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The Casual Association Inference for the Chain of Falls Risk Factors-Falls-Falls Outcomes: A Mendelian Randomization

Jia-Xin Wu1,2,3, Fei-Yan Deng1,2,3, Shu-Feng Lei1,2,3,4

  • 1Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou 215123, China.

Healthcare (Basel, Switzerland)
|July 14, 2023
PubMed

Insights

This study used Mendelian randomization to identify causal risk factors for falls, including osteoporosis, BMI, and sleeplessness. It also confirmed falls increase risks for fractures, stroke, and epilepsy.

Area of Science:

  • Epidemiology
  • Genetics
  • Gerontology

Background:

  • Previous studies noted associations between fall risk factors and outcomes but lacked causal evidence.
  • Understanding the causal pathways of falls is crucial for developing effective prevention strategies.

Purpose of the Study:

  • To investigate the causal relationships between various risk factors and falls.
  • To determine the causal impact of falls on subsequent clinical outcomes.
  • To elucidate the mediating role of falls in the development of adverse health events.

Main Methods:

  • Mendelian randomization (MR) and multivariate Mendelian randomization (MVMR) analyses were employed.
  • Data were sourced from UK Biobank participants of White European ancestry (40-69 years).
  • Mediation analyses were conducted to explore indirect effects.

Main Results:

  • Osteoporosis, BMI, sleeplessness, rheumatoid arthritis, waist, and hip circumference were identified as causal risk factors for falls.
  • Increased fall risk significantly elevated the risk of fractures, stroke, and epilepsy.
  • Sleeplessness emerged as a key risk factor for falls in MVMR analysis.
  • Mediation analyses confirmed falls mediate the relationship between risk factors (e.g., sleeplessness, hip circumference) and outcomes (e.g., fracture, epilepsy).

Conclusions:

  • This study establishes causal links between specific risk factors and falls, and between falls and subsequent adverse health outcomes.
  • The findings provide a foundation for targeted interventions to reduce fall-related morbidity and mortality.
  • Three causal chains (risk factors → falls → outcomes) were elucidated, offering a comprehensive understanding of fall pathophysiology.
Keywords:
Mendelian randomizationcausal relationshipfalls

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