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Effect of Genetically Low 25-Hydroxyvitamin D on Mortality Risk: Mendelian Randomization Analysis in 3 Large European Cohorts

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dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.author Aspelund, Thor
dc.contributor.author Grübler, Martin R.
dc.contributor.author Smith, Albert Vernon
dc.contributor.author Gudmundsson, Elias Freyr
dc.contributor.author Keppel, Martin
dc.contributor.author Cotch, Mary Frances
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
dc.contributor.author Pilz, Stefan
dc.contributor.author Gudnason, Vilmundur
dc.contributor.author Eiriksdottir, Gudny
dc.date.accessioned 2020-10-14T13:52:09Z
dc.date.available 2020-10-14T13:52:09Z
dc.date.issued 2019-01-02
dc.identifier.citation Aspelund, T.; Grübler, M.R.; Smith, A.V.; Gudmundsson, E.F.; Keppel, M.; Cotch, M.F.; Harris, T.B.; Jorde, R.; Grimnes, G.; Joakimsen, R.; Schirmer, H.; Wilsgaard, T.; Mathiesen, E.B.; Njølstad, I.; Løchen, M.-L.; März, W.; Kleber, M.E.; Tomaschitz, A.; Grove-Laugesen, D.; Rejnmark, L.; Swart, K.M.A.; Brouwer, I.A.; Lips, P.; Van Schoor, N.M.; Sempos, C.T.; Durazo-Arvizu, R.A.; Škrabáková, Z.; Dowling, K.G.; Cashman, K.D.; Kiely, M.; Pilz, S.; Gudnason, V.; Eiriksdottir, G. Effect of Genetically Low 25-Hydroxyvitamin D on Mortality Risk: Mendelian Randomization Analysis in 3 Large European Cohorts. Nutrients 2019, 11, 74.
dc.identifier.issn 2072-6643
dc.identifier.uri https://hdl.handle.net/20.500.11815/2118
dc.description Publisher's version (útgefin grein)
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.
dc.description.sponsorship Age, Gene/Environment Susceptibility Reykjavik Study: This study has been funded by NIH contract N01-AG012100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament), an Intramural Research Program Award (ZIAEY000401) from the National Eye Institute, an award from the National Institute on Deafness and Other Communication Disorders (NIDCD) Division of Scientific Programs (IAA Y2-DC_1004-02), The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063. Ludwigshafen RIsk and Cardiovascular Health Study: None. Tromsø Study: None.
dc.format.extent 74
dc.language.iso en
dc.publisher MDPI AG
dc.relation.ispartofseries Nutrients;11(1)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Food Science
dc.subject Cohorts
dc.subject Individual participant data
dc.subject Mendelian randomization
dc.subject Mortality
dc.subject Standardized 25(OH)D
dc.subject Vitamin D
dc.subject Næringarfræði
dc.subject D vítamín
dc.subject Dánartíðni
dc.subject Tilviksrannsóknir
dc.subject Arfgengi
dc.title Effect of Genetically Low 25-Hydroxyvitamin D on Mortality Risk: Mendelian Randomization Analysis in 3 Large European Cohorts
dc.type info:eu-repo/semantics/article
dcterms.license This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
dc.description.version Peer Reviewed
dc.identifier.journal Nutrients
dc.identifier.doi 10.3390/nu11010074
dc.relation.url https://www.mdpi.com/2072-6643/11/1/74/pdf
dc.contributor.department Læknadeild (HÍ)
dc.contributor.department Faculty of Medicine (UI)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)

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