Author
Vimaleswaran, Kerani S.;
Cavadino, Alana;
Berry, Diane J.;
Jorde, Rolf;
Grimnes, Guri;
Dieffenbach, Aida Karina;
Lu, Chen;
Alves, Alexessander Couto;
Heerspink, Hiddo J. Lambers;
Tikkanen, Emmi;
Eriksson, Joel;
Wong, Andrew;
Mangino, Massimo;
Jablonski, Kathleen A.;
Nolte, Ilja M.;
Houston, Denise K.;
Ahluwalia, Tarunveer Singh;
van der Most, Peter J.;
Pasko, Dorota;
Zgaga, Lina;
Thiering, Elisabeth;
Schöttker, B;
Saum, KU;
Brenner, H;
Järvelin, MR;
Tzoulaki, I;
Snieder, H;
Stolk, RP;
Hartman, CA;
de Boer, RA;
van der Harst, P;
Navis, G;
de Borst, MH;
Lorentzon, M;
Mellström, D;
Ohlsson, C;
Hardy, R;
Kuh, D;
Cooper, JA;
Acharya, J;
Humphries, SE;
Hingorani, AD;
Kumari, M;
Kivimaki, M;
Spector, TD;
Kritchevsky, SB;
Lohman, KK;
Sørensen, TIA;
Frayling, TM;
Campbell, H;
Theodoratou, E;
Fraser, RM;
Wilson, JF;
Rudan, I;
Price, JF;
McLachlan, S;
Vitart, V;
Navarro, P;
Huffman, JE;
Hayward, C;
Wright, AF;
Tiesler, CMT;
Heinrich, J;
McCarthy, MI;
Ingelsson, E;
Arden, N;
Cooper, C;
Dupuis, J;
Herzig, KH;
Sebert, S;
Pouta, A;
Laitinen, J;
Kleber, ME;
März, W;
Jameson, K;
Osmond, C;
Raitakari, O;
Ripatti, S;
Lahti, J;
Eriksson, JG;
Penninx, BW;
Billings, LK;
Florez, JC;
Rejnmark, L;
Langdahl, BL;
Paternoster, L;
Hernandez, DG;
Byberg, L;
Michaelsson, K;
Hagström, E;
Melhus, H;
Ljunggren, O;
Lind, L;
Jula, A;
Polasek, O;
Salomaa, V;
Karlsson, M;
Bandinelli, S;
Lehtimäki, T;
Wang, TJ;
Pilz, S;
Whittaker, JC
Abstract
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 aff ect 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 fi nding
warrants further investigation in an independent, similarly powered study.
Publisher
Elsevier
Citation
Vimaleswaran, Cavadino A, Berry, Jorde r, Grimnes G, Dieffenbach AK, Lu, Alves AC, Heerspink, Tikkanen E, Eriksson J, Wong A, Mangino M, Jablonski, Nolte, Houston, Ahluwalia TS, van der Most, Pasko D, Zgaga L, Thiering, Schöttker B, Saum, Brenner H, Järvelin, Tzoulaki I, Snieder H, Stolk R, Hartman, de Boer R, van der Harst P, Navis G, de Borst, Lorentzon M, Mellström, Ohlsson C, Hardy R, Kuh D, Cooper J, Acharya, Humphries S, Hingorani A, Kumari M, Kivimaki M, Spector T, Kritchevsky S, Lohman K, Sørensen, Frayling T, Campbell H, Theodoratou, Fraser R, Wilson J, Rudan I, Price J, McLachlan S, Vitart V, Navarro P, Huffman J, Hayward C, Wright A, Tiesler C, Heinrich J, McCarthy M, Ingelsson E, Arden, Cooper C, Dupuis J, Herzig K, Sebert, Pouta A, Laitinen J, Kleber M, März, Jameson K, Osmond, Raitakari O, Ripatti S, Lahti J, Eriksson J, Penninx B, Billings, Florez J, Rejnmark L, Langdahl B, Paternoster L, Hernandez D, Byberg L, Michaelsson K, Hagström, Melhus H, Ljunggren O, Lind L, Jula A, Polasek O, Salomaa V, Karlsson M, Bandinelli S, Lehtimäki, Wang T, Pilz, Whittaker. Association of vitamin D status with arterial blood pressure and hypertension risk: A mendelian randomisation study. The Lancet Diabetes and Endocrinology. 2014;2(9):719-729
English
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