Social isolation and loneliness, genetic predisposition, and their joint effects on chronic obstructive pulmonary disease risk: evidence from multiple cohort studies

Abstract Background To investigate the association between social isolation, loneliness, and COPD risk across different ethnic groups, while examining potential modification by genetic susceptibility. Methods This multi-database prospective cohort study includes 420,212 participants from the UK Biobank (UKB), 11,098 participants from the China Health and Retirement Longitudinal Study (CHARLS), and 8468 participants from the Health and Retirement Study in the United States (HRS). The polygenic risk scores (PRS) of COPD were calculated in the UKB cohort to characterize individual genetic risk. The association between social isolation, loneliness, and the risk of incident COPD was explored using Cox proportional hazards models. Mediation analysis was conducted to determine which potential variables mediate the relationship between social isolation, loneliness, and COPD. Results In the UKB cohort, over a median follow-up period of 13.6 years, 16,729 (3.6%) participants developed COPD. After adjusting for all covariates, participants who experience social isolation and loneliness are associated with a higher risk of COPD in UKB (social isolation [most vs least]: HR 1.255, 95% CI 1.197–1.317; loneliness [yes vs no]: HR 1.247, 95% CI 1.180–1.317). Consistent associations were also found in both the HRS (social isolation [yes vs no]: HR 1.231, 95% 1.022–1.483; loneliness [yes vs no]: HR 1.315, 95% CI 1.080–1.601) and CHARLS (social isolation [yes vs no]: HR 1.121, 95% 0.966–1.300; loneliness [yes vs no]: HR 1.326, 95% CI 1.193–1.475) cohorts. Conclusions Social isolation and loneliness are significantly associated with an increased risk of COPD among different ethnic groups. Among the European population, this association is independent of genetic risk.