Liu Jiayu, Liu Jiafeng, Li Lanjun, Li Wenju, Jiang Ziyang, Yin Gang, Zhang Yunling, Sun Yuan
Department of Neurology, Rizhao Central Hospital, Rizhao, 276800, Shandong, China.
Department of Neurology, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, 434400, Hubei, China.
BMC Neurol. 2025 Apr 16;25(1):163. doi: 10.1186/s12883-025-04184-7.
Age-related diseases, including Parkinson's disease and gastric cancer, substantially affect the global aging population. Previous observational research has suggested a potential association between Parkinson's disease and gastric cancer; however, findings regarding this aspect have been inconsistent. In the present study, we used data from genome-wide association studies to infer a causal relationship between Parkinson's disease and gastric cancer based on genetic variations.
We used the two-sample Mendelian randomization method to analyze data from the genome-wide association study catalog, including 482,730 and 476,116 patients with Parkinson's disease and gastric cancer, respectively. Inverse-variance weighting was used as the primary Mendelian randomization analysis. We conducted sensitivity analyses to evaluate heterogeneity and pleiotropy, followed by two-step Mendelian randomization to ascertain the latent mediator of the relationship between Parkinson's disease and gastric cancer.
Our results suggested a causal negative relationship between Parkinson's disease and gastric cancer. Heterogeneity and pleiotropy analyses confirmed the robustness of the inverse-variance weighting results. Furthermore, P2X6 was identified as a key factor mediating this negative causal relationship.
Patients with Parkinson's disease may have a lower risk of developing gastric cancer, with P2X6 serving as a significant mediating variable. These novel insights can aid the development of potential therapeutic targets for patients with Parkinson's disease or gastric cancer.
包括帕金森病和胃癌在内的与年龄相关的疾病对全球老年人口有重大影响。先前的观察性研究表明帕金森病与胃癌之间可能存在关联；然而，这方面的研究结果并不一致。在本研究中，我们利用全基因组关联研究的数据，基于基因变异推断帕金森病与胃癌之间的因果关系。
我们使用两样本孟德尔随机化方法分析来自全基因组关联研究目录的数据，分别包括482,730例帕金森病患者和476,116例胃癌患者。逆方差加权用作主要的孟德尔随机化分析。我们进行了敏感性分析以评估异质性和多效性，随后进行两步孟德尔随机化以确定帕金森病与胃癌之间关系的潜在中介因素。
我们的结果表明帕金森病与胃癌之间存在因果负相关关系。异质性和多效性分析证实了逆方差加权结果的稳健性。此外，P2X6被确定为介导这种负因果关系的关键因素。
帕金森病患者患胃癌的风险可能较低，P2X6作为一个重要的中介变量。这些新见解有助于为帕金森病或胃癌患者开发潜在的治疗靶点。
