Association of Social Relationships and Genetic Risk With Frailty

To investigate the association between social relationships and their changes with frailty among older adults, and whether genetic risk modifies these associations.

This study included 11,559 older adults (mean age 80.1 years) from the Chinese Longitudinal Healthy Longevity Survey. Social relationships were categorized into three dimensions: social activities, social networks, and social support, each classified as favorable or unfavorable groups. Changes in social relationships were assessed at two time points. The polygenic risk score (PRS) was constructed using 59 single-nucleotide polymorphisms associated with frailty. Cox proportional hazards models were used to assess the effects of social relationships and their changes, and PRS on frailty. Two-sample Mendelian randomization identified causal associations.

During a median follow-up of 5.4 years, 4773 participants developed frailty. Unfavorable social relationships, particularly in social activities and social networks, were associated with increased frailty risk, with stronger effects in those with high genetic risk. Mendelian randomization revealed their harmful effects on frailty. An additive interaction between social relationships and genetic risk on frailty was observed. Combined unfavorable social relationships and high genetic risk increased frailty risk by 39% (HR: 1.39, 95% CI: 1.23-1.57). Persistent unfavorable relationships further increased frailty risk by 58% in those with high genetic risk (HR: 1.58, 95% CI: 1.27-1.97).

Unfavorable social relationships increase frailty risk, particularly for individuals with high genetic susceptibility. Persistent unfavorable relationships further increase this risk over time, with the highest frailty risk observed in those with both persistent unfavorable social relationships and high genetic risk.