Fumihiko Takeuchi, Masato Akiyama, Nana Matoba, Tomohiro Katsuya, Masahiro Nakatochi, Yasuharu Tabara, Akira Narita, Woei-Yuh Saw, Sanghoon Moon, Cassandra N. Spracklen, Jin-Fang Chai, Young-Jin Kim, Liang Zhang, Chaolong Wang, Huaixing Li, Honglan Li, Jer-Yuarn Wu, Rajkumar Dorajoo, Jovia L. Nierenberg, Ya Xing Wang, Jing He, Derrick A. Bennett, Atsushi Takahashi, Yukihide Momozawa, Makoto Hirata, Koichi Matsuda, Hiromi Rakugi, Eitaro Nakashima, Masato Isono, Matsuyuki Shirota, Atsushi Hozawa, Sahoko Ichihara, Tatsuaki Matsubara, Ken Yamamoto, Katsuhiko Kohara, Michiya Igase, Sohee Han, Penny Gordon-Larsen, Wei Huang, Nanette R. Lee, Linda S. Adair, Mi Yeong Hwang, Juyoung Lee, Miao Li Chee, Charumathi Sabanayagam, Wanting Zhao, Jianjun Liu, Dermot F. Reilly, Liang Sun, Shaofeng Huo, Todd L. Edwards, Jirong Long, Li-Ching Chang, Chien-Hsiun Chen, Jian-Min Yuan, Woon-Puay Koh, Yechiel Friedlander, Tanika N. Kelly, Wen Bin Wei, Liang Xu, Hui Cai, Yong-Bing Xiang, Kuang Lin, Robert Clarke, Robin G. Walters, Iona Y. Millwood, Liming Li, John C. Chambers, Jaspal S. Kooner, Paul Elliott, Pim van der Harst, Marie Loh, Niek Verweij, Weihua Zhang, Benjamin Lehne, Irene Mateo Leach, Alexander Drong, James Abbott, Sian-Tsung Tan, William R. Scott, Gianluca Campanella, Marc Chadeau-Hyam, Uzma Afzal, Tõnu Esko, Sarah E. Harris, Jaana Hartiala, Marcus E. Kleber, Richa Saxena, Alexandre F. R. Stewart, Tarunveer S. Ahluwalia, Imke Aits, Alexessander Da Silva Couto Alves, Shikta Das, Jemma C. Hopewell, Robert W. Koivula, Leo-Pekka Lyytikäinen, Iris Postmus, Olli T. Raitakari, Robert A. Scott, Rossella Sorice, Vinicius Tragante, Michela Traglia, Jon White, Inês Barroso, Andrew Bjonnes, Rory Collins, Gail Davies, Graciela Delgado, Pieter A. Doevendans, Lude Franke, Ron T. Gansevoort, Tanja B. Grammer, Niels Grarup, Jagvir Grewal, Anna-Liisa Hartikainen, Stanley L. Hazen, Chris Hsu, Lise L. N. Husemoen, Johanne M. Justesen, Meena Kumari, Wolfgang Lieb, David C. M. Liewald, Evelin Mihailov, Lili Milani, Rebecca Mills, Nina Mononen, Kjell Nikus, Teresa Nutile, Sarah Parish, Olov Rolandsson, Daniela Ruggiero, Cinzia F. Sala, Harold Snieder, Thomas H. W. Spasø, Wilko Spiering, John M. Starr, David J. Stott, Daniel O. Stram, Silke Szymczak, W. H. Wilson Tang, Stella Trompet, Väinö Turjanmaa, Marja Vaarasmaki, Wiek H. van Gilst, Dirk J. van Veldhuisen, Jorma S. Viikari, Folkert W. Asselbergs, Marina Ciullo, Andre Franke, Paul W. Franks, Steve Franks, Myron D. Gross, Torben Hansen, Marjo-Riitta Jarvelin, Torben Jørgensen, Wouter J. Jukema, Mika Kähönen, Mika Kivimaki, Terho Lehtimäki, Allan Linneberg, Oluf Pedersen, Nilesh J. Samani, Daniela Toniolo, Hooman Allayee, Ian J. Deary, Winfried März, Andres Metspalu, Cisca Wijmenga, Bruce H. W. Wolffenbuttel, Paolo Vineis, Soterios A. Kyrtopoulos, Jos C. S. Kleinjans, Mark I. McCarthy, James Scott, Zhengming Chen, Makoto Sasaki, Xiao-Ou Shu, Jost B. Jonas, Jiang He, Chew-Kiat Heng, Yuan-Tsong Chen, Wei Zheng, Xu Lin, Yik-Ying Teo, E-Shyong Tai, Ching-Yu Cheng, Tien Yin Wong, Xueling Sim, Karen L. Mohlke, Masayuki Yamamoto, Bong-Jo Kim, Tetsuro Miki, Toru Nabika, Mitsuhiro Yokota, Yoichiro Kamatani, Michiaki Kubo, Norihiro Kato
Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP. © 2018, The Author(s).
Medical Genomics Center, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan; Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan; Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan; Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan; Data Coordinating Center, Department of Advanced Medicine, Nagoya University Hospital, Nagoya, 466-8560, Japan; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, 980-8573, Japan; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, 117549, Singapore; Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore; Division of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, 363-951, South Korea; Department of Genetics, University of North Carolina, Chapel Hill, NC 27514, United States; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, 168751, Singapore; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, 138672, Singapore; Duke-NUS Medical School, Singapore, 169857, Singapore; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; CAS Key Laboratory of Nutrition, Metabolism and Food safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China; State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China; Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan; School of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, United States; Beijing Institute of Ophthalmology, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China; Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN 37203-1738, United States; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, United Kingdom; Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Osaka, 565-0873, Japan; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan; Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan; Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, 277-8561, Japan; Division of Endocrinology and Diabetes, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan; Department of Diabetes and Endocrinology, Chubu Rosai Hospital, Nagoya, 455-8530, Japan; Department of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke, 329-0498, Japan; Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, 470-0195, Japan; Department of Medical Biochemistry, Kurume University School of Medicine, Kurume, 830-0011, Japan; Faculty of Collaborative Regional Innovation, Ehime University, Matsuyama, 790-8577, Ehime, Japan; Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, 791-0295, Ehime, Japan; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; 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Division of Cancer Control and Population Sciences, UPMC Hillman Cancer, University of Pittsburgh, Pittsburgh, PA 15232, United States; Health Services and Systems Research, Duke-NUS Medical School, Singapore, 169857, Singapore; Unit of Epidemiology, Hebrew University-Hadassah Braun School of Public Health, Jerusalem, P.O. 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Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, OX3 7LE, United Kingdom
