Relationship between genetically proxied vitamin D and psoriasis risk: a Mendelian randomization study.

BACKGROUND: Observational research suggests that vitamin D levels affect psoriasis. However, observational studies are prone to potential confounding or reverse causation, which complicates interpreting the data and drawing causal conclusions.Objectives: We applied Mendelian randomization (MR) methods to comprehensively assess a potential association between vitamin D and psoriasis.

METHODS: Genetic variants strongly associated with 25-hydroxyvitamin D (25OHD) in a genome-wide association study (GWAS) of 417,580 individuals of European ancestry served as instrumental variables. As outcome variable, we used GWAS data of psoriasis (13,229 cases, 21,543 controls). We used (i) biologically validated genetic instruments and (ii) polygenic genetic instruments to assess the relation of genetically proxied vitamin D to psoriasis. We carried out inverse variance weighted (IVW) MR analyses for the primary analysis. In sensitivity analyses, we used robust MR approaches.

RESULTS: MR analyses did not show an effect of 25OHD on psoriasis. Neither the IVW MR analysis of the biologically validated instruments (OR = 0.99; 95%-CI = 0.88-1.12; p = 0.873) nor that of the polygenic genetic instruments (OR = 1.00; 95%-CI = 0.81-1.22; p = 0.973) revealed an impact of 25OHD on psoriasis.

CONCLUSIONS: The present MR study did not support the hypothesis that vitamin D levels measured by 25OHD affect psoriasis. This study was conducted on Europeans, so the conclusions may not be applicable to all ethnicities.