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Research
Huifang Shang
West China Hospital of Sichuan University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0947-1151
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This work is licensed under a CC BY 4.0 License. Read Full License
Background
Dysfunction of the ubiquitination proteasome system (UPS) is important in the pathogenesis of Parkinson’s disease (PD). Patients with early onset PD (EOPD) are more susceptible to genetic factors. We systematically examined the overlaps between E3 ubiquitin ligase genes and EOPD.
Methods
A total of 695 EOPD patients were sequenced with whole exome sequencing. Aggregate burden for rare variants (Minor allele frequency <0.001 and <0.0001) in a total of 44 E3 ubiquitin ligase genes causing disorders involved in the nervous system were analyzed.
Results
There was significant enrichment of the rare and rare damaging variants in the E3 ubiquitin ligase genes in EOPD patients. Detailly, at the gene-based level, the strongest associations were found in HERC1, IRF2BPL, KMT2D, RAPSN, RLIM, RNF168 and RNF216.
Conclusion
Our findings highlight the importance of the UPS mechanism in the pathogenesis of PD from the genetic perspective. Moreover, our study also expanded the susceptible gene spectrum for PD.
Keywords
E3 ubiquitin ligase, Early onset Parkinson’s disease, burden, association
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This is a preprint. It has not completed peer review.
Research
Huifang Shang
West China Hospital of Sichuan University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0947-1151
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 03 Mar, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Dysfunction of the ubiquitination proteasome system (UPS) is important in the pathogenesis of Parkinson’s disease (PD). Patients with early onset PD (EOPD) are more susceptible to genetic factors. We systematically examined the overlaps between E3 ubiquitin ligase genes and EOPD.
Methods
A total of 695 EOPD patients were sequenced with whole exome sequencing. Aggregate burden for rare variants (Minor allele frequency <0.001 and <0.0001) in a total of 44 E3 ubiquitin ligase genes causing disorders involved in the nervous system were analyzed.
Results
There was significant enrichment of the rare and rare damaging variants in the E3 ubiquitin ligase genes in EOPD patients. Detailly, at the gene-based level, the strongest associations were found in HERC1, IRF2BPL, KMT2D, RAPSN, RLIM, RNF168 and RNF216.
Conclusion
Our findings highlight the importance of the UPS mechanism in the pathogenesis of PD from the genetic perspective. Moreover, our study also expanded the susceptible gene spectrum for PD.
Figure 1
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