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

Simple item page
dc.contributor.authorAspelund, Thor
dc.contributor.authorGrübler, Martin R.
dc.contributor.authorSmith, Albert V.
dc.contributor.authorGudmundsson, Elias F.
dc.contributor.authorKeppel, Martin
dc.contributor.authorCotch, Mary F.
dc.contributor.authorHarris, Tamara B.
dc.contributor.authorJorde, Rolf
dc.contributor.authorGrimnes, Guri
dc.contributor.authorJoakimsen, Ragnar
dc.contributor.authorSchirmer, Henrik
dc.contributor.authorWilsgaard, Tom
dc.contributor.authorMathiesen, Ellisiv B.
dc.contributor.authorNjølstad, Inger
dc.contributor.authorLøchen, Maja-Lisa
dc.contributor.authorMärz, Winfried
dc.contributor.authorKleber, Marcus E.
dc.contributor.authorTomaschitz, Andreas
dc.contributor.authorGrove-Laugesen, Diana
dc.contributor.authorRejnmark, Lars
dc.contributor.authorSwart, Karin M. A.
dc.contributor.authorBrouwer, Ingeborg A.
dc.contributor.authorLips, Paul
dc.contributor.authorVan Schoor, Natasja M.
dc.contributor.authorSempos, Christopher T.
dc.contributor.authorDurazo-Arvizu, Ramón A.
dc.contributor.authorŠkrabáková, Zuzana
dc.contributor.authorDowling, Kirsten G.
dc.contributor.authorCashman, Kevin D.
dc.contributor.authorKiely, Mairead E.
dc.contributor.authorPilz, Stefan
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorEiriksdottir, Gudny
dc.contributor.funderNational Institute for Health Researchen
dc.contributor.funderDivision of Intramural Research, National Institute of Allergy and Infectious Diseasesen
dc.contributor.funderIcelandic Heart Associationen
dc.contributor.funderIcelandic Parliamenten
dc.contributor.funderNational Institute on Deafness and Other Communication Disordersen
dc.contributor.funderNational Eye Instituteen
dc.date.accessioned2019-05-15T05:46:38Z
dc.date.available2019-05-15T05:46:38Z
dc.date.issued2019
dc.description.abstractThe 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 precisionen
dc.description.sponsorshipNational Institute on Deafness and Other Communication Disorders (NIDCD) Division of Scientific Programs (IAA Y2-DC_1004-02)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid74en
dc.identifier.citationAspelund, 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/nu11010074en
dc.identifier.doi10.3390/nu11010074en
dc.identifier.endpage12en
dc.identifier.issn2072-6643
dc.identifier.issued1en
dc.identifier.journaltitleNutrientsen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/7908
dc.identifier.volume11en
dc.language.isoenen
dc.publisherMDPI AGen
dc.relation.projectinfo: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.projectinfo:eu-repo/grantAgreement/NIH/NATIONAL EYE INSTITUTE/1ZIAEY000401-10/US/Age, Gene/environment Susceptibility Study In Iceland - Ocular Component/en
dc.relation.urihttps://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) licenseen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectVitamin Den
dc.subjectStandardized 25(OH)Den
dc.subjectMendelian randomizationen
dc.subjectMortalityen
dc.subjectCohortsen
dc.subjectIndividual participation dataen
dc.titleEffect of genetically low 25-hydroxyvitamin D on mortality risk: Mendelian randomization analysis in 3 large European cohortsen
dc.typeArticle (peer-reviewed)en
Files
Original bundle
Now showing 1 - 2 of 2
Thumbnail Image
Name:
nutrients-11-00074-v2.pdf
Size:
580.23 KB
Format:
Adobe Portable Document Format
Description:
Published version
Download
Thumbnail Image
Name:
nutrients-11-00074-s001.zip
Size:
87.88 KB
Format:
http://www.iana.org/assignments/media-types/application/zip
Description:
Supplementary files
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Medicine - Journal Articles
Food and Nutritional Sciences - Journal Articles
INFANT Research Centre - Journal Articles