What comes first: Heart rate variability changes or insomnia? A causal investigation using Mendelian randomization

Area of Science:

• Cardiology
• Sleep Medicine
• Genetics

Background:

• Heart rate variability (HRV) indicates autonomic nervous system function and is often altered in insomnia patients.
• Previous research linking HRV and insomnia is limited by small sample sizes and cross-sectional designs.
• Establishing causality between HRV and insomnia is crucial for developing effective sleep disorder interventions.

Purpose of the Study:

• To investigate the potential bidirectional causal relationship between HRV and insomnia.
• Utilize two-sample Mendelian randomization (MR) analysis for robust genetic insights.

Main Methods:

• Obtained genome-wide association study (GWAS) summary statistics for HRV traits (pvRSA/HF, RMSSD, SDNN) and insomnia.
• Performed bidirectional MR analyses using inverse variance weighted (IVW), MR-Egger, weighted median, and mode-based methods.
• Conducted sensitivity analyses to assess heterogeneity and horizontal pleiotropy.

Main Results:

• MR analysis indicated significant causal effects of HRV on insomnia risk for pvRSA/HF (OR=1.437, p=0.002) and SDNN (OR=1.910, p=0.022).
• These associations were robust across various MR methods and sensitivity analyses.
• Reverse MR analysis showed no significant causal effects of insomnia on HRV traits, suggesting unidirectional causality from HRV to insomnia.

Conclusions:

• This study provides genetic evidence that altered HRV causally increases insomnia risk.
• Insomnia does not appear to causally affect HRV, indicating a unidirectional relationship.
• Regulating HRV may serve as a potential therapeutic target for insomnia, improving sleep quality.