Show simple item record

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 Frances
dc.contributor.authorHarris, Tamara B.
dc.contributor.authorJorde, Rolf
dc.contributor.authorGrimnes, Guri
dc.contributor.authorJoakimsen, Ragnar Martin
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
dc.contributor.authorPilz, Stefan
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorEiríksdóttir, Gudny
dc.date.accessioned2019-10-14T13:37:22Z
dc.date.available2019-10-14T13:37:22Z
dc.date.issued2019-01-02
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 <i>CYP2R1</i> (rs12794714, rs10741657) and <i>DHCR7/NADSYN1</i> (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_US
dc.description.sponsorshipNational Institutes of Health NIA Intramural Research Program Hjartavernd (the Icelandic Heart Association) Althingi (the Icelandic Parliament) National Eye Institute National Institute on Deafness and Other Communication Disordersen_US
dc.descriptionSource at <a href=https://doi.org/10.3390/nu11010074>https://doi.org/10.3390/nu11010074</a>.en_US
dc.identifier.citationAspelund, T., Grübler, M.R., Smith, A.V., Gudmundsson, E.F., Keppel, M, Cotch, M.F., ... Eiríksdóttir, G. (2019). Effect of genetically low 25-hydroxyvitamin D on mortality risk: Mendelian randomization analysis in 3 large european cohorts. <i>Nutrients, 11</i>(1), 74. https://doi.org/10.3390/nu11010074en_US
dc.identifier.cristinIDFRIDAID 1693001
dc.identifier.doi10.3390/nu11010074
dc.identifier.issn2072-6643
dc.identifier.urihttps://hdl.handle.net/10037/16397
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.relation.journalNutrients
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Health sciences: 800::Epidemiology medical and dental statistics: 803en_US
dc.subjectVDP::Medisinske Fag: 700::Helsefag: 800::Epidemiologi medisinsk og odontologisk statistikk: 803en_US
dc.subjectVitamin Den_US
dc.subjectstandardized 25(OH)Den_US
dc.subjectMendelian randomizationen_US
dc.subjectmortalityen_US
dc.subjectcohortsen_US
dc.subjectIndividual Participant Dataen_US
dc.titleEffect of genetically low 25-hydroxyvitamin D on mortality risk: Mendelian randomization analysis in 3 large European cohortsen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


File(s) in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record