Live longer if have more than 40 ng of Vitamin D (gene analysis of 10,500 people) – Jan 2019

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

Nutrients 2019, 11(1), 74; https://doi.org/10.3390/nu11010074

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Figure 1. Mortality rate (log-scale) for 10 years from all causes by level of standardized 25-hydroxyvitamin D.
A rug and density plot are superimposed to demonstrate where most of the 25(OH)D measurements lie.
Fitted associations are shown as linear (green line), log-linear (black line), and spline (broken line)

Table 3

Authors Thor Aspelund 1,2, Martin R. Grübler 3,4,5, Albert V. Smith 1,2, Elias F. Gudmundsson 1, Martin Keppel 6, Mary Frances Cotch 7, Tamara B. Harris 8, Rolf Jorde 9, Guri Grimnes 9, Ragnar Joakimsen 9, Henrik Schirmer 10, Tom Wilsgaard 11, Ellisiv B. Mathiesen 12,13, Inger Njølstad 11, Maja-Lisa Løchen 11, Winfried März 14,15,16, Marcus E. Kleber 14,17, Andreas Tomaschitz 4,18,19, Diana Grove-Laugesen 20, Lars Rejnmark 20, Karin M. A. Swart 21, Ingeborg A. Brouwer 22, Paul Lips 23, Natasja M. van Schoor 21, Christopher T. Sempos 24, Ramón A. Durazo-Arvizu 25, Zuzana Škrabáková 26, Kirsten G. Dowling 26, Kevin D. Cashman 26,27, Mairead Kiely 26,28, Stefan Pilz 3,21, Vilmundur Gudnason 1,2 and Gudny Eiriksdottir 1,*
(This article belongs to the Special Issue Nutrition Intake and Skin Health: Vitamin D and beyond) 7 papers as of Nov 2019

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

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Conclusions

In conclusion, the results of this MR study may argue in favor of a causal relationship between vitamin D deficiency and increased all-cause mortality in a combined sample from three European cohort studies. These data support a previous Danish MR study with similar effects size. It is also in line with the dose-response seen in observational epidemiological studies as well as meta-analyses of vitamin D RCTs, which suggest that low 25(OH)D levels may be detrimental for survival. These findings on vitamin D and mortality deserve consideration in the public health discussion regarding the value, design, and implementation of innovative approaches to improve the vitamin D status of the general population.

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