Cassandra N. Spracklen, Peng Chen, Young Jin Kim, Xu Wang, Hui Cai, Shengxu Li, Jirong Long, Ying Wu, Ya Xing Wang, Fumihiko Takeuchi, Jer-Yuarn Wu, Keum-Ji Jung, Cheng Hu, Koichi Akiyama, Yonghong Zhang, Sanghoon Moon, Todd A. Johnson, Huaixing Li, Rajkumar Dorajoo, Meian He, Maren E. Cannon, Tamara S. Roman, Elias Salfati, Keng-Hung Lin, Xiuqing Guo, Wayne H.H. Sheu, Devin Absher, Linda S. Adair, Themistocles L. Assimes, Tin Aung, Qiuyin Cai, Li-Ching Chang, Chien-Hsiun Chen, Li-Hsin Chien, Lee-Ming Chuang, Shu-Chun Chuang, Shufa Du, Qiao Fan, Cathy S.J. Fann, Alan B. Feranil, Yechiel Friedlander, Penny Gordon-Larsen, Dongfeng Gu, Lixuan Gui, Zhirong Guo, Chew-Kiat Heng, James Hixson, Xuhong Hou, Chao Agnes Hsiung, Yao Hu, Mi Yeong Hwang, Chii-Min Hwu, Masato Isono, Jyh-Ming Jimmy Juang, Chiea-Chuen Khor, Yun Kyoung Kim, Woon-Puay Koh, Michiaki Kubo, I-Te Lee, Sun-Ju Lee, Wen-Jane Lee, Kae-Woei Liang, Blanche Lim, Sing-Hui Lim, Jianjun Liu, Toru Nabika, Wen-Harn Pan, Hao Peng, Thomas Quertermous, Charumathi Sabanayagam, Kevin Sandow, Jinxiu Shi, Liang Sun, Pok Chien Tan, Shu-Pei Tan, Kent D. Taylor, Yik-Ying Teo, Sue-Anne Toh, Tatsuhiko Tsunoda, Rob M. van Dam, Aili Wang, Feijie Wang, Jie Wang, Wen Bin Wei, Yong-Bing Xiang, Jie Yao, Jian-Min Yuan, Rong Zhang, Wanting Zhao, Yii-Der Ida Chen, Stephen S. Rich, Jerome I. Rotter, Tzung-Dau Wang, Tangchun Wu, Xu Lin, Bok-Ghee Han, Toshihiro Tanaka, Yoon Shin Cho, Tomohiro Katsuya, Weiping Jia, Sun-Ha Jee, Yuan-Tsong Chen, Norihiro Kato, Jost B. Jonas, Ching-Yu Cheng, Xiao-Ou Shu, Jiang He, Wei Zheng, Tien-Yin Wong, Wei Huang, Bong-Jo Kim, E-Shyong Tai, Karen L. Mohlke, Xueling Sim
Large-scale meta-analyses of genome-wide association studies (GWAS) have identified>175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS metaanalyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P<5×10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P=7.4×10-10), NCOA2 (P=1.6×10-8), and NID2-PTGDR (P=4.2×10-8), and one novel locus associated with TG near WDR11-FGFR2 (P=2.7×10-10). Conditional analyses identified a second signal near CD163-APOBEC1.We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor>6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P<1×10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets. © The Author 2017. Published by Oxford University Press. All rights reserved.
Department of Genetics, University of North Carolina, Chapel Hill, NC, United States; Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore; Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China; Division of Structural and Functional Genomics, Center for Genome Science, Korean National Institute of Health, Osong, Chungchungbuk-do, South Korea; Life Sciences Institute, National University of Singapore, Singapore; Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States; Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China; National Center for Global Health and Medicine, Tokyo, Japan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan; Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea; Shanghai Diabetes Institute, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China; Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China; Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore; Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College Huazhong University of Science and Technology, Wuhan, Hubei, China; Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States; Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Pediatrics, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, United States; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan; Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan; HudsonAlpha Institute for Biotechnology, Huntsville, AL, United States; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Duke-NUS Medical School Singapore, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan; Institute of Preventive Medicine, School of Public Health, National Taiwan University, Taipei, Taiwan; Carolina Population Center, University of North Carolina, Chapel Hill, NC, United States; USC-Office of Population Studies Foundation, Inc, University of San Carlos, Cebu City, Philippines; Department of Anthropology, Sociology and History, University of San Carlos, Cebu City, Philippines; Unit of Epidemiology, Hebrew University-Hadassah Braun School of Public Health, Jerusalem, Israel; Department of Epidemiology and Population Genetics, Fuwai Hospital, Beijing, China; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore; Human Genetics Center, University of Texas School of Public Health, Houston, TX, United States; Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Biochemistry, National University of Singapore, Singapore; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Social Work, Tunghai University, Taichung, Taiwan; Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medicine, China Medical University, Taichung, Taiwan; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan; Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute, Shanghai, China; NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore; Department of Statistics and Applied Probability, National University of Singapore, Singapore; Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan; Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Capital Medical University, Beijing, China; Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States; Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, PA, United States; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, United States; Center for Genome Science, Korean National Institute of Health, Osong, Chungchungbuk-do, South Korea; Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Department of Biomedical Science, Hallym University, Chuncheon, South Korea; Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Japan; Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Mannheim, Germany
