We conducted a meta-analysis of genome-wide association studies of systolic (SBP) and diastolic (DBP) blood pressure in 19,608 subjects of east Asian ancestry from the AGEN-BP consortium followed up with de novo genotyping (n = 10,518) and further replication (n = 20,247) in east Asian samples. We identified genome-wide significant (P < 5 × 10−8) associations with SBP or DBP, which included variants at four new loci (ST7L-CAPZA1, FIGN-GRB14, ENPEP and NPR3) and a newly discovered variant near TBX3. Among the five newly discovered variants, we obtained significant replication in the independent samples for all of these loci except NPR3. We also confirmed seven loci previously identified in populations of European descent. Moreover, at 12q24.13 near ALDH2, we observed strong association signals (P = 7.9 × 10−31 and P = 1.3 × 10−35 for SBP and DBP, respectively) with ethnic specificity. These findings provide new insights into blood pressure regulation and potential targets for intervention.
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The authors acknowledge the essential role of the Asian Genetic Epidemiology Network (AGEN) in developing and supporting this manuscript. AGEN members include the Cardio-metabolic Genome Epidemiology (CAGE) Network, Genetic Epidemiology Network of Salt-Sensitivity (GenSalt), Korean Association Resource (KARE) Project, Shanghai Hypertension Study, Singapore Malay Eye Survey (SiMES), Singapore Prospective Study (SP2) Program, Suita Study and Taiwan Super Control Study.
CAGE: The CAGE Network Studies were supported by grants for the Core Research for Evolutional Science and Technology (CREST) from the Japan Science Technology Agency; the Program for Promotion of Fundamental Studies in Health Sciences, National Institute of Biomedical Innovation Organization (NIBIO); KAKENHI (Grant-in-Aid for Scientific Research) on Priority Areas 'Applied Genomics' from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and the Grant of National Center for Global Health and Medicine (NCGM).
GenSalt: The Genetic Epidemiology Network of Salt Sensitivity is supported by research grants (U01HL072507, R01HL087263 and R01HL090682) from the National Heart, Lung, and Blood Institute, National Institutes of Health (Bethesda, Maryland, USA). T.N.K. is supported partially by Award Number K12HD043451 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (Bethesda, Maryland, USA).
KARE: KARE and HEXA-shared control studies were supported by grants from Korea Centers for Disease Control & Prevention, Republic of Korea (4845-301, 4851-302, 4851-307).
Shanghai: This work was supported by the Chinese National Key Program for Basic Research (grants 973:2004CB518603, 2006CB503804 and 2009CB521905) and Chinese National High Tech Program (grants 863:2009AA022703 and 2006AA02Z179) and the Ministry of Science and Technology, National Natural Science Foundation (30871361).
SiMES: The Singapore Malay Eye Study (SiMES) was funded by the National Medical Research Council (NMRC 0796/2003 and NMRC/STaR/0003/2008) and the Biomedical Research Council (BMRC, 09/1/35/19/616).
SP2: The Singapore Prospective Study Program (SP2) was funded through grants from the Biomedical Research Council of Singapore (BMRC 05/1/36/19/413 and 03/1/27/18/216) and the National Medical Research Council of Singapore (NMRC/1174/2008). Y.Y.T. acknowledges support from the Singapore National Research Foundation (NRF-RF-2010-05). E.S.T. also receives additional support from the National Medical Research Council through a clinician scientist award (NMRC/CSA/008/2009).
Suita/Ehime Study: The Ehime Study was supported by Grants for Scientific Research (Priority Areas 'Medical Genome Science (Millennium Genome Project)' and 'Applied Genomics') from the Ministry of Education, Culture, Sports, Science and Technology, Japan; a Grants-in-Aid (H15-longevity-005, H17-longevity-003, H16-kenko-001, H18-longevity (kokusai)) from the Ministry of Health, Labor and Welfare, Health and Labor Sciences Research Grants, Japan; a Science and Technology Incubation Program in Advanced Regions, Japan Science and Technology Agency; and the Japan Atherosclerosis Prevention Fund.
Taiwan Super Control Study: This study was supported by Academia Sinica Genomic Medicine Multicenter Study; National Research Program for Genomic Medicine, National Science Council, Taiwan (National Clinical Core, NSC97-3112-B-001-014; and National Genotyping Center, NSC97-3112-B-001-015).
Supplementary Note, Supplementary Figures 1–10 and Supplementary Tables 1–8.