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.
For some 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-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.
Patchen et al., 2/1/2021, retrospective, United Kingdom, Europe, peer-reviewed, 5 authors.
risk of COVID-19 severe case, 2.0% lower, RR 0.98, p = 0.11, 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, odds ratio converted to relative risk, >50nmol/L, baseline risk approximated with overall risk.
risk of COVID-19 case, no change, RR 1.00, p = 1.00, odds ratio converted to relative risk, >50nmol/L, 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.