☆ 4.8 Article

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

NATURE GENETICS (2015)

Get Full Text
Add to Collection

Journal

NATURE GENETICS
Volume 47, Issue 11, Pages 1282-+

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3405

Keywords

-

Categories

Genetics & Heredity

Funding

  1. Grants for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan [24390084, 21390099, 20390185, 22390186, 24591060, 25253059, 25461127]
  2. Science and Technology Incubation Program in Advanced Regions, Japanese Science and Technology Agency
  3. Japanese Atherosclerosis Prevention Fund
  4. Takeda Medical Research Foundation
  5. National Cardiovascular Research Grants
  6. US National Institutes of Health (NIH) - National Institute of Diabetes and Digestive and Kidney Diseases [R01DK082766]
  7. National Human Genome Research Institute [NOT-HG-11-009]
  8. VPR bridge grant from the University of Oklahoma Health Sciences Center
  9. BBMRI-NL
  10. Netherlands Organization for Scientific Research (NWO project) [184.021.007]
  11. Ministry of Education, Culture, Sports, Science and Technology of Japan
  12. Japanese Society for the Promotion of Science
  13. grants for Core Research for Evolutional Science and Technology (CREST) from the Japanese Science and Technology Agency
  14. Program for the Promotion of Fundamental Studies in Health Sciences, National Institute of Biomedical Innovation Organization (NIBIO)
  15. KAKENHI on Priority Area 'Applied Genomics' from the Ministry of Education, Culture, Sports, Science and Technology of Japan
  16. National Center for Global Health and Medicine
  17. Okinaga Scholarship
  18. Grants for International Health Research from the Ministry of Health, Labour and Welfare of Japan [17C-1, 20S-6]
  19. National Center for Global Health and Medicine [22S-10, 25S-1]
  20. Manpei Suzuki Diabetes Foundation
  21. Italian Ministry of Universities (Interomics Flag project) [FIRB-RBNE08NKH7]
  22. Assessorato Ricerca Regione Campania
  23. Fondazione con il SUD [2011-PDR-13]
  24. Fondazione Banco di Napoli
  25. National Institutes of Health [DK078150, TW05596, HL085144, TW008288]
  26. Novo Nordisk
  27. Swedish Research Council
  28. Pahlssons Foundation
  29. Swedish Heart Lung Foundation
  30. Skane Regional Health Authority
  31. Estonian government [SF0180142s08]
  32. Center of Excellence in Genomics (EXCEGEN)
  33. University of Tartu [SP1GVARENG]
  34. Competitive Research Funding from Tampere University Hospital [9M048, 9N035]
  35. Finnish Cultural Foundation
  36. Finnish Foundation for Cardiovascular Research
  37. Emil Aaltonen Foundation, Finland
  38. Tampere Tuberculosis Foundation
  39. US NIH [R01CA107431, P42ES10349, 2R01LM010098, NCI RO1CA55069, R35CA53890, R01CA80205, R01CA144034, RO1CA82729, UM1CA173640, R37CA70867]
  40. National Heart, Lung, and Blood Institute [P01HL098055, P01HL076491, R01HL103866, P20HL113452, R01HL103931]
  41. National Institute of Environmental Health Sciences [R01ES021801]
  42. National Heart, Lung, and Blood Institute, US NIH [U01HL072507, R01HL087263, R01HL090682]
  43. Velux Foundation
  44. Danish Medical Research Council
  45. Danish Agency for Science, Technology and Innovation
  46. Aase and Ejner Danielsens Foundation
  47. ALK-Abello (Horsholm, Denmark)
  48. Timber Merchant Vilhelm Bangs Foundation
  49. MEKOS Laboratories Denmark
  50. Research Centre for Prevention and Health
  51. Capital Region of Denmark
  52. Lundbeck Foundation
  53. Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp)
  54. Novo Nordisk Foundation
  55. Korean Centers for Disease Control and Prevention [4845-301, 4851-302, 4851-307]
  56. Korean National Institute of Health, Republic of Korea [2012-N73002-00]
  57. UK Medical Research Council
  58. British Heart Foundation
  59. Merck Co.
  60. Roche Vitamins, Ltd.
  61. University of Oxford
  62. Centre National de Genotypage from Merck Co.
  63. Oxford British Heart Foundation Centre of Research Excellence
  64. British Heart Foundation [FS/14/55/30806, RG/07/008/23674]
  65. GENDINOB project
  66. Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme [NMRC/TCR/012-NUHS/2014]
  67. Singapore Institute for Clinical Sciences, A*STAR, Singapore
  68. Compagnia di San Paolo (Torino, Italy)
  69. Fondazione Cariplo, Italy
  70. Ministry of Health, Ricerca Finalizzata
  71. CCM
  72. Telethon, Italy
  73. Danish Research Council
  74. Danish Centre for Health Technology Assessment
