TY - JOUR
T1 - Association of vitamin D status with arterial blood pressure and hypertension risk
T2 - a mendelian randomisation study
AU - Vimaleswaran, Karani S
AU - Cavadino, Alana
AU - Berry, Diane J
AU - Jorde, Rolf
AU - Dieffenbach, Aida Karina
AU - Lu, Chen
AU - Alves, Alexessander Couto
AU - Heerspink, Hiddo J Lambers
AU - Tikkanen, Emmi
AU - Eriksson, Joel
AU - Wong, Andrew
AU - Mangino, Massimo
AU - Jablonski, Kathleen A
AU - Nolte, Ilja M
AU - Houston, Denise K
AU - Ahluwalia, Tarunveer Singh
AU - van der Most, Peter J
AU - Pasko, Dorota
AU - Zgaga, Lina
AU - Thiering, Elisabeth
AU - Vitart, Veronique
AU - Fraser, Ross M
AU - Huffman, Jennifer E
AU - de Boer, Rudolf A
AU - Schöttker, Ben
AU - Saum, Kai-Uwe
AU - McCarthy, Mark I
AU - Dupuis, Josée
AU - Herzig, Karl-Heinz
AU - Sebert, Sylvain
AU - Pouta, Anneli
AU - Laitinen, Jaana
AU - Kleber, Marcus E
AU - Navis, Gerjan
AU - Lorentzon, Mattias
AU - Jameson, Karen
AU - Arden, Nigel
AU - Cooper, Jackie A
AU - Acharya, Jayshree
AU - Hardy, Rebecca
AU - Raitakari, Olli
AU - Ripatti, Samuli
AU - Billings, Liana K
AU - Lahti, Jari
AU - Osmond, Clive
AU - Penninx, Brenda W
AU - Rejnmark, Lars
AU - Lohman, Kurt K
AU - Paternoster, Lavinia
AU - van der Harst, Pim
N1 - Copyright © 2014 Vimaleswaran et al. Open Access article distributed under the terms of CC BY. Published by .. All rights reserved.
PY - 2014/9
Y1 - 2014/9
N2 - BACKGROUND: Low 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.METHODS: In 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.FINDINGS: In 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).INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.FUNDING: British Heart Foundation, UK Medical Research Council, and Academy of Finland.
AB - BACKGROUND: Low 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.METHODS: In 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.FINDINGS: In 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).INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.FUNDING: British Heart Foundation, UK Medical Research Council, and Academy of Finland.
KW - Adult
KW - Body Mass Index
KW - Cholestanetriol 26-Monooxygenase/genetics
KW - Cytochrome P450 Family 2
KW - Female
KW - Genetic Predisposition to Disease
KW - Humans
KW - Hypertension/blood
KW - Male
KW - Mendelian Randomization Analysis
KW - Middle Aged
KW - Oxidoreductases Acting on CH-CH Group Donors/genetics
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - Randomized Controlled Trials as Topic
KW - Vitamin D/administration & dosage
KW - Vitamin D Deficiency/blood
U2 - 10.1016/S2213-8587(14)70113-5
DO - 10.1016/S2213-8587(14)70113-5
M3 - Article
C2 - 24974252
SN - 2213-8587
VL - 2
SP - 719
EP - 729
JO - The Lancet Diabetes & Endocrinology
JF - The Lancet Diabetes & Endocrinology
IS - 9
ER -