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

Circ Cardiovasc Genet

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.).

Published: April 2017

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 <5.0×10 and 2.5×10, respectively, in joint analyses of stage-1 and stage-2 data. We identified 1 novel variant, rs4919669 at 10q24.32, influencing LTA systolic BP (stage-1 =5.03×10, stage-2 =8.64×10, joint =2.63×10) and mean arterial pressure (stage-1 =3.59×10, stage-2 =2.35×10, joint =2.64×10). Three previously reported BP loci (, , and ) were also identified for all BP phenotypes. Gene-based analysis provided the first robust evidence for association of with LTA systolic BP (stage-1 =8.55×10, stage-2 =1.62×10, joint =3.28×10) and mean arterial pressure (stage-1 =9.19×10, stage-2 =9.69×10, joint =2.15×10) phenotypes. Fourteen genes (, , , , , , , , -, , , and at 10q24.32; at 12q21.33; and 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 marker rs1275988 at 2p23.3 with LTA systolic BP and mean arterial pressure phenotypes (=1.27×10 and 3.30×10, respectively).

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

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704911	PMC
http://dx.doi.org/10.1161/CIRCGENETICS.116.001527	DOI Listing

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