Causal relationship between trunk and lower limb fat mass and interver tebral disc disorders: A two-sample mendelian randomization study
Author:
Huang Zhihao1, Tian Kunzong1, Tian Zhiqi2, Wang Yongming1, Jiang Yuting1
Affiliation:
1. Shandong Institute of Petroleum and Chemical Technology 2. Shengli Oilfield Central Hospital
Abstract
Abstract
Background: Intervertebral disc disorders (IVDDs) represent a significant cause of disability worldwide, with their etiology being multifactorial, including genetic predispositions and lifestyle factors such as obesity. The significance of body fat distribution in the onset of intervertebral disc disorders (IVDDs) has been recognized, yet the causal relationship remains poorly understood. This study aimed to elucidate the genetic underpinnings of this relationship by investigating the association between fat mass distribution in the trunk and low limb and the risk of IVDDs using Mendelian randomization (MR).
Methods: A comprehensive analysis was conducted using single nucleotide polymorphisms (SNPs) as instrumental variables to assess the genetic predispositions to increased fat mass in specific body regions (trunk and low limb) and their associations with IVDDs. The study began with reading 9,851,866 SNPs for trunk and low limb fat mass and 21,304,570 SNPs for IVDDs. Through a series of data cleaning steps, including linkage disequilibrium clumping, SNP merging, allele harmonization, and checks against the Phenoscanner database for confounding factors, the number of relevant SNPs was reduced to 353 for trunk fat mass, and 346 and 337 for left and right leg fat mass, respectively. The final causal analysis was performed using the inverse variance weighted (IVW) method and MR-Egger method, along with sensitivity analysis to test the robustness of the findings.
Results: The IVW method demonstrated a significant positive causal relationship between trunk fat mass and IVDDs (OR = 1.274, 95% CI: 1.186-1.368, p < 0.001), while the MR-Egger method showed no statistical significance (p = 0.214). However, both methods revealed a consistent and statistically significant association for low limb fat mass with IVDDs. Specifically, the IVW method indicated OR of 1.461 (95% CI: 1.330-1.605, p < 0.001) for left leg fat mass and 1.467 (95% CI: 1.331-1.618, p < 0.001) for right leg fat mass. The presence of heterogeneity and potential pleiotropy was assessed, with findings supporting the stability and reliability of the causal inferences.
Conclusion: This study confirmed a positive causal relationship between trunk and lower limb fat mass and the risk of IVDDs, highlighting the importance of considering body fat distribution in the prevention and management of IVDDs. The findings suggested that interventions aimed at reducing trunk and lower limb fat mass could potentially lower the risk of developing IVDDs. This research added valuable insights into the genetic and physiological links between body fat distribution and IVDDs, paving the way for targeted preventive strategies and therapeutic interventions.
Publisher
Research Square Platform LLC
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