Does Toxoplasma gondii infection have a causal impact on human psychopathology? A Mendelian randomization analysis

Abstract Toxoplasma gondii (T. gondii) is a prevalent zoonotic parasite that has been implicated in influencing human psychiatric disorders and risk-taking behaviors. Using genome-wide association study (GWAS) data, we conducted two-sample Mendelian randomization (MR) analyses to investigate the potential causal relationship between T. gondii infection and the aforementioned psychiatric disorders and risk-taking behaviors. Contrary to previous epidemiological evidence, our MR analyses do not support a significant causal association between T. gondii infection and the studied psychiatric disorders or risk-taking behaviors. These findings challenge the hypothesis that chronic T. gondii influences human psychopathology and behavior. Competing Interest Statement X.L. is a co-founder of Genos Bioinformatics. K.K. is a consultant to Regeneron, an inventor on a patent application filed by the University of South Florida for 33D swabs. K.K. has a leadership or fiduciary role in the IDSA Board of Directors, ParaFrap, and Sanford Guide. Funding Statement This study was funded by the startup funding provided by the College of Public Health, University of South Florida, to XL. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The data supporting the findings of this study are openly available in the Integrative Epidemiology Unit OpenGWAS project (IEU) at https://gwas.mrcieu.ac.uk/. Reference numbers are provided in Table 2 of the manuscript. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data availability statement The data supporting the findings of this study are openly available in the Integrative Epidemiology Unit OpenGWAS project (IEU) at https://gwas.mrcieu.ac.uk/. Reference numbers are provided in Table 2 of the manuscript.