Objective: In this study, we investigated the association between rare variants in lysosomal storage disorders (LSDs) genes and Parkinson’s disease in large Chinese mainland cohorts.

Background: Recent years has witnessed an increasing number of studies indicating the lysosomal connection in Parkinson’s disease, and the most convinced important risk gene is the GBA. It indicated an important role of lysosomal dysfunction in Parkinson’s disease, which have also been replicated and reviewed by more researchers, especially in European population.

Method: We explored the association between rare variants of 54 lysosomal genes and Parkinson’s disease in 3879 patients and 2636 controls from Chinese mainland using whole-exome sequencing or whole-genome sequencing, which were analyzed by the optimized sequence kernel association test.

Results: We replicated the significant burden of rare putative LSDs gene variants in Parkinson’s disease patients. However, after excluding GBA, a suggestive association still persisted in the late-onset Parkinson’s disease cohort, but not in familial and early-onset Parkinson’s disease cohort. For the gene-based analysis, We confirmed the association between rare putative damaging variants in GBA and Parkinson’s disease. Furthermore, novel genes including GUSB, IDUA, KCTD7, MANBA, and NPC1 were found to be suggestively associated with early-onset Parkinson’s disease patients, whereas HYAL1, GALNS and NAGA were suggestively associated with late-onset Parkinson’s disease.

Conclusion: Our results revealed several novel risk genes and further replicated the importance of lysosomal mechanisms in Parkinson’s disease pathogenesis in Chinese mainland population.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/lysosomal-storage-disorder-genes-variants-in-parkinsons-disease-a-large-cohort-study-in-chinese-mainland-population/