Guanghua Deng, Yunjun Shu
Ya'an Hospital of Traditional Chinese Medicine, Ya'an, China.
Medicine (Baltimore). 2025 May 23;104(21):e42559. doi: 10.1097/MD.0000000000042559.
This study aims to explore the potential causal relationship between obesity and ankylosing spondylitis (AS) using the Mendelian randomization (MR) approach. Data were derived from a comprehensive genome-wide association study dataset. Genetic loci that demonstrated significant, independent associations with both obesity and AS in populations of European ancestry were selected as instrumental variables. Multiple MR analyses, including MR-Egger, weighted median, and inverse variance weighting, were employed to assess the causal impact of obesity on AS risk. To ensure reliability, heterogeneity, and multiplicity tests were conducted, and the robustness of the findings was evaluated through sensitivity analyses using the "leave-one-out" method. The inverse variance weighting analysis revealed an odds ratio (OR) of 0.95 with a 95% confidence interval of 0.76 to 1.19 and a P value of .653. These results indicated no significant causal link between obesity and AS development. Additionally, the heterogeneity and multiplicity tests showed no significant findings, while sensitivity analyses reinforced the consistency and robustness of the conclusions. This research did not find evidence of a causal relationship between obesity and the development of AS based on two-sample MR analysis and genetic data evaluation. However, the current study's limitations, including sample size and study design, highlight the need for future research with larger cohorts to further explore the intricate relationship between obesity and AS.
本研究旨在采用孟德尔随机化(MR)方法探索肥胖与强直性脊柱炎(AS)之间潜在的因果关系。数据来源于一个全面的全基因组关联研究数据集。在欧洲血统人群中,选择那些与肥胖和AS均表现出显著独立关联的基因座作为工具变量。采用了多种MR分析方法,包括MR-Egger、加权中位数和逆方差加权法,来评估肥胖对AS风险的因果影响。为确保可靠性,进行了异质性和多重性检验,并通过使用“留一法”的敏感性分析来评估研究结果的稳健性。逆方差加权分析显示比值比(OR)为0.95,95%置信区间为0.76至1.19,P值为0.653。这些结果表明肥胖与AS的发生之间不存在显著的因果联系。此外,异质性和多重性检验未显示出显著结果,而敏感性分析强化了结论的一致性和稳健性。基于两样本MR分析和遗传数据评估,本研究未发现肥胖与AS发生之间存在因果关系的证据。然而,当前研究的局限性,包括样本量和研究设计,凸显了未来需要开展更大样本队列研究以进一步探索肥胖与AS之间复杂关系的必要性。