Causal relationship between neuroticism and bone mineral density: A univariable and multivariable Mendelian...

Area of Science:

• Genetics
• Psychiatry
• Osteoporosis Research

Background:

• Observational studies suggest a link between psychiatric disorders and reduced bone mineral density (BMD).
• The specific causal relationship between neuroticism and BMD remains uncertain.

Purpose of the Study:

• To investigate the potential causal relationship between neuroticism and various measures of BMD using a bidirectional Mendelian randomization (MR) approach.
• To examine the direct causal effects of neuroticism on BMD, adjusting for common risk factors.

Main Methods:

• Utilized public genome-wide association study (GWAS) data for a two-sample bidirectional Mendelian randomization (MR) study.
• Employed inverse-variance weighted (IVW), weighted median, and MR-Egger methods for causal effect estimation.
• Conducted sensitivity analyses and multivariable MR to assess bias and direct effects, adjusting for BMI, smoking, and alcohol consumption.

Main Results:

• Genetically predicted higher neuroticism was significantly associated with reduced heel BMD (P < 0.0005).
• No significant causal association was found between neuroticism and forearm, femoral neck, lumbar spine, or total body BMD, possibly due to limited statistical power.
• The association between neuroticism and reduced heel BMD remained significant after adjusting for body mass index, smoking, and drinking.

Conclusions:

• Higher neuroticism shows a significant causal association with an increased risk of reduced heel bone mineral density.
• Further research is needed to understand the biological mechanisms and potential clinical applications for early screening and management of bone density issues.