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Journal Article

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study


  1. Karani S. Vimaleswaran
  2. Alana Cavadino
  3. Diane J. Berry
  4. Rolf Jorde
  5. Aida Karina Dieffenbach
  6. Chen Lu
  7. Alexessander Couto Alves
  8. Hiddo J. Lambers Heerspink
  9. Emmi Tikkanen
  10. Joel Eriksson
  11. Andrew Wong
  12. Massimo Mangino
  13. Kathleen A. Jablonski
  14. Ilja M. Nolte
  15. Denise K. Houston
  16. Tarunveer Singh Ahluwalia
  17. Peter J. van der Most
  18. Dorota Pasko
  19. Lina Zgaga
  20. Elisabeth Thiering
  21. Veronique Vitart
  22. Ross M. Fraser
  23. Jennifer E. Huffman
  24. Rudolf A. de Boer
  25. Ben Schöttker
  26. Kai-Uwe Saum
  27. Mark I. McCarthy
  28. Josée Dupuis
  29. Karl-Heinz Herzig
  30. Sylvain Sebert
  31. Anneli Pouta
  32. Jaana Laitinen
  33. Marcus E. Kleber
  34. Gerjan Navis
  35. Mattias Lorentzon
  36. Karen Jameson
  37. Nigel Arden
  38. Jackie A. Cooper
  39. Jayshree Acharya
  40. Rebecca Hardy
  41. Olli Raitakari
  42. Samuli Ripatti
  43. Liana K. Billings
  44. Jari Lahti
  45. Clive Osmond
  46. Brenda W. Penninx
  47. Lars Rejnmark
  48. Kurt K. Lohman
  49. Lavinia Paternoster
  50. Ronald P. Stolk
  51. Dena G. Hernandez
  52. Liisa Byberg
  53. Emil Hagström
  54. Håkan Melhus
  55. Erik Ingelsson
  56. Dan Mellström
  57. Östen Ljunggren
  58. Ioanna Tzoulaki
  59. Stela McLachlan
  60. Evropi Theodoratou
  61. Carla M. T. Tiesler
  62. Antti Jula
  63. Pau Navarro
  64. Alan F. Wright
  65. Ozren Polasek
  66. James F. Wilson
  67. Igor Rudan
  68. Veikko Salomaa
  69. Joachim Heinrich
  70. Harry Campbell
  71. Jacqueline F. Price
  72. Magnus Karlsson
  73. Lars Lind
  74. Karl Michaëlsson
  75. Stefania Bandinelli
  76. Timothy M. Frayling
  77. Catharina A. Hartman
  78. Thorkild I. A. Sørensen
  79. Stephen B. Kritchevsky
  80. Bente Lomholt Langdahl
  81. Johan G. Eriksson
  82. Jose C. Florez
  83. Tim D. Spector
  84. Terho Lehtimäki
  85. Diana Kuh
  86. Steve E. Humphries
  87. Cyrus Cooper
  88. Claes Ohlsson
  89. Winfried März
  90. Martin H. de Borst
  91. Meena Kumari
  92. Mika Kivimaki
  93. Thomas J. Wang
  94. Chris Power
  95. Hermann Brenner
  96. Guri Grimnes
  97. Pim van der Harst
  98. Harold Snieder
  99. Aroon D. Hingorani
  100. Stefan Pilz
  101. John C. Whittaker
  102. Marjo-Riitta Järvelin
  103. Elina Hyppönen

Publication date

Sep 2014


plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with
high arterial blood pressure and hypertension risk, but whether this
association is causal is unknown. We used a mendelian randomisation
approach to test whether 25(OH)D concentration is causally associated
with blood pressure and hypertension risk.MethodsIn
this mendelian randomisation study, we generated an allele score
(25[OH]D synthesis score) based on variants of genes that affect 25(OH)D
synthesis or substrate availability (CYP2R1 and DHCR7),
which we used as a proxy for 25(OH)D concentration. We meta-analysed
data for up to 108 173 individuals from 35 studies in the D-CarDia
collaboration to investigate associations between the allele score and
blood pressure measurements. We complemented these analyses with
previously published summary statistics from the International
Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging
Research in Genomic Epidemiology (CHARGE) consortium, and the Global
Blood Pressure Genetics (Global BPGen) consortium.FindingsIn
phenotypic analyses (up to n=49 363), increased 25(OH)D concentration
was associated with decreased systolic blood pressure (β per 10%
increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds
of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but
not with decreased diastolic blood pressure (β per 10% increase, −0·02
mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined
data from D-CarDia and the ICBP (n=146 581, after exclusion of
overlapping studies), each 25(OH)D-increasing allele of the synthesis
score was associated with a change of −0·10 mm Hg in systolic blood
pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in
diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and
consortia data for hypertension were meta-analysed together (n=142 255),
the synthesis score was associated with a reduced odds of hypertension
(OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable
analysis, each 10% increase in genetically instrumented 25(OH)D
concentration was associated with a change of −0·29 mm Hg in diastolic
blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in
systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased
odds of hypertension (OR 0·92, 0·87–0·97; p=0·002).InterpretationIncreased
plasma concentrations of 25(OH)D might reduce the risk of hypertension.
This finding warrants further investigation in an independent,
similarly powered study.

Published in

The Lancet Diabetes and Endocrinology

Volume and page numbers

2 , 719 -729





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