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

Karani S Vimaleswaran; Alana Cavadino; Diane J Berry; Rolf Jorde; Aida Karina Dieffenbach; Chen Lu; Alexessander Couto Alves; Hiddo J Lambers Heerspink; Emmi Tikkanen; Joel Eriksson; Andrew Wong; Massimo Mangino; Kathleen A Jablonski; Ilja M Nolte; Denise K Houston; Tarun Veer Singh Ahluwalia; Peter J van der Most; Dorota Pasko; Lina Zgaga; Elisabeth Thiering; Veronique Vitart; Ross M Fraser; Jennifer E Huffman; Rudolf A de Boer; Ben Schöttker; Kai-Uwe Saum; Mark I McCarthy; Josée Dupuis; Karl-Heinz Herzig; Sylvain Sebert; Anneli Pouta; Jaana Laitinen; Marcus E Kleber; Gerjan Navis; Mattias Lorentzon; Karen Jameson; Nigel Arden; Jackie A Cooper; Jayshree Acharya; Rebecca Hardy; Olli Raitakari; Samuli Ripatti; Liana K Billings; Jari Lahti; Clive Osmond; Brenda W Penninx; Lars Rejnmark; Kurt K Lohman; Lavinia Paternoster; Thorkild I A Sørensen; LifeLines Cohort Study investigators

doi:10.1016/S2213-8587(14)70113-5

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

Karani S Vimaleswaran, Alana Cavadino, Diane J Berry, Rolf Jorde, Aida Karina Dieffenbach, Chen Lu, Alexessander Couto Alves, Hiddo J Lambers Heerspink, Emmi Tikkanen, Joel Eriksson, Andrew Wong, Massimo Mangino, Kathleen A Jablonski, Ilja M Nolte, Denise K Houston, Tarun Veer Singh Ahluwalia, Peter J van der Most, Dorota Pasko, Lina Zgaga, Elisabeth ThieringVeronique Vitart, Ross M Fraser, Jennifer E Huffman, Rudolf A de Boer, Ben Schöttker, Kai-Uwe Saum, Mark I McCarthy, Josée Dupuis, Karl-Heinz Herzig, Sylvain Sebert, Anneli Pouta, Jaana Laitinen, Marcus E Kleber, Gerjan Navis, Mattias Lorentzon, Karen Jameson, Nigel Arden, Jackie A Cooper, Jayshree Acharya, Rebecca Hardy, Olli Raitakari, Samuli Ripatti, Liana K Billings, Jari Lahti, Clive Osmond, Brenda W Penninx, Lars Rejnmark, Kurt K Lohman, Lavinia Paternoster, Thorkild I A Sørensen, LifeLines Cohort Study investigators

Department of Public Health

229 Citations (Scopus)

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 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.

Original language	English
Journal	The Lancet Diabetes & Endocrinology
Volume	2
Issue number	9
Pages (from-to)	719-729
Number of pages	11
ISSN	2213-8587
DOIs	https://doi.org/10.1016/S2213-8587(14)70113-5
Publication status	Published - 1 Sept 2014

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Vimaleswaran, K. S., Cavadino, A., Berry, D. J., Jorde, R., Dieffenbach, A. K., Lu, C., Alves, A. C., Heerspink, H. J. L., Tikkanen, E., Eriksson, J., Wong, A., Mangino, M., Jablonski, K. A., Nolte, I. M., Houston, D. K., Ahluwalia, T. V. S., van der Most, P. J., Pasko, D., Zgaga, L., ... LifeLines Cohort Study investigators (2014). Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. The Lancet Diabetes & Endocrinology, 2(9), 719-729. https://doi.org/10.1016/S2213-8587(14)70113-5

Vimaleswaran, KS, Cavadino, A, Berry, DJ, Jorde, R, Dieffenbach, AK, Lu, C, Alves, AC, Heerspink, HJL, Tikkanen, E, Eriksson, J, Wong, A, Mangino, M, Jablonski, KA, Nolte, IM, Houston, DK, Ahluwalia, TVS, van der Most, PJ, Pasko, D, Zgaga, L, Thiering, E, Vitart, V, Fraser, RM, Huffman, JE, de Boer, RA, Schöttker, B, Saum, K-U, McCarthy, MI, Dupuis, J, Herzig, K-H, Sebert, S, Pouta, A, Laitinen, J, Kleber, ME, Navis, G, Lorentzon, M, Jameson, K, Arden, N, Cooper, JA, Acharya, J, Hardy, R, Raitakari, O, Ripatti, S, Billings, LK, Lahti, J, Osmond, C, Penninx, BW, Rejnmark, L, Lohman, KK, Paternoster, L, Sørensen, TIA & LifeLines Cohort Study investigators 2014, 'Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study', The Lancet Diabetes & Endocrinology, vol. 2, no. 9, pp. 719-729. https://doi.org/10.1016/S2213-8587(14)70113-5

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

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 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.",

author = "Vimaleswaran, {Karani S} and Alana Cavadino and Berry, {Diane J} and Rolf Jorde and Dieffenbach, {Aida Karina} and Chen Lu and Alves, {Alexessander Couto} and Heerspink, {Hiddo J Lambers} and Emmi Tikkanen and Joel Eriksson and Andrew Wong and Massimo Mangino and Jablonski, {Kathleen A} and Nolte, {Ilja M} and Houston, {Denise K} and Ahluwalia, {Tarun Veer Singh} and {van der Most}, {Peter J} and Dorota Pasko and Lina Zgaga and Elisabeth Thiering and Veronique Vitart and Fraser, {Ross M} and Huffman, {Jennifer E} and {de Boer}, {Rudolf A} and Ben Sch{\"o}ttker and Kai-Uwe Saum and McCarthy, {Mark I} and Jos{\'e}e Dupuis and Karl-Heinz Herzig and Sylvain Sebert and Anneli Pouta and Jaana Laitinen and Kleber, {Marcus E} and Gerjan Navis and Mattias Lorentzon and Karen Jameson and Nigel Arden and Cooper, {Jackie A} and Jayshree Acharya and Rebecca Hardy and Olli Raitakari and Samuli Ripatti and Billings, {Liana K} and Jari Lahti and Clive Osmond and Penninx, {Brenda W} and Lars Rejnmark and Lohman, {Kurt K} and Lavinia Paternoster and S{\o}rensen, {Thorkild I A} and {LifeLines Cohort Study investigators}",

year = "2014",

month = sep,

day = "1",

doi = "10.1016/S2213-8587(14)70113-5",

language = "English",

volume = "2",

pages = "719--729",

journal = "The Lancet Diabetes & Endocrinology",

issn = "2213-8587",

publisher = "The Lancet Publishing Group",

number = "9",

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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, Tarun Veer 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 - Sørensen, Thorkild I A

AU - LifeLines Cohort Study investigators

PY - 2014/9/1

Y1 - 2014/9/1

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.

U2 - 10.1016/S2213-8587(14)70113-5

DO - 10.1016/S2213-8587(14)70113-5

M3 - Journal article

C2 - 24974252

SN - 2213-8587

VL - 2

SP - 719

EP - 729

JO - Wine Economics and Policy

JF - Wine Economics and Policy

IS - 9

ER -

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

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