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

Area of Science:

• Genetics
• Epidemiology
• Dermatology

Background:

• Observational studies suggest a link between vitamin D levels and psoriasis.
• However, these studies are limited by confounding and reverse causation.
• Causal inference is challenging with observational data.

Purpose of the Study:

• To investigate the causal relationship between vitamin D and psoriasis using Mendelian randomization (MR).
• To leverage genetic variants as instrumental variables for vitamin D levels.
• To provide robust evidence beyond observational associations.

Main Methods:

• Utilized genome-wide association study (GWAS) data from large European cohorts for discovery and replication.
• Employed genetic variants strongly associated with 25-hydroxyvitamin D (25OHD) as instrumental variables.
• Applied inverse-variance weighted (IVW) MR and robust sensitivity analyses to assess the association with psoriasis.

Main Results:

• Mendelian randomization analyses in both discovery and replication datasets showed no significant effect of 25-hydroxyvitamin D (25OHD) on psoriasis.
• Biologically validated and polygenic genetic instruments consistently indicated no impact of vitamin D on psoriasis risk.
• Statistical significance was not reached in any of the primary or sensitivity analyses.

Conclusions:

• The MR study does not support a causal association between vitamin D levels (25OHD) and psoriasis.
• These findings suggest that vitamin D may not play a direct causal role in the development of psoriasis.
• Conclusions are based on European ancestry data and may not generalize to other ethnicities.