Investigating pleiotropy between depression and autoimmune diseases using the UK Biobank

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)
46 Downloads (Pure)


Background: 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). Methods: 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 PRS for depression could predict autoimmune disease status, and vice-versa. Results: We identified 28k cases of autoimmune diseases (pooling across 14 traits) and 324k autoimmune controls, and 65k cases of depression and 232k depression controls. The prevalence of depression was significantly higher in autoimmune cases compared to controls, and vice-versa. PRS for myasthenia gravis and psoriasis were significantly higher in depression cases compared to controls (p < 5.2x10-5, R2 <= 0.04%). PRS for depression were significantly higher in inflammatory bowel disease, psoriasis, psoriatic arthritis, rheumatoid arthritis and type 1 diabetes cases compared to controls (p < 5.8x10-5, R2 range 0.06% to 0.27%), and lower in coeliac disease cases compared to controls (p < 5.4x10-7, R2 range 0.11% to 0.15%). Conclusions: Consistent with the literature, depression was more common in individuals with autoimmune diseases compared to controls, and vice-versa. PRS showed some evidence for involvement of shared genetic factors, but the modest R2 values suggest that shared genetic architecture accounts for a small proportion of the increased risk across traits.
Original languageEnglish
JournalBiological Psychiatry: Global Open Science
Early online date25 Mar 2021
Publication statusE-pub ahead of print - 25 Mar 2021


Dive into the research topics of 'Investigating pleiotropy between depression and autoimmune diseases using the UK Biobank'. Together they form a unique fingerprint.

Cite this