Bidirectional Mendelian Randomization Study Identifies No Genetic Link Between Psoriasis and Diabetes

Area of Science:

• Genetics
• Epidemiology
• Metabolic Diseases

Background:

• Psoriasis (Ps) and diabetes mellitus (DM) have a proposed bidirectional link, but the causal relationship is unclear.
• Existing epidemiological studies suggest an association, necessitating genetic investigation.

Purpose of the Study:

• To investigate the potential causal relationship between psoriasis and Type 1 (T1DM) and Type 2 diabetes mellitus (T2DM) using bidirectional Mendelian randomization.
• To analyze genetic data from European ancestry individuals to determine if genetic variants for psoriasis influence DM risk, and vice versa.

Main Methods:

• Utilized summary statistics from genome-wide association studies (GWAS) of psoriasis, T1DM, and T2DM from UK Biobank and FinnGen datasets.
• Employed inverse-variance weighted (IVW) as the primary Mendelian randomization (MR) method, with sensitivity analyses including MR-Egger, weighted median, and Cochran's Q test for pleiotropy.
• Conducted bidirectional MR analyses to assess causality in both directions: Ps to DM and DM to Ps.

Main Results:

• No significant causal associations were found between DM and Ps, nor between Ps and T1DM.
• While some positive correlations between Ps and T2DM were observed, the aggregate evidence did not establish a causal link.
• Sensitivity analyses confirmed no evidence of horizontal pleiotropy and validated the robustness of the findings.

Conclusions:

• This genetic study provides no evidence for a causal effect of psoriasis on diabetes mellitus (T1DM or T2DM) or vice versa in individuals of European ancestry.
• Further research in diverse populations is recommended to explore potential associations between psoriasis and diabetes mellitus.
• The findings contribute to understanding the complex interplay between autoimmune and metabolic diseases.