P1123 Social isolation, loneliness, and incident inflammatory bowel disease: results from a large prospective cohorts and Mendelian randomization

Background Background Social isolation and loneliness pose significant public health challenges globally. The objective of this study is to investigate the association between social isolation, loneliness, and the risk of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD). Methods Methods 275,157 UK adults from the UK Biobank (UKB) was analyzed. The exposures of interest were social isolation and loneliness. Social isolation was measured by the frequency of meeting family/friends, leisure and social activity, and communal/solitary living. Loneliness was evaluated by the subjective feeling of loneliness and the willingness to confide in others. The primary endpoint was incident IBD, including UC and CD. The twosample Mendelian randomization (MR) analysis was based on the genome-wide association studies of UKB and the a nonoverlapping European ancestry GWAS study. Results Results The UKB cohort study documented 1,565 IBD (1063 UC and 492 CD) cases during a mean follow-up of 13.49 years. Social isolation and loneliness showed significant associations with an elevated risk of IBD in UKB (social isolation [moderate vs least]: aHR 1.13, 95% CI 1.02-1.26; social isolation [most vs least]: aHR 1.31, 95% CI 1.01-1.70; loneliness [yes vs no]: aHR 1.29, 95% CI 1.04-1.60). These associations were evident among moderate genetic susceptibility to IBD. Social isolation and loneliness jointly increase the risk of IBD onset, with an aHR of 1.60 (95% CI 1.21-2.12). Two-sample MR analyses determined that engaging in fewer leisure/social activities (OR 3.42, 95% CI 1.55-7.58; 3.32, 95% CI 1.29-8.55; 3.09, 95% CI 1.35-7.07) were associated with increased IBD, UC and CD risk, whereas more activities-sports club or gym (OR 0.37, 95% CI 0.15-0.88) was associated with reduced IBD risk. Conclusion Conclusion Social isolation and loneliness are each associated with an elevated risk of IBD especially for individuals with a moderate genetic risk for IBD, with MR analyses suggesting potential causal links. The findings highlight the importance of promoting initiatives to address social isolation and loneliness as part of IBD prevention strategies.