Potential protective link between type I diabetes and Parkinson’s disease risk and progression

Background Epidemiological studies suggested an association between Parkinson’s disease (PD) and type 2 diabetes, but less is known about type 1 diabetes (T1D) and PD. Objectives To explore the association between T1D and PD. Methods We used Mendelian randomization, linkage disequilibrium score regression and transcriptome wide association analysis (TWAS) to examine the association between PD and T1D. Results Mendelian randomization showed a potentially protective role of T1D for PD risk (inverse-variance weighted (IVW); OR (95% CI) 0.97 (0.94-0.99); p=0.039), as well as motor (IVW; 0.94 (0.88-0.99); p=0.044) and cognitive progression (IVW; 1.50 (1.08-2.09); p=0.015). We further found negative genetic correlation between T1D and PD (rg=-0.17, p=0.016), and identified nine genes in cross-tissue TWAS that were associated with both traits. Conclusions Our results suggest a potential genetic link between T1D and PD risk and progression. Larger comprehensive epidemiological and genetic studies are required to validate our findings. ### Competing Interest Statement ZGO received consultancy fees from Lysosomal Therapeutics Inc. (LTI), Idorsia, Prevail Therapeutics, Inceptions Sciences (now Ventus), Ono Therapeutics, Denali and Deerfield. Dr. Noyce reports grants from Parkinson’s UK, Barts Charity, Cure Parkinson’s, NIHR, Innovate UK, Virginia Keiley benefaction, Alchemab, Aligning Science Across Parkinson’s Global Parkinson’s Genetics Program (ASAP-GP2) and Michael J Fox Foundation. Consultancy and personal fees from AstraZeneca, AbbVie, Profile, Roche, Biogen, UCB, Bial, Charco Neurotech, uMedeor, Alchemab, and Britannia, outside the submitted work. The rest of the authors have nothing to report. ### Funding Statement This study was financially supported by grants from the Michael J. Fox Foundation, the Canadian Consortium on Neurodegeneration in Aging (CCNA), the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives initiative (HBHL), and Parkinson Canada. ### 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: We used only publicly available data in the current study. References for GWASs and packages for analysis are detailed in the Methods section. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All results are reported in the tables or attached in the supplementary data.