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0 0.5 1 1.5 2+ COVID-19 severity -32% Improvement Relative Risk Case -8% c19early.org/d Amin et al. Vitamin D for COVID-19 Sufficiency Favors vitamin D Favors control
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
Amin et al., BMJ Nutrition, Prevention & Health, doi:10.1136/bmjnph-2020-000151
7 Jan 2021    Source   PDF   Share   Tweet
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.
Mendelian randomization studies compare the estimated effect of SNPs associated with variation in vitamin D levels on the health outcomes in large numbers of patients. For more background on Mendelian randomization studies and their limitations see [nature.com].
For reasons why Mendelian randomization may fail in this case, see [nutrition.bmj.com]. Authors suggest that it may come down to the use of 25(OH)D 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(OH)D 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(OH)D 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.
[Grant] suggest that the primary reasons for Mendelien randomization failure include that the total SNP-induced variation in 25(OH)D has often been less than assay variance, and that genome-wide association studies of SNP effects have been made on the full range of 25(OH)D levels, while the data is non-linear with a significant percentage in the low and high plateaus of the outcome relationships.
COVID-19 severity, 32.3% higher, RR 1.32, p = 0.20, high D levels 140,898, low D levels 35,079, inverted to make RR<1 favor high D levels, odds ratio converted to relative risk, >=50nmol/L vs. <25nmol/L, MR Egger, baseline risk approximated with overall risk.
risk of case, 7.6% higher, RR 1.08, p = 0.14, high D levels 140,898, low D levels 35,079, inverted to make RR<1 favor high D levels, 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. Submit updates
Amin et al., 7 Jan 2021, retrospective, population-based cohort, United Kingdom, peer-reviewed, 2 authors.
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