Xiangfeng Lu, Gina M. Peloso, Dajiang J. Liu, Ying Wu, He Zhang, Wei Zhou, Jun Li, Clara Sze-Man Tang, Rajkumar Dorajoo, Huaixing Li, Jirong Long, Xiuqing Guo, Ming Xu, Cassandra N. Spracklen, Yang Chen, Xuezhen Liu, Yan Zhang, Chiea Chuen Khor, Jianjun Liu, Liang Sun, Laiyuan Wang, Yu-Tang Gao, Yao Hu, Kuai Yu, Yiqin Wang, Chloe Yu Yan Cheung, Feijie Wang, Jianfeng Huang, Qiao Fan, Qiuyin Cai, Shufeng Chen, Jinxiu Shi, Xueli Yang, Wanting Zhao, Wayne H-H Sheu, Stacey Shawn Cherny, Meian He, Alan B. Feranil, Linda S. Adair, Penny Gordon-Larsen, Shufa Du, Rohit Varma, Yii-Der Ida Chen, Xiao-Ou Shu, Karen Siu Ling Lam, Tien Yin Wong, Santhi K. Ganesh, Zengnan Mo, Kristian Hveem, Lars G. Fritsche, Jonas Bille Nielsen, Hung-Fat Tse, Yong Huo, Ching-Yu Cheng, Y Eugene Chen, Wei Zheng, E Shyong Tai, Wei Gao, Xu Lin, Wei Huang, Goncalo Abecasis, Sekar Kathiresan, Karen L Mohlke, Tangchun Wu, Pak Chung Sham, Dongfeng Gu, Cristen J. Willer
Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci. © 2017 Nature America, Inc.
Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States; Department of Human Genetics, University of Michigan, Ann Arbor, MI, United States; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, United States; Department of Biostatistics, Boston University, School of Public Health, Boston, MA, United States; Department of Public Health Sciences, Institute of Personalized Medicine, Penn State University, University Park, PA, United States; Department of Genetics, University of North Carolina, Chapel Hill, NC, United States; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United States; MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Department of Surgery, Li KaShing Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore; Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, United States; Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Los Angeles, CA, United States; Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China; Center for Genomic and Personalized Medicine, Medical Scientific Research Center, Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Department of Cardiology, Peking University First Hospital, Beijing, China; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Department of Medicine, University of Hong Kong, Hong Kong, Hong Kong; Community Health Center, 3rd Affiliated Hospital of Shenzhen University, Shenzhen, China; Duke-National University of Singapore, Graduate Medical School, Singapore, Singapore; Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China; Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Psychiatry, University of Hong Kong, Hong Kong, Hong Kong; Centre for Genomic Sciences, Li KaShing Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong; State Key Laboratory of Brain and Cognitive Sciences, University of Hong Kong, Hong Kong, Hong Kong; USC-Office of Population Studies Foundation, University of San Carlos, Cebu City, Philippines; Department of Anthropology, Department of Sociology and History, University of San Carlos, Cebu City, Philippines; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States; Carolina Population Center, University of North Carolina, Chapel Hill, NC, United States; USC Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States; Research Centre of Heart Brai, Hormone and Healthy Aging, Li KaShing Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong; State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, Hong Kong; Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore; Department of Ophthalmology, National University of Singapore, Singapore, Singapore; HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway; Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway; Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, United States; Hong Kong-Guangdong Joint Laboratory On Stem Cell and Regenerative Medicine, University of Hong Kong, Hong Kong, Hong Kong; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States
