Investigating Pleiotropy Between Depression and Autoimmune Diseases Using the UK Biobank

Epidemiological studies report increased comorbidity between depression and autoimmune diseases. The role of shared genetic influences in the observed comorbidity is unclear. We investigated the evidence for pleiotropy between these traits in the UK Biobank (UKB).

We defined autoimmune and depression cases using hospital episode statistics, self-reported conditions and medications, and mental health questionnaires. Pairwise comparisons of depression prevalence between autoimmune cases and controls, and vice versa, were performed. Cross-trait polygenic risk score (PRS) analyses tested for pleiotropy, i.e., whether PRSs for depression could predict autoimmune disease status, and vice versa.

We identified 28,479 cases of autoimmune diseases (pooling across 14 traits) and 324,074 autoimmune controls, and 65,075 cases of depression and 232,552 depression controls. The prevalence of depression was significantly higher in autoimmune cases than in controls, and similarly, the prevalence of autoimmune disease was higher in depression cases than in controls. PRSs for myasthenia gravis and psoriasis were significantly higher in depression cases than in controls (p < 5.2 × 10^-5, R ² ≤ 0.04%). PRSs for depression were significantly higher in inflammatory bowel disease, psoriasis, psoriatic arthritis, rheumatoid arthritis, and type 1 diabetes cases than in controls (p < 5.8 × 10^-5, R ² range = 0.06%-0.27%), and lower in celiac disease cases than in controls (p < 5.4 × 10^-7, R ² range = 0.11%-0.15%).

Consistent with the literature, depression was more common in individuals with autoimmune diseases than in controls, and vice versa. PRSs showed some evidence for involvement of shared genetic factors, but the modest R ² values suggest that shared genetic architecture accounts for a small proportion of the increased risk across traits.