Effect of genetically low 25-hydroxyvitamin D on mortality risk: Mendelian randomization analysis in 3 large European cohorts

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dc.contributor.author Aspelund, Thor
dc.contributor.author Grübler, Martin R.
dc.contributor.author Smith, Albert V.
dc.contributor.author Gudmundsson, Elias F.
dc.contributor.author Keppel, Martin
dc.contributor.author Cotch, Mary F.
dc.contributor.author Harris, Tamara B.
dc.contributor.author Jorde, Rolf
dc.contributor.author Grimnes, Guri
dc.contributor.author Joakimsen, Ragnar
dc.contributor.author Schirmer, Henrik
dc.contributor.author Wilsgaard, Tom
dc.contributor.author Mathiesen, Ellisiv B.
dc.contributor.author Njølstad, Inger
dc.contributor.author Løchen, Maja-Lisa
dc.contributor.author März, Winfried
dc.contributor.author Kleber, Marcus E.
dc.contributor.author Tomaschitz, Andreas
dc.contributor.author Grove-Laugesen, Diana
dc.contributor.author Rejnmark, Lars
dc.contributor.author Swart, Karin M. A.
dc.contributor.author Brouwer, Ingeborg A.
dc.contributor.author Lips, Paul
dc.contributor.author Van Schoor, Natasja M.
dc.contributor.author Sempos, Christopher T.
dc.contributor.author Durazo-Arvizu, Ramón A.
dc.contributor.author Škrabáková, Zuzana
dc.contributor.author Dowling, Kirsten G.
dc.contributor.author Cashman, Kevin D.
dc.contributor.author Kiely, Mairead E.
dc.contributor.author Pilz, Stefan
dc.contributor.author Gudnason, Vilmundur
dc.contributor.author Eiriksdottir, Gudny
dc.date.accessioned 2019-05-15T05:46:38Z
dc.date.available 2019-05-15T05:46:38Z
dc.date.issued 2019
dc.identifier.citation Aspelund, T., Grübler, M., Smith, A., Gudmundsson, E., Keppel, M., Cotch, M., Harris, T., Jorde, R., Grimnes, G., Joakimsen, R. and Schirmer, H., 2019. Effect of genetically low 25-hydroxyvitamin D on mortality risk: mendelian randomization analysis in 3 large European cohorts. Nutrients, 11(1), 74 (12pp). DOI: 10.3390/nu11010074 en
dc.identifier.volume 11 en
dc.identifier.issued 1 en
dc.identifier.startpage 1 en
dc.identifier.endpage 12 en
dc.identifier.issn 2072-6643
dc.identifier.uri http://hdl.handle.net/10468/7908
dc.identifier.doi 10.3390/nu11010074 en
dc.description.abstract The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes CYP2R1 (rs12794714, rs10741657) and DHCR7/NADSYN1 (rs12785878, rs11234027), were combined in two allelic scores. Cox proportional hazards regression models were used with the ratio estimator and the delta method for calculating the hazards ratio (HR) and standard error of genetically determined 25(OH)D effect on all-cause mortality. We included 10,501 participants (50.1% females, 67.1±10.1 years) of whom 4003 died during a median follow-up of 10.4 years. The observed adjusted HR for all-cause mortality per decrease in 25(OH)D by 20 nmol/L was 1.20 (95% CI: 1.15–1.25). The HR per 20 nmol/L decrease in genetically determined 25(OH)D was 1.32 (95% CI: 0.80–2.24) and 1.35 (95% CI of 0.81 to 2.37) based on the two scores. In conclusion, the results of this MR study in a combined sample from three European cohort studies provide further support for a causal relationship between vitamin D deficiency and increased all-cause mortality. However, as the current study, even with ~10,000 participants, was underpowered for the study of the effect of the allele score on mortality, larger studies on genetics and mortality are needed to improve the precision en
dc.description.sponsorship National Institute on Deafness and Other Communication Disorders (NIDCD) Division of Scientific Programs (IAA Y2-DC_1004-02) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher MDPI AG en
dc.relation.uri https://www.mdpi.com/2072-6643/11/1/74
dc.rights © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license en
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ en
dc.subject Vitamin D en
dc.subject Standardized 25(OH)D en
dc.subject Mendelian randomization en
dc.subject Mortality en
dc.subject Cohorts en
dc.subject Individual participation data en
dc.title Effect of genetically low 25-hydroxyvitamin D on mortality risk: Mendelian randomization analysis in 3 large European cohorts en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Kevin Cashman, School of Food and Nutritional Sciences, University College Cork, Cork, Ireland. +353-21-490-3000 Email: k.cashman@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder National Institute for Health Research en
dc.contributor.funder Division of Intramural Research, National Institute of Allergy and Infectious Diseases en
dc.contributor.funder Icelandic Heart Association en
dc.contributor.funder Icelandic Parliament en
dc.contributor.funder National Institute on Deafness and Other Communication Disorders en
dc.contributor.funder National Eye Institute en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Nutrients en
dc.internal.IRISemailaddress k.cashman@ucc.ie en
dc.identifier.articleid 74 en
dc.relation.project info:eu-repo/grantAgreement/NIH/NATIONAL INSTITUTE ON AGING/N01AG012100-019/US/AGES STUDY-THE REYKJAVIK STUDY OF HEALTHY AGING FOR THE NEW MILLENNIUM-26012100/ en
dc.relation.project info:eu-repo/grantAgreement/NIH/NATIONAL EYE INSTITUTE/1ZIAEY000401-10/US/Age, Gene/environment Susceptibility Study In Iceland - Ocular Component/ en


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© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license Except where otherwise noted, this item's license is described as © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license
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