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Journal Article

New blood pressure–associated loci identified in meta-analyses of 475 000 individuals

Authors

  1. Aldi T. Kraja
  2. James P. Cook
  3. Helen R. Warren
  4. Praveen Surendran
  5. Chunyu Liu
  6. Evangelos Evangelou
  7. Alisa K. Manning
  8. Niels Grarup
  9. Fotios Drenos
  10. Xueling Sim
  11. Albert Vernon Smith
  12. Najaf Amin
  13. Alexandra I.F. Blakemore
  14. Jette Bork-Jensen
  15. Ivan Brandslund
  16. Aliki-Eleni Farmaki
  17. Cristiano Fava
  18. Teresa Ferreira
  19. Karl-Heinz Herzig
  20. Ayush Giri
  21. Franco Giulianini
  22. Megan L. Grove
  23. Xiuqing Guo
  24. Sarah E. Harris
  25. Christian T. Have
  26. Aki S. Havulinna
  27. He Zhang
  28. Marit E. Jørgensen
  29. AnneMari Käräjämäki
  30. Charles Kooperberg
  31. Allan Linneberg
  32. Louis Little
  33. Yongmei Liu
  34. Lori L. Bonnycastle
  35. Yingchang Lu
  36. Reedik Mägi
  37. Anubha Mahajan
  38. Giovanni Malerba
  39. Riccardo E. Marioni
  40. Hao Mei
  41. Cristina Menni
  42. Alanna C. Morrison
  43. Sandosh Padmanabhan
  44. Walter Palmas
  45. Alaitz Poveda
  46. Rainer Rauramaa
  47. Nigel William Rayner
  48. Muhammad Riaz
  49. Ken Rice
  50. Melissa A. Richard
  51. Jennifer A. Smith
  52. Lorraine Southam
  53. Alena Stančáková
  54. Kathleen E. Stirrups
  55. Vinicius Tragante
  56. Tiinamaija Tuomi
  57. Ioanna Tzoulaki
  58. Tibor V. Varga
  59. Stefan Weiss
  60. Andrianos M. Yiorkas
  61. Robin Young
  62. Weihua Zhang
  63. Michael R. Barnes
  64. Claudia P. Cabrera
  65. He Gao
  66. Michael Boehnke
  67. Eric Boerwinkle
  68. John C. Chambers
  69. John M. Connell
  70. Cramer K. Christensen
  71. Rudolf A. de Boer
  72. Ian J. Deary
  73. George Dedoussis
  74. Panos Deloukas
  75. Anna F. Dominiczak
  76. Marcus Dörr
  77. Roby Joehanes
  78. Todd L. Edwards
  79. Tonu Esko
  80. Myriam Fornage
  81. Nora Franceschini
  82. Paul W. Franks
  83. Giovanni Gambaro
  84. Leif Groop
  85. Göran Hallmans
  86. Torben Hansen
  87. Caroline Hayward
  88. Oksa Heikki
  89. Erik Ingelsson
  90. Jaakko Tuomilehto
  91. Marjo-Riitta Jarvelin
  92. Sharon L.R. Kardia
  93. Fredrik Karpe
  94. Jaspal S. Kooner
  95. Timo A. Lakka
  96. Claudia Langenberg
  97. Lars Lind
  98. Ruth J. F. Loos
  99. Markku Laakso
  100. Mark I. McCarthy
  101. Olle Melander
  102. Karen L. Mohlke
  103. Andrew P. Morris
  104. Colin N. A. Palmer
  105. Oluf Pedersen
  106. Ozren Polasek
  107. Neil R. Poulter
  108. Michael A. Province
  109. Bruce M. Psaty
  110. Paul M. Ridker
  111. Jerome I. Rotter
  112. Igor Rudan
  113. Veikko Salomaa
  114. Nilesh J. Samani
  115. Peter J. Sever
  116. Tea Skaaby
  117. Jeanette M. Stafford
  118. John M. Starr
  119. Pim van der Harst
  120. Peter van der Meer
  121. Cornelia M. van Duijn
  122. Anne-Claire Vergnaud
  123. Vilmundur Gudnason
  124. Nicholas J. Wareham
  125. James G. Wilson
  126. Cristen J. Willer
  127. Daniel R. Witte
  128. Eleftheria Zeggini
  129. Danish Saleheen
  130. Adam S. Butterworth
  131. John Danesh
  132. Folkert W. Asselbergs
  133. Louise V. Wain
  134. Georg B. Ehret
  135. Daniel I. Chasman
  136. Mark J. Caulfield
  137. Paul Elliott
  138. Cecilia M. Lindgren
  139. Daniel Levy
  140. Christopher Newton-Cheh
  141. Patricia B. Munroe
  142. Joanna M. M. Howson

Publication date

Oct 2017

Summary

Background—Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results—Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant (P<5×10−8) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions—We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.

Published in

Circulation: Cardiovascular Genetics

Volume

10:e001778

DOI

http://dx.doi.org/10.1161/CIRCGENETICS.117.001778

ISSN

16

Subjects

Medicine, Science And Technology, Health, Biology, and Genetics

Notes

Not held in Hilary Doughty Research Library - bibliographic reference only

#524653


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