Vimaleswaran, Karani S and Cavadino, Alana and Berry, Diane J and Jorde, Rolf and Dieffenbach, Aida Karina and Lu, Chen and Alves, Alexessander Couto and Heerspink, Hiddo J Lambers and Tikkanen, Emmi and Eriksson, Joel and Wong, Andrew and Mangino, Massimo and Jablonski, Kathleen A and Nolte, Ilja M and Houston, Denise K and Ahluwalia, Tarunveer Singh and van der Most, Peter J and Pasko, Dorota and Zgaga, Lina and Thiering, Elisabeth and Vitart, Veronique and Fraser, Ross M and Huffman, Jennifer E and de Boer, Rudolf A and Schöttker, Ben and Saum, Kai-Uwe and McCarthy, Mark I and Dupuis, Josée and Herzig, Karl-Heinz and Sebert, Sylvain and Pouta, Anneli and Laitinen, Jaana and Kleber, Marcus E and Navis, Gerjan and Lorentzon, Mattias and Jameson, Karen and Arden, Nigel and Cooper, Jackie A and Acharya, Jayshree and Hardy, Rebecca and Raitakari, Olli and Ripatti, Samuli and Billings, Liana K and Lahti, Jari and Osmond, Clive and Penninx, Brenda W and Rejnmark, Lars and Lohman, Kurt K and Paternoster, Lavinia and Stolk, Ronald P and Hernandez, Dena G and Byberg, Liisa and Hagström, Emil and Melhus, Håkan and Ingelsson, Erik and Mellström, Dan and Ljunggren, Östen and Tzoulaki, Ioanna and McLachlan, Stela and Theodoratou, Evropi and Tiesler, Carla MT and Jula, Antti and Navarro, Pau and Wright, Alan F and Polasek, Ozren and Wilson, James F and Rudan, Igor and Salomaa, Veikko and Heinrich, Joachim and Campbell, Harry and Price, Jacqueline F and Karlsson, Magnus and Lind, Lars and Michaëlsson, Karl and Bandinelli, Stefania and Frayling, Timothy M and Hartman, Catharina A and Sørensen, Thorkild IA and Kritchevsky, Stephen B and Langdahl, Bente Lomholt and Eriksson, Johan G and Florez, Jose C and Spector, Tim D and Lehtimäki, Terho and Kuh, Diana and Humphries, Steve E and Cooper, Cyrus and Ohlsson, Claes and März, Winfried and de Borst, Martin H and Kumari, Meena and Kivimaki, Mika and Wang, Thomas J and Power, Chris and Brenner, Hermann and Grimnes, Guri and van der Harst, Pim and Snieder, Harold and Hingorani, Aroon D and Pilz, Stefan and Whittaker, John C and Järvelin, Marjo-Riitta and Hyppönen, Elina (2014) Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. The Lancet Diabetes & Endocrinology, 2 (9). pp. 719-729. DOI https://doi.org/10.1016/s2213-8587(14)70113-5
Vimaleswaran, Karani S and Cavadino, Alana and Berry, Diane J and Jorde, Rolf and Dieffenbach, Aida Karina and Lu, Chen and Alves, Alexessander Couto and Heerspink, Hiddo J Lambers and Tikkanen, Emmi and Eriksson, Joel and Wong, Andrew and Mangino, Massimo and Jablonski, Kathleen A and Nolte, Ilja M and Houston, Denise K and Ahluwalia, Tarunveer Singh and van der Most, Peter J and Pasko, Dorota and Zgaga, Lina and Thiering, Elisabeth and Vitart, Veronique and Fraser, Ross M and Huffman, Jennifer E and de Boer, Rudolf A and Schöttker, Ben and Saum, Kai-Uwe and McCarthy, Mark I and Dupuis, Josée and Herzig, Karl-Heinz and Sebert, Sylvain and Pouta, Anneli and Laitinen, Jaana and Kleber, Marcus E and Navis, Gerjan and Lorentzon, Mattias and Jameson, Karen and Arden, Nigel and Cooper, Jackie A and Acharya, Jayshree and Hardy, Rebecca and Raitakari, Olli and Ripatti, Samuli and Billings, Liana K and Lahti, Jari and Osmond, Clive and Penninx, Brenda W and Rejnmark, Lars and Lohman, Kurt K and Paternoster, Lavinia and Stolk, Ronald P and Hernandez, Dena G and Byberg, Liisa and Hagström, Emil and Melhus, Håkan and Ingelsson, Erik and Mellström, Dan and Ljunggren, Östen and Tzoulaki, Ioanna and McLachlan, Stela and Theodoratou, Evropi and Tiesler, Carla MT and Jula, Antti and Navarro, Pau and Wright, Alan F and Polasek, Ozren and Wilson, James F and Rudan, Igor and Salomaa, Veikko and Heinrich, Joachim and Campbell, Harry and Price, Jacqueline F and Karlsson, Magnus and Lind, Lars and Michaëlsson, Karl and Bandinelli, Stefania and Frayling, Timothy M and Hartman, Catharina A and Sørensen, Thorkild IA and Kritchevsky, Stephen B and Langdahl, Bente Lomholt and Eriksson, Johan G and Florez, Jose C and Spector, Tim D and Lehtimäki, Terho and Kuh, Diana and Humphries, Steve E and Cooper, Cyrus and Ohlsson, Claes and März, Winfried and de Borst, Martin H and Kumari, Meena and Kivimaki, Mika and Wang, Thomas J and Power, Chris and Brenner, Hermann and Grimnes, Guri and van der Harst, Pim and Snieder, Harold and Hingorani, Aroon D and Pilz, Stefan and Whittaker, John C and Järvelin, Marjo-Riitta and Hyppönen, Elina (2014) Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. The Lancet Diabetes & Endocrinology, 2 (9). pp. 719-729. DOI https://doi.org/10.1016/s2213-8587(14)70113-5
