Sleep and circadian disorders as risk factors for autoimmune disease: A population-based study

Sleep and circadian disruption have been increasingly linked to immune dysregulation, yet population-level associations with autoimmune disease remain underexplored. We examined whether delayed sleep phase disorder (DSPD), obstructive sleep apnea (OSA), primary insomnia, and hypersomnia were associated with autoimmune conditions in a large, diverse U.S. cohort.

Data were drawn from the All of Us Research Program Registered Tier Dataset v8. Participants were categorized into sleep disorder groups based on clinical diagnoses, with regular sleepers serving as controls. Autoimmune disease was defined using SNOMED-coded records. DSPD and primary insomnia were analyzed using rare disease logistic regression; OSA and hypersomnia were analyzed using 1:5 propensity score matching. Adjusted logistic regression models included age, sex at birth, race, ethnicity, income, BMI, and chronic inflammatory diagnosis. E-values assessed robustness to unmeasured confounding.

All four sleep disorder groups showed significantly higher odds of autoimmune diagnosis relative to regular sleepers (p < 2.2 × 10^-16). Adjusted odds ratios were: DSPD (OR = 0.26; 95 % CI: 0.15-0.45), OSA (OR = 0.46; 95 % CI: 0.41-0.52), primary insomnia (OR = 0.46; 95 % CI: 0.41-0.52), and hypersomnia (OR = 0.48; 95 % CI: 0.46-0.50). Older age, female sex, and chronic inflammation were associated with higher autoimmune prevalence. Asian race and BMI were inversely associated with autoimmune risk; higher income was unexpectedly associated with greater autoimmune diagnosis.

Distinct sleep phenotypes were associated with autoimmune conditions. These associations may reflect shared or bidirectional links between sleep disruption and immune dysregulation.