Objective:

To examine whether type 1 diabetes (T1D) is genetically or causally associated with Parkinson’s disease (PD).

Background:

Previous epidemiological and mendelian randomization studies demonstrated an association between PD and type 2 diabetes. However, there is no robust evidence on the association between T1D and PD.

Method:

To investigate the relationship between T1D and PD risk and progression we selected genome-wide association studies (GWASs) with participants of European ancestry and no overlapping samples. Given the complexity of its genetic architecture, we excluded the HLA locus from the analysis to minimize any potential biases. We performed mendelian randomization (MR) using the Two-Sample R package. We further used linkage disequilibrium score regression to explore the potential genetic correlations between PD and T1D. Finally, we conducted multi-tissue transcriptome-wide association analysis (TWAS) using the Unified Test for Molecular Signatures (UTMOST) software to discover common genetic signals between PD and T1D.

Results:

Mendelian randomization analysis indicated that T1D could potentially have a minor protective effect against PD, with an inverse-variance weighted (IVW) odds ratio (OR) of 0.97 (95% CI: 0.94-0.99; p=0.039). We also demonstrated minor protective effects of T1D for motor and cognitive decline in PD, with IVW estimates of 0.94 (95% CI: 0.88-0.99; p=0.044) and 1.50 (95% CI: 1.08-2.09; p=0.015), respectively. However, we found a negative genetic correlation between T1D and PD (rg=-0.17, p=0.016). Furthermore, we identified eight genes (CTSB, LAT, LRRC37A, LRRC37A2, R3HDM1, RAB7L1, RNF40 and WNT) through cross-tissue TWAS that were associated with both T1D and PD.

Conclusion:

To conclude, our results show a protective effect of T1D on PD risk and progression, which could be driven by potential pleiotropy. Larger comprehensive epidemiological studies are required to support further explore this association.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/potential-genetic-link-between-type-i-diabetes-and-parkinsons-disease/