Social isolation, loneliness and subsequently developing risk for autoimmune diseases: A prospective study from UK Biobank

Social isolation and loneliness may be associated with neuroendocrine and inflammatory alterations, but prospective associations with autoimmune disease remain unclear. We examined these associations and joint risk patterns with genetic susceptibility.

This prospective study included 454,529 UK Biobank participants without any of 19 autoimmune diseases at baseline. Level of social isolation was assessed using a three-item score based on social contact, participation in social activities, and living situation; participants were categorized as least, moderately, or most isolated. Level of loneliness was assessed using a two-item score based on feeling lonely and ability to confide; participants were categorized as lonely or non-lonely. Outcomes included overall autoimmune disease, a composite of the 19 diseases, and each disease separately. Cox models estimated associations, including analyses with outcome-matched polygenic risk scores (PRS).

During a median follow-up of 13.2 years, 39,101 participants developed autoimmune disease. Compared with the least isolated group, HRs were 1.07 (95% CI 1.05-1.09) and 1.15 (95% CI 1.11-1.19) for the moderately and most isolated groups, respectively. Lonely participants had a higher risk than non-lonely participants (HR 1.19, 95% CI 1.14-1.24). Joint analyses showed higher risks with adverse social exposures and high PRS, whereas FDR-corrected analyses provided limited evidence of interaction across PRS levels for overall autoimmune disease.

Social isolation and loneliness were associated with modestly higher autoimmune disease risk, but causal and population-level interpretations are not warranted.