Next Article in Journal
Stabilization of Vitamin D in Pea Protein Isolate Nanoemulsions Increases Its Bioefficacy in Rats
Next Article in Special Issue
Dietary Patterns Associated with Sebum Content, Skin Hydration and pH, and Their Sex-Dependent Differences in Healthy Korean Adults
Previous Article in Journal
Elemental Metabolomics and Pregnancy Outcomes
Previous Article in Special Issue
Tectorigenin, a Flavonoid-Based Compound of Leopard Lily Rhizome, Attenuates UV-B-Induced Apoptosis and Collagen Degradation by Inhibiting Oxidative Stress in Human Keratinocytes
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessArticle

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

1
Icelandic Heart Association, 201 Kopavogur, Iceland
2
Faculty of Medicine, School of Health Sciences, University of Iceland, 101 Reykjavik, Iceland
3
Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, 8036 Graz, Austria
4
Department of Cardiology, Medical University of Graz, 8036 Graz, Austria
5
Swiss Cardiovascular Center Bern, Department of Cardiology, Bern University Hospital, University of Bern, 3012 Bern, Switzerland
6
Department of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, Austria
7
Division of Epidemiology and Clinical Applications, National Eye Institute, Bethesda, MD 20892-1204, USA
8
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD 20814, USA
9
Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, 9037 Tromsø, Norway
10
Tromsø Cardiovascular Research Group UNN, Department of Clinical Medicine, UiT The Arctic University of Norway, 9037 Tromsø, Norway
11
Department of Community Medicine, UiT The Arctic University of Norway, 9037 Tromsø, Norway
12
Brain and Circulation Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, 9037 Tromsø, Norway
13
Department of Neurology, University Hospital of North Norway, 9038 Tromsø, Norway
14
Medical Clinic V, Mannheim Medical Faculty, University of Heidelberg, 68167 Mannheim, Germany
15
SYNLAB Academy, SYNLAB Holding Deutschland GmbH, P5, 7, D-68161 Mannheim or Gubener Straße 39, 86156 Augsburg, Germany
16
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria
17
NutriCard—Competence Cluster for Nutrition and Cardiovascular Health, Institute for Nutritional Science, Friedrich-Schiller-University, 07743 Jena, Germany
18
Specialist Clinic for Rehabilitation Bad Aussee, 8990 Bad Aussee, Austria
19
Department of Internal Medicine—Cardiology, Charité University Hospital Berlin, Campus Virchow Klinikum, 10117 Berlin, Germany
20
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark
21
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Epidemiology and Biostatistics, Amsterdam Public Health, 1081 Amsterdam, The Netherlands
22
Department of Health Sciences, Faculty of Sciences and Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, 1081 Amsterdam, The Netherlands
23
Department of Internal Medicine, Endocrine Section, VU University Medical Center, 1081 Amsterdam, The Netherlands
24
Office of Dietary Supplements, National Institute of Health, Bethesda, MD 20892-7517, USA
25
Department of Public Health Sciences, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA
26
Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, Cork T12K8AF, Ireland
27
Department of Medicine, University College Cork, Cork T12K8AF, Ireland
28
Irish Centre for Fetal and Neonatal Translational Research [INFANT], University College Cork, Cork T12K8AF, Ireland
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(1), 74; https://doi.org/10.3390/nu11010074
Received: 21 November 2018 / Revised: 13 December 2018 / Accepted: 24 December 2018 / Published: 2 January 2019
(This article belongs to the Special Issue Nutrition Intake and Skin Health: Vitamin D and beyond)
  |  
PDF [580 KB, uploaded 3 January 2019]
  |  

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. View Full-Text
Keywords: Vitamin D; standardized 25(OH)D; Mendelian randomization; mortality; cohorts; Individual Participant Data Vitamin D; standardized 25(OH)D; Mendelian randomization; mortality; cohorts; Individual Participant Data
Figures

Figure 1

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 (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Nutrients EISSN 2072-6643 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top