Tanika N. Kelly, Fumihiko Takeuchi, Yasuharu Tabara, Todd L. Edwards, Young Jin Kim, Peng Chen, Huaixing Li, Ying Wu, Chi-Fan Yang, Yonghong Zhang, Dongfeng Gu, Tomohiro Katsuya, Takayoshi Ohkubo, Yu-Tang Gao, Min Jin Go, Yik Ying Teo, Ling Lu, Nanette R. Lee, Li-Ching Chang, Hao Peng, Qi Zhao, Eitaro Nakashima, Yoshikuni Kita, Xiao-Ou Shu, Nam Hee Kim, E. Shyong Tai, Yiqin Wang, Linda S. Adair, Chien-Hsiun Chen, Shihiu Zhang, Changwei Li, Toru Nabika, Satoshi Umemura, Qiuyin Cai, Yoon Shin Cho, Tien Yin Wong, Jingwen Zhu, Jer-Yuarn Wu, Xin Gao, James E. Hixson, Hui Cai, Juyoung Lee, Ching-Yu Cheng, Dabeeru C. Rao, Yong-Bing Xiang, Myeong-Chan Cho, Bok-Ghee Han, Aili Wang, Fuu-Jen Tsai, Karen Mohlke, Xu Lin, Mohammad Kamran Ikram, Jong-Young Lee, Wei Zheng, Miki Tetsuro, Norihiro Kato, Jiang He
We conducted a genome-wide association study meta-analysis of mean arterial pressure and pulse pressure among 26 600 East Asian participants (stage 1) followed by replication study of up to 28 783 participants (stage 2). For novel loci, statistical significance was determined by a P<5.0×10 in joint analysis of stage 1 and stage 2 data. For loci reported by the previous mean arterial and pulse pressure genome-wide association study meta-analysis in Europeans, evidence of transethnic replication was determined by consistency in effect direction and a Bonferroni-corrected P<1.4×10. No novel loci were identified by the current study. Five independent mean arterial pressure variants demonstrated robust evidence for transethnic replication including rs17249754 at ATP2B1 (P=7.5×10), rs2681492 at ATP2B1 (P=3.4×10), rs11191593 at NT5C2 (1.1×10), rs3824755 at CYP17A1 (P=1.2×10), and rs13149993 at FGF5 (P=2.4×10). Two additional variants showed suggestive evidence of transethnic replication (consistency in effect direction and P<0.05), including rs319690 at MAP4 (P=0.014) and rs1173771 at NPR3 (P=0.018). For pulse pressure, robust evidence of replication was identified for 2 independent variants, including rs17249754 at ATP2B1 (P=1.2×10) and rs11191593 at NT5C2 (P=1.1×10), with suggestive evidence of replication among an additional 2 variants including rs3824755 at CYP17A1 (P=6.1×10) and rs2681492 at ATP2B1 (P=9.0×10). Replicated variants demonstrated consistency in effect sizes between East Asian and European samples, with effect size differences ranging from 0.03 to 0.24 mm Hg for mean arterial pressure and from 0.03 to 0.21 mm Hg for pulse pressure. In conclusion, we present the first evidence of transethnic replication of several mean arterial and pulse pressure loci in an East Asian population. © 2013 American Heart Association, Inc.
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, 1440 Canal St, United States; Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan; Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States; Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, South Korea; Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore; Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China; Department of Genetics, University of North Carolina, Chapel Hill, NC, United States; National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China; Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chinese National Center for Cardiovascular Disease Control and Research, Beijing, China; Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Japan; Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan; Department of Health Science, Shiga University of Medical Science, Shiga, Japan; Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan; Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore; NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, Singapore; Life Sciences Institute, National University of Singapore, Singapore, Singapore; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore; Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore; Office of Population Studies Foundation, University of San Carlos, Cebu City, Philippines, Philippines; Department of Diabetes and Endocrinology, Chubu Rosai Hospital, Nagoya, Japan; Division of Endocrinology and Diabetes, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Medicine, Yong Loo Lin School of Medicine and National University of Singapore, National University Health System, Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore, Singapore; Department of Nutrition, University of North Carolina, Chapel Hill, United States; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan; Department of Medical Science and Cardiorenal Medicine, Yokohama City University School of Medicine, Yokohama, Japan; Department of Biomedical Science, Hallym University, Gwangwon-do, South Korea; Department of Ophthalmology, National University of Singapore and National University Health System, Singapore, Singapore; Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore; Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, OH, United States; Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore, Singapore; Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States; National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, South Korea; Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan; Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, Japan; Department of Medicine, Tulane University School of Medicine, New Orleans, LA, United States
