Social isolation, loneliness, genetic susceptibility, and the risk of hypothyroidism.

This study aimed to explore associations between social isolation, loneliness, and hypothyroidism risk, and whether genetic susceptibility modifies these links. It enrolled 434,628 hypothyroidism-free participants from the UK Biobank. Social isolation was assessed via 3 dichotomous questions, loneliness via 2 revised UCLA Loneliness Scale questions, and hypothyroidism cases via hospital/death records. Hypothyroidism polygenic risk scores (PRSs) were calculated using related genetic loci, with Cox proportional hazards models for analysis. Over a median 12.3-year follow-up, 9,873 hypothyroidism cases occurred. Demographically adjusted models showed social isolation (HR = 1.25, 95% CI 1.17-1.33) and loneliness (HR = 1.38, 95% CI 1.27-1.50) linked to higher risk. After full adjustment, only loneliness remained significant (HR = 1.12, 95% CI 1.02-1.24), while social isolation's association became insignificant. No significant interactions between loneliness/social isolation or loneliness/PRS were found. Joint analysis revealed highest risk in those with high PRS and loneliness. Findings indicate loneliness, not social isolation, is an independent hypothyroidism risk factor, regardless of genetic susceptibility and other factors.