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Vitamin D study #59 of 96
1/7 Analysis of outcomes based on serum levels
Amin et al., BMJ Nutrition, Prevention & Health, doi:10.1136/bmjnph-2020-000151 (Peer Reviewed)
No evidence that vitamin D is able to prevent or affect the severity of COVID-19 in individuals with European ancestry: a Mendelian randomisation study of open data
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Analysis of vitamin D levels and COVID-19 cases and severity based on genetic predisposition to higher vitamin D levels or lower vitamin D deficiency, finding no significant association.
For some background on Mendelian randomization studies and their limitations see [1].
For reasons why Mendelian randomization may fail in this case, see [2]. Authors suggest that it may come down to the use of 25-OHD concentration in serum as a less than ideal proxy for vitamin D status of cells involved in the immune response. For most other purposes, it may not matter much that unbound (free) 25-OHD is the better predictor of vitamin D deficiency and the resulting unfavourable outcomes. But for the MR analysis, the genetic instrument is strongly dominated by variation in the GC gene which modulates the concentration of vitamin D-binding protein (VDBP) in blood and thereby indirectly the concentrations of 25-OHD and 1,25-dihydroxy vitamin D. Thus, the common GC alleles rs4588A and rs7041T are both associated with much lower than average vitamin D concentrations. In contrast, directly measured unbound (free) vitamin D concentrations are minimally affected by these alleles, if at all.

Amin et al., 1/7/2021, retrospective, United Kingdom, Europe, peer-reviewed, 2 authors.
COVID-19 severity, 32.3% higher, RR 1.32, p = 0.20, odds ratio converted to relative risk, >=50nmol/L vs. <25nmol/L, MR Egger, baseline risk approximated with overall risk.
risk of COVID-19 case, 7.6% higher, RR 1.08, p = 0.14, odds ratio converted to relative risk, >=50nmol/L vs. <25nmol/L, MR Egger, baseline risk approximated with overall risk.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. For an individual study the most serious outcome may have a smaller number of events and lower statistical signficance, however this provides the strongest evidence for the most serious outcomes when combining the results of many trials.
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