  75. Research Foundation of Copenhagen County
  76. Ministry of Internal Affairs and Health
  77. Danish Heart Foundation
  78. Danish Pharmaceutical Association
  79. Augustinus Foundation
  80. Ib Henriksen Foundation
  81. Becket Foundation
  82. Danish Diabetes Association
  83. European Union (Sixth Framework Programme of the European Community) [LSHM-CT-2006-037197]
  84. Ministry of Education, Culture, Sports, Science and Technology of Japan [21390099, 20390185, 19659163, 16790336, 12204008, 15790293, 16590433, 17790381, 18390192, 18590265, 18590587, 18590811, 19590929, 19650188, 19790423, 17390186, 20390184, 21390223]
  85. Ministry of Health, Labor and Welfare of Japan [H15-Longevity-005, H17-Longevity-003, H16-Kenko-001, H18-Longevity(kokusai), H11-Longevity-020, H17-Kenkou-007, H17-Pharmaco-common-003, H18-Junkankitou[Seishuu]-Ippan-012, H20-Junkankitou[Seishuu]-Ippan-009, 013]
  86. Health and Labor Sciences Research Grants, Japan
  87. Science and Technology Incubation Program in Advanced Regions
  88. Japanese Science and Technology Agency
  89. Japanese Society for the Promotion of Science [16.54041, 18.54042, 19.7152, 20.7198, 20.7477, 20.54043]
  90. Health Science Research Grants and Medical Technology Evaluation Research Grants from the Ministry of Health, Labour and Welfare of Japan
  91. Uehara Memorial Foundation
  92. Biomedical Innovation Grants
  93. Japanese Research Foundation for Clinical Pharmacology
  94. Helmholtz Zentrum Munchen-German Research Center for Environmental Health
  95. German Federal Ministry of Education and Research (BMBF)
  96. Federal Ministry of Health
  97. Munich Center of Health Sciences (MC Health), LMUinnovativ
  98. German-Israeli Foundation for Scientific Research and Development
  99. European Union [305280, 279143, 201668, 305739, LSHM-CT-2004-503485]
  100. Helmholtz-Russia Joint Research Group (HRJRG) [310]
  101. German Center for Diabetes Research (DZD)
  102. EU [602936]
  103. BMBF e:Med project e:AtheroSysMed-Systems Medicine of Myocardial Infarction and Stroke
  104. UK Biotechnology and Biological Sciences Research Council (BBSRC)
  105. Royal Society
  106. Chief Scientist Office of the Scottish government
  107. BBSRC
  108. Age UK (The Disconnected Mind project)
  109. Netherlands Organization for Scientific Research (NWO) [175.010.2007.006, 184021007]
  110. Economic Structure-Enhancing Fund (FES) of the Dutch government
  111. Ministry of Economic Affairs
  112. Ministry of Education, Culture and Science
  113. Ministry for Health, Welfare and Sports
  114. Northern Netherlands Collaboration of Provinces (SNN)
  115. province of Groningen, University Medical Center Groningen
  116. University of Groningen
  117. Dutch Kidney Foundation
  118. Dutch Diabetes Research Foundation
  119. NIHR Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust
  120. Medical Research Council, UK [G0601966, G0700931, G0500539, G0600331, G0902037]
  121. Wellcome Trust [084723/Z/08/Z]
  122. NIHR [RP-PG-0407-10371]
  123. Action on Hearing Loss [G51]
  124. INTERREG IV Oberrhein Program (Genetic Mechanisms of Cardiovascular Diseases) [A28]
  125. European Regional Development Fund (ERDF)
  126. Wissenschaftsoffensive TMO
  127. Academy of Finland (Center of Excellence in Complex Disease Genetics) [104781, 120315, 129269]
  128. University Hospital Oulu, Biocenter
  129. University of Oulu, Finland [75617]
  130. European Commission [QLG1-CT-2000-01643, 223004]
  131. National Heart, Lung, and Blood Institute through the STAMPEED program [5R01HL087679-02, 1RL1MH083268-01]
  132. US NIH/National Institute of Mental Health [5R01MH63706:02]
  133. ENGAGE project
  134. Academy of Finland [286284, 134309, 126925, 121584, 124282, 129378, 117787, 41071]
  135. Biocentrum Helsinki
  136. German Ministry of Education and Research (BMBF) through the National Genome Research Network (NGFN)
  137. Ministry of Science, Commerce and Transportation of the state of Schleswig-Holstein
  138. German Ministry of Education and Research [01EY1103]
  139. Dutch Kidney Foundation [E033]
  140. European Union project grant GENECURE [FP-6 LSHM CT 2006 037697]
  141. Netherlands Organization for Health Research and Development (NWO-Groot grant) [175.010.2007.006]
  142. Netherlands Organization for Health Research and Development (NWO VENI grant) [916.761.70]
  143. Netherlands Organization for Health Research and Development (ZonMw grant) [90.700.441]
  144. Dutch Interuniversity Cardiology Institute Netherlands (ICIN)
