Li Huaxing, Su Guolan, Kang Weilan, Huang Weihao, Liu Aiwu, Zhang Meihui
Department of Neurology, Guangdong Tongjiang Hospital, Foshan, Guangdong Province, China.
Medicine (Baltimore). 2025 Aug 22;104(34):e43240. doi: 10.1097/MD.0000000000043240.
Patients with Parkinson disease (PD) have a higher risk of having constipation and vice versa. But so far it is not clear whether there is a causal relationship. Therefore, a 2-sample bidirectional Mendelian randomization study was performed to investigate the potential bidirectional association between constipation and PD. Independent genetic variants strongly associated with constipation were obtained from the FinnGen consortium. Data for PD were collected from the genome-wide association study summary data. We explored the causal relationship between constipation and PD using publicly available genome-wide association study data. Analysis of constipation's effect on PD identified 16 significant single nucleotide polymorphisms, all with strong instrumental validity. Genetic susceptibility analysis did not suggest any statistical significance between constipation and PD (odds ratio = 0.77, 95% confidence interval 0.57-1.04; P = .097). In the analysis of PD's impact on constipation, 20 significant single nucleotide polymorphisms were identified; however, genetic susceptibility analyses found no causal effect (odds ratio = 1.00, 95% confidence interval 0.97-1.04; P = .845). Our bidirectional Mendelian randomization analysis revealed no significant genetic association between constipation and PD in European populations, challenging the prevailing hypothesis of constipation as an early prodromal feature of PD. These null findings persisted across both forward and reverse causal directions. However, we cannot exclude the possibility of residual confounding through shared genetic architectures or undetected environmental covariables. Future studies incorporating larger multiethnic cohorts and comprehensive covariate adjustment are warranted to elucidate this association.
帕金森病（PD）患者患便秘的风险更高，反之亦然。但迄今为止，尚不清楚两者之间是否存在因果关系。因此，开展了一项双样本双向孟德尔随机化研究，以调查便秘与PD之间潜在的双向关联。与便秘密切相关的独立基因变异来自芬兰基因联盟。PD的数据则从全基因组关联研究的汇总数据中收集。我们利用公开可用的全基因组关联研究数据，探究便秘与PD之间的因果关系。对便秘对PD影响的分析确定了16个显著的单核苷酸多态性，所有这些多态性均具有很强的工具有效性。遗传易感性分析未显示便秘与PD之间存在任何统计学意义（优势比=0.77，95%置信区间0.57-1.04；P=0.097）。在分析PD对便秘的影响时，确定了20个显著的单核苷酸多态性；然而，遗传易感性分析未发现因果效应（优势比=1.00，95%置信区间0.97-1.04；P=0.845）。我们的双向孟德尔随机化分析表明，在欧洲人群中，便秘与PD之间不存在显著的基因关联，这对便秘是PD早期前驱特征这一普遍假设提出了挑战。这些阴性结果在正向和反向因果方向上均持续存在。然而，我们不能排除通过共享基因结构或未检测到的环境协变量产生残余混杂的可能性。未来有必要开展纳入更大规模多民族队列并进行全面协变量调整的研究，以阐明这种关联。
