Causal relationship between trunk and lower limb fat mass and intervertebral disc disorders: A 2-sample Mendelian...

Area of Science:

• Genetics
• Epidemiology
• Metabolic Health

Background:

• Intervertebral disc disorders (IVDDs) are a leading cause of global disability.
• Obesity and body fat distribution are recognized risk factors for IVDDs, but the causal link is not fully understood.
• Genetic factors influencing fat distribution may play a role in IVDD development.

Purpose of the Study:

• To investigate the causal relationship between fat mass distribution in the trunk and lower limbs and the risk of IVDDs.
• To elucidate the genetic underpinnings of the association between body fat and IVDDs using Mendelian randomization.
• To provide evidence for targeted prevention and management strategies for IVDDs.

Main Methods:

• Mendelian randomization (MR) analysis utilizing single nucleotide polymorphisms (SNPs) as instrumental variables.
• Analysis of large-scale genome-wide association study (GWAS) data for trunk fat mass, lower limb fat mass, and IVDDs.
• Application of inverse variance weighted (IVW) and MR-Egger methods, with sensitivity analyses to assess robustness and potential pleiotropy.

Main Results:

• A significant positive causal effect of trunk fat mass on IVDD risk was observed (OR=1.274, P<0.001).
• Significant positive causal effects of left and right lower limb fat mass on IVDD risk were consistently found (ORs ≈ 1.46, P<0.001).
• Sensitivity analyses supported the reliability of the causal inferences, despite some heterogeneity and potential pleiotropy.

Conclusions:

• Increased trunk and lower limb fat mass are causally associated with a higher risk of developing intervertebral disc disorders.
• Reducing fat mass in the trunk and lower limbs may be a viable strategy for lowering IVDD risk.
• These findings highlight the importance of body fat distribution in the context of IVDD prevention and management.