Vimaleswaran, Karani S and Cavadino, Alana and Berry, Diane J and Jorde, Rolf and Dieffenbach, Aida Karina and Lu, Chen and Alves, Alexessander Couto and Heerspink, Hiddo J Lambers and Tikkanen, Emmi and Eriksson, Joel and Wong, Andrew and Mangino, Massimo and Jablonski, Kathleen A and Nolte, Ilja M and Houston, Denise K and Ahluwalia, Tarunveer Singh and van der Most, Peter J and Pasko, Dorota and Zgaga, Lina and Thiering, Elisabeth and Vitart, Veronique and Fraser, Ross M and Huffman, Jennifer E and de Boer, Rudolf A and Schöttker, Ben and Saum, Kai-Uwe and McCarthy, Mark I and Dupuis, Josée and Herzig, Karl-Heinz and Sebert, Sylvain and Pouta, Anneli and Laitinen, Jaana and Kleber, Marcus E and Navis, Gerjan and Lorentzon, Mattias and Jameson, Karen and Arden, Nigel and Cooper, Jackie A and Acharya, Jayshree and Hardy, Rebecca and Raitakari, Olli and Ripatti, Samuli and Billings, Liana K and Lahti, Jari and Osmond, Clive and Penninx, Brenda W and Rejnmark, Lars and Lohman, Kurt K and Paternoster, Lavinia and Stolk, Ronald P and Hernandez, Dena G and Byberg, Liisa and Hagström, Emil and Melhus, Håkan and Ingelsson, Erik and Mellström, Dan and Ljunggren, Östen and Tzoulaki, Ioanna and McLachlan, Stela and Theodoratou, Evropi and Tiesler, Carla MT and Jula, Antti and Navarro, Pau and Wright, Alan F and Polasek, Ozren and Wilson, James F and Rudan, Igor and Salomaa, Veikko and Heinrich, Joachim and Campbell, Harry and Price, Jacqueline F and Karlsson, Magnus and Lind, Lars and Michaëlsson, Karl and Bandinelli, Stefania and Frayling, Timothy M and Hartman, Catharina A and Sørensen, Thorkild IA and Kritchevsky, Stephen B and Langdahl, Bente Lomholt and Eriksson, Johan G and Florez, Jose C and Spector, Tim D and Lehtimäki, Terho and Kuh, Diana and Humphries, Steve E and Cooper, Cyrus and Ohlsson, Claes and März, Winfried and de Borst, Martin H and Kumari, Meena and Kivimaki, Mika and Wang, Thomas J and Power, Chris and Brenner, Hermann and Grimnes, Guri and van der Harst, Pim and Snieder, Harold and Hingorani, Aroon D and Pilz, Stefan and Whittaker, John C and Järvelin, Marjo-Riitta and Hyppönen, Elina (2014) Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. The Lancet Diabetes & Endocrinology, 2 (9). pp. 719-729. DOI https://doi.org/10.1016/s2213-8587(14)70113-5
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LifeLines Cohort Study investigators; International Consortium for Blood Pressure (ICBP); Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium; Global Blood Pressure Genetics (Global BPGen) consortium; Caroline Hayward; Humans; Hypertension; Vitamin D Deficiency; Genetic Predisposition to Disease; Oxidoreductases Acting on CH-CH Group Donors; Vitamin D; Body Mass Index; Phenotype; Polymorphism, Single Nucleotide; Adult; Middle Aged; Female; Male; Randomized Controlled Trials as Topic; Mendelian Randomization Analysis; Cholestanetriol 26-Monooxygenase; Cytochrome P450 Family 2 |
| Subjects: | H Social Sciences > HA Statistics R Medicine > R Medicine (General) |
| Divisions: | Faculty of Social Sciences Faculty of Social Sciences > Institute for Social and Economic Research |
| SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
| Depositing User: | Unnamed user with email elements@essex.ac.uk |
| Date Deposited: | 06 Feb 2015 14:13 |
| Last Modified: | 04 Dec 2024 06:58 |
| URI: | http://repository.essex.ac.uk/id/eprint/12672 |
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