Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians

Changwei Li; Yun Kyoung Kim; Rajkumar Dorajoo; Huaixing Li; I-Te Lee; Ching-Yu Cheng; Meian He; Wayne H-H Sheu; Xiuqing Guo; Santhi K Ganesh; Jiang He; Juyoung Lee; Jianjun Liu; Yao Hu; Dabeeru C Rao; Fuu-Jen Tsai; Jia Yu Koh; Hua Hu; Kae-Woei Liang; Walter Palmas; James E Hixson; Sohee Han; Yik-Ying Teo; Yiqin Wang; Jing Chen; Chieh Hsiang Lu; Yingfeng Zheng; Lixuan Gui; Wen-Jane Lee; Jie Yao; Dongfeng Gu; Bok-Ghee Han; Xueling Sim; Liang Sun; Jinying Zhao; Chien-Hsiun Chen; Neelam Kumari; Yunfeng He; Kent D Taylor; Leslie J Raffel; Sanghoon Moon; Jerome I Rotter; Yii-der Ida Chen; Tangchun Wu; Tien Yin Wong; Jer-Yuarn Wu; Xu Lin; E-Shyong Tai; Bong-Jo Kim; Tanika N Kelly

doi:10.1161/CIRCGENETICS.116.001527

Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians

Circ Cardiovasc Genet. 2017 Apr;10(2):e001527. doi: 10.1161/CIRCGENETICS.116.001527.

Authors

Changwei Li¹, Yun Kyoung Kim¹, Rajkumar Dorajoo¹, Huaixing Li¹, I-Te Lee¹, Ching-Yu Cheng¹, Meian He¹, Wayne H-H Sheu¹, Xiuqing Guo¹, Santhi K Ganesh¹, Jiang He¹, Juyoung Lee¹, Jianjun Liu¹, Yao Hu¹, Dabeeru C Rao¹, Fuu-Jen Tsai¹, Jia Yu Koh¹, Hua Hu¹, Kae-Woei Liang¹, Walter Palmas¹, James E Hixson¹, Sohee Han¹, Yik-Ying Teo¹, Yiqin Wang¹, Jing Chen¹, Chieh Hsiang Lu¹, Yingfeng Zheng¹, Lixuan Gui¹, Wen-Jane Lee¹, Jie Yao¹, Dongfeng Gu¹, Bok-Ghee Han¹, Xueling Sim¹, Liang Sun¹, Jinying Zhao¹, Chien-Hsiun Chen¹, Neelam Kumari¹, Yunfeng He¹, Kent D Taylor¹, Leslie J Raffel¹, Sanghoon Moon¹, Jerome I Rotter¹, Yii-der Ida Chen¹, Tangchun Wu¹, Tien Yin Wong¹, Jer-Yuarn Wu¹, Xu Lin¹, E-Shyong Tai¹, Bong-Jo Kim¹, Tanika N Kelly²

