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0 0.5 1 1.5 2+ Severe case 2% Improvement Relative Risk Hospitalization 0% Case 0% Patchen et al. Vitamin D for COVID-19 Sufficiency Favors vitamin D Favors control
Patchen, vitamin D sufficiency study: 2% lower severe cases [p=0.11], no change in hospitalization [p=1], and no change in cases [p=1]
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Genetically predicted serum vitamin D and COVID-19: a Mendelian randomization study
Patchen et al., BMJ Nutrition, Prevention & Health, doi:10.1136/bmjnph-2021-000255
1 Feb 2021    Source   PDF   Share   Tweet
UK Biobank Mendelian randomization study not finding significant differences in COVID-19 risk. The number of people predicted to have vitamin D deficiency does not appear to be provided.
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 [].
For reasons why Mendelian randomization may fail in this case, see []. 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.
risk of severe case, 2.0% lower, RR 0.98, p = 0.11, inverted to make RR<1 favor high D levels, odds ratio converted to relative risk, >50nmol/L, baseline risk approximated with overall risk.
risk of hospitalization, no change, RR 1.00, p = 1.00, inverted to make RR<1 favor high D levels, odds ratio converted to relative risk, >50nmol/L, baseline risk approximated with overall risk.
risk of case, no change, RR 1.00, p = 1.00, inverted to make RR<1 favor high D levels, odds ratio converted to relative risk, >50nmol/L, baseline risk approximated with overall risk.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Patchen et al., 1 Feb 2021, retrospective, United Kingdom, peer-reviewed, 5 authors.
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