Causal analysis shows evidence of atopic dermatitis leading to an increase in vitamin D levels

Abstract

Atopic dermatitis (AD) patients have been observed to have lower vitamin D levels. Previous studies have found little evidence that vitamin D levels causally influence the risk of AD, but the reverse direction has not yet been investigated. Here we used Mendelian Randomization to assess the causal relationship between AD and serum vitamin D levels, using genetic data from the most recent GWA studies of vitamin D and AD. There was little evidence for vitamin D levels causally influencing AD risk (odds per standard deviations increase in log-transformed vitamin D levels =1.233, 95% CI 0.927 to 1.639, P-value =0.150). However, genetic liability for AD raises serum vitamin D levels by 0.043 (95% CI 0.017 to 0.069) standard deviations per doubling of odds of disease (P-value =0.001). The AD-associated filaggrin (FLG) mutation R501X appears to show a particularly strong relationship with vitamin D. However, the relationship between AD and vitamin D holds when R501X is omitted (0.018, 95% CI 0.004 to 0.031, P-value =0.008). We found evidence that AD is causally associated with an increase in serum vitamin D levels. Whilst the AD-associated FLG gene has a particularly strong relationship with vitamin D, other AD SNPs show a consistent direction of effect, suggesting that AD more generally influences serum vitamin D levels.