Association between frailty and common psychiatric disorders: A bidirectional Mendelian randomization study

There is growing interest in exploring the relationship between frailty and common psychiatric disorders. However, there have been limited reports on the genetic variation level of frailty with psychiatric disorders.

We conducted large-scale Two-sample Mendelian randomization (MR) analyses to examine whether there is an association between frailty and common psychiatric disorders (bipolar disorder [BD], major depressive disorder [MDD], schizophrenia, and suicide or other Intentional self-harm). We employed multiple MR approaches to conduct the MR analysis, including MR-Egger, weighted median, and random-effect inverse variance weighted (IVW). The IVW method served as the primary analysis. Heterogeneity testing and sensitivity analysis were also conducted in the MR study.

The MR results denoted that frailty was associated with an increased risk of BD (odds ratio (OR) =1.60, P_IVW = 0.017), MDD (OR = 2.04, P_IVW < 0.001), schizophrenia (OR = 1.91, P_IVW = 0.005), and suicide or other Intentional self-harm (OR = 1.77, P_IVW < 0.001). For reverse analysis, we observed no significant association between psychiatric disorders and the risk of frailty. These results remained consistent across sensitivity assessments.

Our research indicates a potential unidirectional causal relationship, suggesting that frailty may serve as a risk factor for certain common psychiatric disorders. These findings carry important for implications for psychiatric disorders and frailty patient care.