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) |