RGD Reference Report - Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. - Rat Genome Database

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

Authors: Vimaleswaran, Karani S  Cavadino, Alana  Berry, Diane J  LifeLines Cohort Study investigators,   Jorde, Rolf  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  Vitart, Veronique  Fraser, Ross M  Huffman, Jennifer E  de Boer, Rudolf A  Schöttker, Ben  Saum, Kai-Uwe  McCarthy, Mark I  Dupuis, Josée  Herzig, Karl-Heinz  Sebert, Sylvain  Pouta, Anneli  Laitinen, Jaana  Kleber, Marcus E  Navis, Gerjan  Lorentzon, Mattias  Jameson, Karen  Arden, Nigel  Cooper, Jackie A  Acharya, Jayshree  Hardy, Rebecca  Raitakari, Olli  Ripatti, Samuli  Billings, Liana K  Lahti, Jari  Osmond, Clive  Penninx, Brenda W  Rejnmark, Lars  Lohman, Kurt K  Paternoster, Lavinia  Stolk, Ronald P  Hernandez, Dena G  Byberg, Liisa  Hagström, Emil  Melhus, Håkan  Ingelsson, Erik  Mellström, Dan  Ljunggren, Osten  Tzoulaki, Ioanna  McLachlan, Stela  Theodoratou, Evropi  Tiesler, Carla M T  Jula, Antti  Navarro, Pau  Wright, Alan F  Polasek, Ozren  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,   Wilson, James F  Rudan, Igor  Salomaa, Veikko  Heinrich, Joachim  Campbell, Harry  Price, Jacqueline F  Karlsson, Magnus  Lind, Lars  Michaëlsson, Karl  Bandinelli, Stefania  Frayling, Timothy M  Hartman, Catharina A  Sørensen, Thorkild I A  Kritchevsky, Stephen B  Langdahl, Bente Lomholt  Eriksson, Johan G  Florez, Jose C  Spector, Tim D  Lehtimäki, Terho  Kuh, Diana  Humphries, Steve E  Cooper, Cyrus  Ohlsson, Claes  März, Winfried  de Borst, Martin H  Kumari, Meena  Kivimaki, Mika  Wang, Thomas J  Power, Chris  Brenner, Hermann  Grimnes, Guri  van der Harst, Pim  Snieder, Harold  Hingorani, Aroon D  Pilz, Stefan  Whittaker, John C  Järvelin, Marjo-Riitta  Hyppönen, Elina 
Citation: Vimaleswaran KS, etal., Lancet Diabetes Endocrinol. 2014 Sep;2(9):719-29. doi: 10.1016/S2213-8587(14)70113-5. Epub 2014 Jun 25.
RGD ID: 401901148
Pubmed: PMID:24974252   (View Abstract at PubMed)
PMCID: PMC4582411   (View Article at PubMed Central)
DOI: DOI:10.1016/S2213-8587(14)70113-5   (Journal Full-text)


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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  IAGP 401901148DNA:SNP:CDS:rs12794714 (human)RGD 
hypertension  ISOCYP2R1 (Homo sapiens)401901148; 401901148DNA:SNP:CDS:rs12794714 (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp2r1  (cytochrome P450, family 2, subfamily r, polypeptide 1)

Genes (Mus musculus)
Cyp2r1  (cytochrome P450, family 2, subfamily r, polypeptide 1)

Genes (Homo sapiens)
CYP2R1  (cytochrome P450 family 2 subfamily R member 1)


Additional Information