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Human Genetics01:28

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Related Experiment Video

Updated: May 31, 2025

Measuring Frailty in HIV-infected Individuals. Identification of Frail Patients is the First Step to Amelioration and Reversal of Frailty
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Exploring the bidirectional causality between neuroticism and frailty: a Mendelian randomization analysis.

Yuhang Xing1, Rui Pu2, Mengdie Fu2

  • 1Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.

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|January 25, 2025
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Summary

This study reveals a two-way causal link between neuroticism and frailty using genetic data. Higher neuroticism increases frailty risk, and frailty also elevates the risk of neuroticism.

Keywords:
FrailtyMendelian randomizationMental disorderNeuroticism

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Area of Science:

  • Genetics
  • Psychiatry
  • Gerontology

Background:

  • Epidemiological studies link neuroticism to physical health.
  • The connection between neuroticism and frailty requires further investigation.
  • This study addresses the unconfirmed relationship between neuroticism and frailty.

Purpose of the Study:

  • To investigate the causal relationship between neuroticism and frailty.
  • To employ a bi-directional two-sample Mendelian randomization (MR) approach.
  • To explore the genetic underpinnings of the neuroticism-frailty connection.

Main Methods:

  • Utilized UK Biobank and Swedish TwinGene data for genome-wide association studies (GWAS).
  • Selected independent genetic variants as instrumental variables for neuroticism and frailty.
  • Applied inverse variance weighted (IVW), MR-Egger, and other MR analyses.

Main Results:

  • Neuroticism showed a positive causal effect on frailty risk (OR=1.627, P<0.001).
  • Frailty demonstrated a causal effect on increased neuroticism risk (OR=1.270, P<0.001).
  • Steiger tests confirmed the absence of reverse causation bias.

Conclusions:

  • Established a bi-directional causal relationship between frailty and neuroticism through genetic evidence.
  • Confirmed positive causal links in both directions: neuroticism to frailty and frailty to neuroticism.
  • Highlights the complex interplay between psychological traits and aging-related health conditions.