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

Vimaleswaran, KS and Cavadino, A and Berry, DJ and Power, C and Hyppönen, E and Jorde, R and Grimnes, G and Dieff enbach, AK and Schöttker, B and Saum, KU and Brenner, H and Lu, C and Järvelin, MR and Tzoulaki, I and Heerspink, HJL and Nolte, IM and Snieder, H and van der Most, PJ and Stolk, RP and Hartman, CA and de Boer, RA and van der Harst, P and Navis, G and de Borst, MH and Tikkanen, E and Eriksson, J and Lorentzon, M and Mellström, D and Ohlsson, C and Wong, A and Hardy, R and Kuh, D and Cooper, JA and Acharya, J and Humphries, SE and Hingorani, AD and Kumari, M and Kivimaki, M and Mangino, M and Spector, TD and Jablonski, KA and Houston, DK and Kritchevsky, SB and Lohman, KK and Ahluwalia, TS and Sørensen, TIA and Pasko, D and Frayling, TM and Zgaga, L and Campbell, H and Theodoratou, E and Fraser, RM and Wilson, JF and Rudan, I and Price, JF and McLachlan, S and Vitart, V and Navarro, P and Huffman, JE and Hayward, C and Wright, AF and Thiering, E and Tiesler, CMT and Heinrich, J and McCarthy, MI and Ingelsson, E and Cooper, C and Arden, N and Dupuis, J (2014) 'Association of vitamin D status with arterial blood pressure and hypertension risk: A mendelian randomisation study.' The Lancet Diabetes and Endocrinology, 2 (9). 719 - 729. ISSN 2213-8587

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Abstract

© 2014 Vimaleswaran et al. Open Access article distributed under the terms of CC BY. 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.

Item Type: Article
Subjects: H Social Sciences > HA Statistics
R Medicine > R Medicine (General)
Divisions: Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Jim Jamieson
Date Deposited: 06 Feb 2015 14:13
Last Modified: 17 Aug 2017 17:40
URI: http://repository.essex.ac.uk/id/eprint/12672

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