Abstract
BackgroundDespite proposed aetiological mechanisms involving stress-induced inflammation and behaviour, population-level evidence linking social isolation and loneliness to asthma is lacking. Therefore, we aimed to examine the associations of social isolation, loneliness, and genetic predisposition with asthma risk in middle-aged and older adults, and to quantify the contribution of various risk factors.MethodsA total of 400,184 asthma-free participants were enrolled from the UK Biobank. Loneliness was evaluated using the short form of the Revised UCLA Loneliness Scale, and social isolation was assessed through a composite score based on key social network components. Asthma was evaluated using hospital inpatient records in UK Biobank. Genetic predisposition for asthma was characterized using weighted polygenic risk score (PRS). Cox proportional hazard models were utilized to assess the associations of social isolation and loneliness with the risk of asthma. The one-sample Mendelian randomization (MR) analysis was based on genome-wide association studies of UKB.ResultsOver an 11.6-years median follow-up, a total of 9453 new asthma cases were recorded. In the fully adjusted model, individuals with feelings of loneliness had a 1.27-fold higher risk of asthma (95% CI: 1.15-1.39) than those without. However, social isolation showed no significant association with asthma risk after several factor adjustments. No significant interactions of loneliness and asthma-PRS were detected. In the one-sample MR analyses, we observed suggestive genetic evidence supporting associations of feeling lonely, fewer leisure social activities, being willing to confide in others, and participating in more other group activities with asthma.ConclusionsOur findings suggest that loneliness, but not social isolation is a risk factor for asthma that is independent of various factors and genetic predisposition. Mendelian randomization provides suggestive evidence that loneliness and reduced social activity may be causal risk factors for asthma.