Bidirectional causal relational between frailty and mental illness: a two-sample Mendelian randomization study.

Area of Science:

• Genetics and Public Health
• Epidemiology
• Psychiatry

Background:

• Observational studies suggest an association between frailty and mental illness (MI).
• The causal relationship between frailty and MI remains unclear.
• This study utilizes Mendelian randomization (MR) to assess bidirectional causality.

Purpose of the Study:

• To determine the causal relationship between frailty index (FI) and six types of MI: anxiety, depression, affective disorder, mania, schizophrenia, and obsessive-compulsive disorder (OCD).
• To investigate the potential bidirectional causality between FI and these mental illnesses.

Main Methods:

• Two-sample Mendelian randomization (MR) analyses were performed using summary statistics for FI and six MI.
• Primary analysis employed inverse variance weighting (IVW), MR-Egger regression, and weighted median methods.
• Robustness of results was assessed using Cochran's Q test, MR-Egger intercept, funnel plots, and leave-one-out analyses.

Main Results:

• Genetic predisposition to FI was associated with increased risk of anxiety, depression, and affective disorder.
• Reverse MR analysis indicated a causal relationship between anxiety, depression, affective disorder, and schizophrenia with FI.
• No significant causal relationship was found between FI and mania or OCD; results for schizophrenia and OCD require cautious interpretation due to inconsistencies.

Conclusions:

• A potential bidirectional causal relationship exists between frailty and anxiety, depression, and affective disorder.
• Schizophrenia is associated with an increased risk of frailty.
• Further research is needed to clarify the relationship between frailty and other mental illnesses.