Weak Evidence of Causal Relationship of Vitamin D and Atopic Dermatitis

A genetic analysis has found weak evidence that vitamin D causally influences atopic dermatitis, and vitamin D supplementation is not supported as a therapy for the disorder, according to study findings published in the Journal of Investigative Dermatology.

Researchers used genome-wide association study (GWAS) data from the most recent vitamin D meta-analysis to identify potential evidence of causality and the direction of causal effect of vitamin D level and atopic dermatitis risk. They derived a genetic instrument of 59 independent single nucleotide polymorphisms (SNPs) (r² < 0.001) reported to be most strongly associated with 25-OHD levels. Summary GWAS data were also obtained from a recent atopic dermatitis GWAS meta-analysis.

“There was little evidence that vitamin D levels causally influence atopic dermatitis risk (odds ratio per SD change in log-transformed 25-OHD levels = 1.233, 95% CI 0.927-1.639, P = .150),” according to the researchers.

The causal effect of atopic dermatitis genetic risk on vitamin D levels was also investigated with an atopic dermatitis instrument of 24 SNPs reported in the most current atopic dermatitis GWAS. Strong evidence was found of atopic dermatitis genetic risk causally increasing log-transformed 25-OHD concentrations by 0.043 SD per doubling odds of atopic dermatitis (95% CI 0.017-0.069, P = .001), according to the study authors.

A genetic risk score for atopic dermatitis was tested in the UK Biobank for a potential association with potential confounders. Regression analyses found weak associations between the atopic dermatitis genetic risk score and lower BMI and with educational attainment.

 “We have found evidence that atopic dermatitis is causally associated with an increase in serum vitamin D levels,” stated the researchers. “This is not consistent with observational reports of atopic dermatitis patients with lower vitamin D levels … and suggests that the true nature of the relationship may have been masked by confounders with opposing effects on vitamin D and atopic dermatitis such as obesity, socioeconomic status, pollution, and latitude.”

Although the atopic dermatitis–associated filaggrin (FLG) gene has a particularly strong relationship with vitamin D, other atopic dermatitis SNPs show a consistent direction of effect when omitting this locus, suggesting that atopic dermatitis more generally influences serum vitamin D levels, according to the study authors.

“There is weak evidence that vitamin D causally influences atopic dermatitis,” stated the investigators of their study. “Our findings suggest that vitamin D supplementation is not supported as an atopic dermatitis therapy.”

The researchers noted that further investigation is needed to determine the mechanisms of the causal effect of atopic dermatitis genetic risk on serum vitamin D levels.

“Stratifying future vitamin D and phototherapy trials and epidemiological analyses by FLG status may assist in evaluating the contribution of different mechanisms,” the study authors concluded.

Disclosures: One of the study authors reported an affiliation with the pharmaceutical industry. Please see the original reference for a full list of disclosures.

Reference

Drodge DR, Budu-Aggrey A, Paternoster L. Causal analysis shows evidence of atopic dermatitis leading to an increase in vitamin D levels [published online October 14, 2020]. J Investig Dermatol. doi: https://doi.org/10.1016/j.jid.2020.09.013