Causal effects of the RANK-RANKL-OPG system and scoliosis: A bidirectional 2-sample Mendelian randomization study

Area of Science:

• Genetics and Bone Biology
• Epidemiology
• Biomedical Research

Background:

• Observational studies suggest a link between low bone mass and scoliosis risk.
• The RANK-RANKL-OPG system is implicated in bone metabolism and may influence scoliosis pathogenesis.

Purpose of the Study:

• To investigate the causal relationship between the RANK-RANKL-OPG system and scoliosis development using a Mendelian randomization approach.

Main Methods:

• Utilized genome-wide association study (GWAS) data for RANK, RANKL, and osteoprotegerin (OPG).
• Employed a bidirectional 2-sample Mendelian randomization (MR) framework with inverse variance weighting (IVW).
• Conducted meta-analysis and sensitivity analyses for robust findings.

Main Results:

• Inverse variance weighting (IVW) revealed no significant causal relationship between RANK or RANKL and scoliosis.
• Osteoprotegerin (OPG) demonstrated a protective effect against scoliosis (IVW P=.002; Meta-analysis P=1.428e-4).
• Inverse MR analysis confirmed no statistically significant causal relationship between scoliosis and the RANK-RANKL-OPG system.

Conclusions:

• Provides robust evidence for a causal link between decreased osteoprotegerin (OPG) levels and increased scoliosis susceptibility.
• No significant causal relationship was identified between scoliosis and the RANK or RANKL components of the system.
• Establishes a foundation for further research into scoliosis pathophysiology and targeted therapeutic strategies.