Constipation and Parkinson disease: A 2-sample bidirectional Mendelian randomization analysis

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.