Association between loneliness, social isolation, and frailty: A two-sample Mendelian randomization

Abstract

Abstract Objective: This study aimed to examine the causal relationship between loneliness, social isolation, and frailty using Mendelian Randomization (MR) analysis. Methods: Data were obtained from a large-scale genome-wide association study (GWAS) of a European-descent population. Variables included frailty index (FI), two loneliness variables (Feeling lonely, able to confide), and three social isolation variables (Frequency of friend/family visits, number in household, no leisure/social activities).The inverse variance weighting (IVW) method was set as the primary MR analysis, with MR-Egger and weighted median methods employed as complementary approaches. Cochran’s Q test, the MR-Egger intercept test, and MR-PRESSO methods were used to evaluate the robustness of MR results. Bonferroni corrected P values <0.01 were considered statistically significant. Results: Genetic predisposition to feeling lonely (IVW: odds ratio [OR]=1.47; 95% confidence interval [CI]=1.34 to 1.60; P<0.001) and no leisure or social activities (IVW: OR=1.78; 95% CI=1.50 to 2.11; P<0.001) were significantly associated with increased FI. In addition, the genetically predicted ability to confide was positively associated with decreased FI (IVW: OR=0.91; 95% CI=0.87 to 0.95; P<0.001). There was no statistically significant causal association between the number in the household, frequency of friend/family visits, and the risk of frailty. Conclusion: This MR study provides evidence of the causal relationship between loneliness, social isolation, and frailty from a genetic perspective and highlights the importance of decreasing social isolation in the development of frailty prevention and intervention programs.