Causality of multiple serum metabolites on emotional lability: A two-sample Mendelian randomization study

Area of Science:

• Psychiatry
• Metabolomics
• Genetics

Background:

• Emotional lability (EL) is a key feature of psychiatric disorders, causing significant functional impairment.
• The underlying causes of EL are not well understood, limiting effective interventions.
• Metabolic dysregulation is increasingly implicated in the pathophysiology of mental health conditions.

Purpose of the Study:

• To investigate the causal relationship between genetically determined serum metabolite levels and emotional lability (EL).
• To identify potential metabolic biomarkers for EL using a Mendelian randomization approach.

Main Methods:

• Employed a comprehensive Mendelian randomization (MR) design.
• Utilized summary-level data from large genome-wide association studies (GWAS) for serum metabolites and EL.
• Conducted rigorous sensitivity analyses to assess the robustness of findings, including heterogeneity and pleiotropy.

Main Results:

• Identified 30 metabolites with potential causal associations with EL out of 1400 analyzed.
• Hydrocinnamate showed a causal association with an increased risk of EL.
• Glycolithocholate and 3β-hydroxy-5-cholenoic acid were associated with a decreased risk of EL.

Conclusions:

• This Mendelian randomization study provides evidence for a causal link between specific metabolites and EL.
• Hydrocinnamate, glycolithocholate, and 3β-hydroxy-5-cholenoic acid may serve as potential metabolic biomarkers for EL.
• These identified metabolites represent promising therapeutic targets for managing EL in psychiatric conditions.