Affiliations

¹ From the Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (C.L., J.H., J.Z., T.N.K.); Center for Genome Science, Korea National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Korea (Y.K.K., J.L., S.H., B.-G.H., S.M., B.-J.K.); Genome Institute of Singapore, Agency for Science, Technology and Research (R.D., J.L., Y.-Y.T.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences (H.L., Y.H., Y.W., L.S., X.L.); National Yang-Ming University Hospital, Taipei, Taiwan (I-T.L.); National Yang-Ming University Hospital, Taipei, Taiwan; Singapore Eye Research Institute, Singapore National Eye Center (Y.C., Y.K., Y.Z., N.K., T.Y.W.); Duke-NUS Graduate Medical School, National University of Singapore, (Y.C., N.K., T.Y.W., E-S.T.); Department of Ophthalmology (Y.C., T.Y.W.), Department of Statistics and Applied Probability (Y.-Y.T.), Life Sciences Institute (Y.-Y.T.), NUS Graduate School for Integrative Science and Engineering (Y.-Y.T.), Department of Medicine, National University Health System, Singapore (E-S.T.); MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (M.H., H.H., L.G., Y.H., T.W.); Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taipei, Taiwan (I-T.L., W.H-h.S); School of Medicine, National Yang-Ming University, Taipei, Taiwan (W.H-h.S., K.-W.L.); Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, CA (X.G., J.Y., K.D.T., J.I.R., Y.-d.I.C.); Division of Cardiovascular Medicine, Department of Internal Medicine, Department of Human Genetics, University of Michigan, Ann Arbor (S.K.G.); Department of Medicine, Tulane University School of Medicine, New Orleans, LA (J.H., J.C.); Saw Swee Hock School of Public Health, National University of Singapore and National University Health System (J.L., Y.-Y.T., X.S., E-S.T.); Division of Biostatistics, Washington University School of Medicine, St. Louis, MO (D.C.R.); Department of Medical Genetics (F.-J.T.) and School of Chinese Medicine (C.-H.C., J.-Y.W.), China Medical University Hospital, Taichung, Taiwan; Department of Medicine, Columbia University Medical Center, New York, NY (W.P.); Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston (J.E.H.); Department of Internal Medicine, Ditmanson Medical Foundation, Chiayi Christian Hospital, Taiwan (C.H.L.); Department of Business Administration, National Chung Cheng University, Chia-yi, Taiwan (C.H.L.); Department of Nursing, DaYeh University, Changhua, Taiwan (C.H.L.); Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan (W.-J.L.); State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (D.G.); National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (C.-H.C., J.-Y.W.); Department of Ophthalmology and Visual Science, Khoo Teck Puat Hospital, Singapore, Singapore (N.K.); Medical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (L.J.R.); and Department of Epidemiology and Biostatistics, University of Georgia at Athens, Athens (C.L.); Department of Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan (K.-W.L.).
² From the Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (C.L., J.H., J.Z., T.N.K.); Center for Genome Science, Korea National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Korea (Y.K.K., J.L., S.H., B.-G.H., S.M., B.-J.K.); Genome Institute of Singapore, Agency for Science, Technology and Research (R.D., J.L., Y.-Y.T.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences (H.L., Y.H., Y.W., L.S., X.L.); National Yang-Ming University Hospital, Taipei, Taiwan (I-T.L.); National Yang-Ming University Hospital, Taipei, Taiwan; Singapore Eye Research Institute, Singapore National Eye Center (Y.C., Y.K., Y.Z., N.K., T.Y.W.); Duke-NUS Graduate Medical School, National University of Singapore, (Y.C., N.K., T.Y.W., E-S.T.); Department of Ophthalmology (Y.C., T.Y.W.), Department of Statistics and Applied Probability (Y.-Y.T.), Life Sciences Institute (Y.-Y.T.), NUS Graduate School for Integrative Science and Engineering (Y.-Y.T.), Department of Medicine, National University Health System, Singapore (E-S.T.); MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (M.H., H.H., L.G., Y.H., T.W.); Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taipei, Taiwan (I-T.L., W.H-h.S); School of Medicine, National Yang-Ming University, Taipei, Taiwan (W.H-h.S., K.-W.L.); Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, CA (X.G., J.Y., K.D.T., J.I.R., Y.-d.I.C.); Division of Cardiovascular Medicine, Department of Internal Medicine, Department of Human Genetics, University of Michigan, Ann Arbor (S.K.G.); Department of Medicine, Tulane University School of Medicine, New Orleans, LA (J.H., J.C.); Saw Swee Hock School of Public Health, National University of Singapore and National University Health System (J.L., Y.-Y.T., X.S., E-S.T.); Division of Biostatistics, Washington University School of Medicine, St. Louis, MO (D.C.R.); Department of Medical Genetics (F.-J.T.) and School of Chinese Medicine (C.-H.C., J.-Y.W.), China Medical University Hospital, Taichung, Taiwan; Department of Medicine, Columbia University Medical Center, New York, NY (W.P.); Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston (J.E.H.); Department of Internal Medicine, Ditmanson Medical Foundation, Chiayi Christian Hospital, Taiwan (C.H.L.); Department of Business Administration, National Chung Cheng University, Chia-yi, Taiwan (C.H.L.); Department of Nursing, DaYeh University, Changhua, Taiwan (C.H.L.); Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan (W.-J.L.); State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (D.G.); National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (C.-H.C., J.-Y.W.); Department of Ophthalmology and Visual Science, Khoo Teck Puat Hospital, Singapore, Singapore (N.K.); Medical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (L.J.R.); and Department of Epidemiology and Biostatistics, University of Georgia at Athens, Athens (C.L.); Department of Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan (K.-W.L.). tkelly@tulane.edu.

Abstract

Background: Genome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP.

Methods and results: We conducted genome-wide analysis among 18 422 East Asian participants (stage 1) followed by replication study of ≤46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a P<5.0×10^-8 and 2.5×10^-⁶, respectively, in joint analyses of stage-1 and stage-2 data. We identified 1 novel ARL3 variant, rs4919669 at 10q24.32, influencing LTA systolic BP (stage-1 P=5.03×10^-⁸, stage-2 P=8.64×10^-³, joint P=2.63×10^-⁸) and mean arterial pressure (stage-1 P=3.59×10^-⁹, stage-2 P=2.35×10^-², joint P=2.64×10^-⁸). Three previously reported BP loci (WBP1L, NT5C2, and ATP2B1) were also identified for all BP phenotypes. Gene-based analysis provided the first robust evidence for association of KCNJ11 with LTA systolic BP (stage-1 P=8.55×10^-⁶, stage-2 P=1.62×10^-⁵, joint P=3.28×10^-⁹) and mean arterial pressure (stage-1 P=9.19×10^-⁷, stage-2 P=9.69×10^-⁵, joint P=2.15×10^-⁹) phenotypes. Fourteen genes (TMEM180, ACTR1A, SUFU, ARL3, SFXN2, WBP1L, CYP17A1, C10orf32, C10orf32-ASMT, AS3MT, CNNM2, and NT5C2 at 10q24.32; ATP2B1 at 12q21.33; and NCR3LG1 at 11p15.1) implicated by previous genome-wide association study meta-analyses were also identified. Among the loci identified by the previous genome-wide association study meta-analysis of LTA BP, we transethnically replicated associations of the KCNK3 marker rs1275988 at 2p23.3 with LTA systolic BP and mean arterial pressure phenotypes (P=1.27×10^-⁴ and 3.30×10^-⁴, respectively).

Conclusions: We identified 1 novel variant and 1 novel gene and present the first direct evidence of relevance of the KCNK3 locus for LTA BP among East Asians.

Keywords: arterial pressure; blood pressure; epidemiology; genome-wide association study.

Publication types

Meta-Analysis
Multicenter Study

MeSH terms

Asia, Eastern
Asian People / genetics*
Blood Pressure / genetics*
Female
Genetic Loci*
Genome-Wide Association Study*
Humans
Male
Phenotype*
Polymorphism, Single Nucleotide*

Abstract

Publication types

MeSH terms

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