dongxin Lin, Hongbing Shen, Yik Ying Teo, Zengnan Mo, Tien Yin Wong, Xu Lin, Karen L. Mohlke, Guang Ning, Tatsuhiko Tsunoda, Bok-Ghee Han, Xiao-Ou Shu, E. Shyong Tai, Tangchun Wu, Lu Qi
Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity. Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci. A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns. We carried out a GWA meta-analysis in 93 926 individuals from East Asia. We identified 98 loci, including 17 novel and 81 previously reported loci, associated with height at P < 5 × 10-8, together explaining 8.89% of phenotypic variance. Among the newly identified variants, 10 are commonly distributed (minor allele frequency, MAF > 5%) in Europeans, with comparable frequencies with in Asians, and 7 single-nucleotide polymorphisms are with low frequency (MAF < 5%) in Europeans. In addition, our data suggest that novel biological pathway such as the protein tyrosine phosphatase family is involved in regulation of height. The findings from this study considerably expand our knowledge of the genetic architecture of human height in Asians. © The Author 2014. Published by Oxford University Press. All rights reserved.
MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, 430030, China; Department of Nutrition, Harvard School of Public Health, Boston, 02115, MA, United States; Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai, 200025, China; State Key Laboratory of Medical Genomics, Molecular Medical Center, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Vanderbilt Epidemiology Center, Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, 37232, TN, United States; Department of Endocrinology, The Central Hospital of Xuzhou, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu, 221009, China; Saw Swee Hock School of Public Health, National University of Singapore, Singapore, 119077, Singapore; Department of Ophthalmology, National University of Singapore, Singapore, 119077, Singapore; Department of Paediatrics National University Health Systems, National University of Singapore, Singapore, 119077, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119077, Singapore; NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, 119077, Singapore; Life Sciences Institute, National University of Singapore, Singapore, 119077, Singapore; Department of Statistics and Applied Probability, National University of Singapore, Singapore, 119077, Singapore; Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, 363-700, South Korea; Laboratory for Medical Informatics, RIKEN Center for Genomic Medicine, Yokohama, 230-0045, Japan; Laboratory for Genotyping Development, RIKEN Center for Genomic Medicine, Yokohama, 230-0045, Japan; Laboratory for Statistical Analysis, RIKEN Center for Genomic Medicine, Yokohama, 230-0045, Japan; Laboratory for Cardiovascular Diseases, RIKEN Center for Genomic Medicine, Yokohama, 230-0045, Japan; Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China; Institute of Urology and Nephrology, First Affiliated Hospital, Center for Genomic and Personalized Medicine, Nanning, Guangxi, 530021, China; Medical Scientific Research Center, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China; Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China; Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 210029, China; Department of Nutrition, University of North Carolina, Chapel Hill, 27599, NC, United States; Department of Genetics, University of North Carolina, Chapel Hill, 27599, NC, United States; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, 168751, Singapore; Duke-National University, Singapore Graduate Medical School, Singapore, 169857, Singapore; Department of Epidemiology, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; State Key Laboratory of Cardiovascular Disease, Department of Evidence Based Medicine, Fuwai Hospital, National Center of Cardiovascular Diseases, Beijing, 100730, China; State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, 3015, Netherlands; Memory Aging and Cognition Centre, National University Health System, Singapore, 119228, Singapore; Department of Preventive Medicine, Seoul National University, College of Medicine, Seoul, 110-799, South Korea; Agency for Science, Technology and Research, Genome Institute of Singapore, Singapore, 138672, Singapore; Office of Population Studies Foundation, University of San Carlos, Cebu City, 6000, Philippines; Shanghai Municipal Center for Disease Control and Prevention, 1380 Zhong Shan Road (W), Shanghai, 200336, China; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109-2029, MI, United States; Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan; Division of Cancer Epidemiology and Genetics, Genetic Epidemiology Branch, National Cancer Institute, Bethesda, 20892, MD, United States; Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan; Department of Cardiology, Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei, 442008, China; Department of Genome Science, Aichi-Gakuin University, School of Dentistry, Nagoya, 464-8650, Japan; Duke Eye Center, Duke University Medical Center, Durham, 27710, NC, United States; Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China
