Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci

Human Molecular Genetics, Feb 2015

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.

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Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci

Human Molecular Genetics Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci Meian He 0 4 Min Xu 0 1 3 Ben Zhang 0 Jun Liang 0 Peng Chen 0 Jong-Young Lee 0 Todd A. Johnson 0 Huaixing Li 0 Xiaobo Yang 0 Juncheng Dai 0 Liming Liang 0 3 Lixuan Gui 4 Qibin Qi 3 Jinyan Huang 3 Yanping Li 3 Linda S. Adair Tin Aung Qiuyin Cai Ching-Yu Cheng Myeong-Chan Cho Yoon Shin Cho Minjie Chu Bin Cui 1 Yu-Tang Gao Min Jin Go Dongfeng Gu Weiqiong Gu 1 Huan Guo 4 Yongchen Hao Jie Hong 1 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 4 JianJun Liu Jirong Longe Wei Lu Xiangfeng Lu Xiaoping Miao 4 Yukinori Okada Rick Twee-Hee Ong Gaokun Qiu 4 Mark Seielstad Xueling Sim Huaidong Song Fumihiko Takeuchi Toshihiro Tanaka Phil R. Taylor Laiyuan Wang Weiqing Wang 1 Yiqin Wang Chen Wu Ying Wu Yong-Bing Xiang Ken Yamamoto Handong Yang Ming Liao Mitsuhiro Yokota Terri Young Xiaomin Zhang 4 Norihiro Kato Qing K. Wang Wei Zheng Frank B. Hu 3 Dongxin Lin Hongbing Shen 2 Yik Ying Teo 2 Zengnan Mo 2 Tien Yin Wong 2 Xu Lin 2 Karen L. Mohlke 2 Guang Ning 1 2 Tatsuhiko Tsunoda 2 Bok-Ghee Han 2 Xiao-Ou Shu 2 E. Shyong Tai 2 Tangchun Wu 2 4 Lu Qi 2 3 0 Co-first authors 1 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 2 Co-last authors 3 Department of Nutrition, Harvard School of Public Health , Boston, MA 02115 , USA 4 MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology , Hubei, Wuhan 430030 , China - Diseases, Department of Endocrinology and Metabolism and 4State 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, 5Vanderbilt Epidemiology Center, Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA, 6Department of Endocrinology, The Central Hospital of Xuzhou, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu 221009, China, 7Saw Swee Hock School of Public Health, 8Department of Ophthalmology, 9Department of Paediatrics National University Health Systems, 10Department of Medicine, Yong Loo Lin School of Medicine, 11NUS Graduate School for Integrative Science and Engineering, 12Life Sciences Institute, 13Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore 119077, 14Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do 363-700, Republic of Korea, 15Laboratory for Medical Informatics, 16Laboratory for Genotyping Development, 17Laboratory for Statistical Analysis, 18Laboratory for Cardiovascular Diseases, RIKEN Center for Genomic Medicine, Yokohama 230-0045, Japan, 19Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, 20Institute of Urology and Nephrology, First Affiliated Hospital & Center for Genomic and Personalized Medicine, 21Medical Scientific Research Center and 22Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi 530021, China, 23Department of Epidemiology & Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China, 24Department of Nutrition and 25Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA, 26Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore 168751, 27Duke-National University of Singapore Graduate Medical School, Singapore, Singapore 169857, 28Department of Epidemiology, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China, 29State Key Laboratory of Cardiovascular Disease, Department of Evidence Based Medicine, Fuwai Hospital, National Center of Cardiovascular Diseases, 30State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China, 31Department of Ophthalmology, Erasmus Medical Center, Rotterdam 3015, The Netherlands, 32Memory Aging & Cognition Centre, National University Health System, Singapore, Singapore 119228, 33Department of Preventive Medicine, Seoul National University, College of Medicine, Seoul 110-799, Republic of Korea, 34Agency for Science, Technology and Research, Genome Institute of Singapore, Singapore, Singapore 138672, 35Office of Population Studies Foundation, University of San Carlos, Cebu City (...truncated)


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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. Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci, Human Molecular Genetics, 2015, pp. 1791-1800, 24/6, DOI: 10.1093/hmg/ddu583