  145. Pfizer
  146. Bristol-Myers-Squibb
  147. Netherlands Heart Foundation [2001 D 032]
  148. Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant) [050-060-810]
  149. Erasmus Medical Center
  150. Erasmus University
  151. Netherlands Organization for Health Research and Development (ZonMw)
  152. Research Institute for Diseases in the Elderly (RIDE)
  153. European Commission (DG XII)
  154. municipality of Rotterdam
  155. Genetic Laboratory of the Department of Internal Medicine, Erasmus Medical Center
  156. Biomedical Research Council of Singapore [08/1/35/19/550, 09/1/35/19/616]
  157. NMRC, Singapore [STaR/0003/2008, CG/SERI/2010, NMRC/1270/2010, 0796/2003, IRG07nov013, IRG09nov014]
  158. Genetic and Environmental Determinants of Type 2 Diabetes in Chinese Singaporeans, grant from the US NIH [R01DK080720]
  159. NMRC of Singapore
  160. Genome Institute of Singapore
  161. A*STAR, Singapore
  162. US NIH/National Cancer Institute [R35CA53890, R01CA80205, R01CA144034, RO1CA55069]
  163. NUS-HUJ CREATE Programme of the National Research Foundation, Singapore [370062002]
  164. Biomedical Research Council of Singapore (A*STAR, Singapore)
  165. Dutch government [NWO 184.021.007]
  166. National Natural Science Foundation of China [81172761]
  167. Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions
  168. Yong Loo Lin School of Medicine
  169. National University Health System
  170. Life Sciences Institute of the National University of Singapore
  171. National Research Foundation of Singapore [NRF-RF-2010-05]
  172. Biomedical Research Council of Singapore (under the individual research grants scheme)
  173. Chinese National Key Program for Basic Research (973) [2004CB518603, 2006CB503804, 2009CB521905]
  174. Chinese National High-Tech Program (863) [2009AA022703, 2006AA022179]
  175. Ministry of Science and Technology, National Natural Science Foundation of China [30871361]
  176. Academia Sinica Genomic Medicine Multicenter Study, Taiwan [40-05-GMM]
  177. Stroke Association
  178. National Institute on Aging [5RO1AG13196]
  179. Agency for Health Care Policy Research [HS06516]
  180. John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socio-Economic Status and Health
  181. Social Insurance Institution of Finland
  182. Kuopio, Tampere and Turku University Hospital Medical Funds [X51001]
  183. Juho Vainio Foundation
  184. Paavo Nurmi Foundation
  185. Finnish Foundation of Cardiovascular Research
  186. Emil Aaltonen Foundation
  187. Yrjo Jahnsson Foundation
  188. [RR20649]
  189. [ES10126]
  190. [DK56350]
  191. [HEALTH-F4-2007-201413]
  192. BBSRC [BB/F019394/1] Funding Source: UKRI
  193. MRC [G0802782, G0800270, G0600331, MC_UU_12015/1, G0700931, MR/L01341X/1, G0902037, MR/K002414/1, MC_UU_12013/1, MR/K013351/1, MR/L003120/1, G0601966] Funding Source: UKRI
  194. Biotechnology and Biological Sciences Research Council [BB/F019394/1] Funding Source: researchfish
  195. British Heart Foundation [RG/07/008/23674, FS/14/55/30806, RG/13/2/30098, RG/08/014/24067] Funding Source: researchfish
  196. Chief Scientist Office [CZB/4/505, ETM/55] Funding Source: researchfish
  197. Medical Research Council [MR/L01341X/1, MC_U106179471, G0600331, MR/M012638/1, MR/K002414/1, G0601966, MR/K026992/1, MR/K013351/1, G0700931, MC_UU_12015/1, G0800270, G0802782, G0902037, 1241993, MR/L003120/1, MC_UU_12013/1] Funding Source: researchfish
  198. National Institute for Health Research [NF-SI-0611-10136, NF-SI-0512-10165, NF-SI-0611-10170] Funding Source: researchfish
  199. RNID [G51] Funding Source: researchfish
  200. Korea Health Promotion Institute [2012-N73002-00] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
  201. Grants-in-Aid for Scientific Research [25670353, 15K05577, 25461127, 24390084, 22390186, 12204008, 18590265, 24591060, 17790381, 19659163, 19790423, 20390185, 19650188, 221S0002, 15790293, 25253059, 21390099, 18590811, 17390186, 20390184, 16790336, 18590587, 21390223, 16590433, 19590929] Funding Source: KAKEN

Ask authors/readers for more resources

Protocol

Community support

Reagent

Community support

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 x 10(-11) to 5.0 x 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 x 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available
Webinars Posters Questions Hubs Funding Journals Papers Connect Collections Reviewers About Us FAQs Mobile App Privacy Policy Terms of Use
© Peeref 2019-2024. All rights reserved.