Multi-ancestry rare variant burden analysis of E3 ubiquitin ligase genes in Parkinson's disease

Abstract

E3 ubiquitin ligases regulate protein degradation through the ubiquitin-proteasome system and have been implicated in early-onset Parkinson's disease (EOPD). We performed a multi-ancestry rare variant burden analysis of seven E3 ubiquitin ligase genes (HERC1, IRF2BPL, KMT2D, RAPSN, RNF168, RNF216, TRIM2) using GP2 Release 11 WGS data from 17,928 PD patients (including 6,659 EOPD) and 8,977 controls across five major ancestry groups (African, Central Asian, East Asian, European, and Middle Eastern). We did not identify any association between gene based rare burden and PD, using the optimised sequence kernel association test (SKAT-O).

Progression GWAS followed by functional characterization implicates E3 ubiquitin ligase TRIM2 as a potential genetic modifier of Parkinson’s disease progression
Ameya S. Kulkarni, Dan Apicco, Saleh Tamim +14
Scientific Reports1 Sep 2026Peer-reviewedCC BYFull textNeurologyDOAJ
Resting-state cortical alpha frequency in Parkinson’s disease and multiple system atrophy: associations with diagnosis, age, and symptom burden
Daichao Chen, Huada Tang, Yanfei Pan +11
Frontiers in aging neuroscience16 Oct 2026Peer-reviewedCC BYFull textGeneral medicineEurope PMC
Parkinson's disease-associated LRRK2 risk variant, G2385R, enhances Rab substrate phosphorylation and impairs neuronal integrity.
An Phu Tran Nguyen, Roger Moser, Nicole Bryant +3
Human molecular genetics1 Sep 2026Peer-reviewedCC BY-NCFull textNeurologyEurope PMC
LRRK2 G2019S variant is associated with transcriptional changes in Parkinson’s disease human myeloid cells under proinflammatory environment
Elisa Navarro, Anastasia G. Efthymiou, Daniele Mattei +22
Journal of Neuroinflammation8 Aug 2026Peer-reviewedCC BY 4.0Full text6 citedNeurologyPMC
Wearable Evidence Linking Dyskinesia Burden to Sleep Quality in Parkinson's Disease.
Viktoria Azoidou, Essa Bhadra, Ellen Camboe +11
Movement disorders clinical practice1 Nov 2026Peer-reviewedCC BYFull textNeurologyEurope PMCPMC

Cite

BibTeX RIS

BibTeX

@misc{velasquezmendez2026multiancestry,
  title = {{Multi-ancestry rare variant burden analysis of E3 ubiquitin ligase genes in Parkinson's disease}},
  author = {K. L. Velasquez-Mendez and D. F. Santos-Gil and M. T. Perinan and K. Senkevich and the Global Parkinson's Genetic Program (GP2)},
  howpublished = {medRxiv},
  year = {2026},
  month = nov,
  doi = {10.64898/2026.11.01.26366966},
  url = {https://www.medrxiv.org/content/10.64898/2026.11.01.26366966v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Multi-ancestry rare variant burden analysis of E3 ubiquitin ligase genes in Parkinson's disease
AU  - K. L. Velasquez-Mendez
AU  - D. F. Santos-Gil
AU  - M. T. Perinan
AU  - K. Senkevich
AU  - the Global Parkinson's Genetic Program (GP2)
PY  - 2026
DA  - 2026/11/01
PB  - medRxiv
DO  - 10.64898/2026.11.01.26366966
UR  - https://www.medrxiv.org/content/10.64898/2026.11.01.26366966v1
AB  - E3 ubiquitin ligases regulate protein degradation through the ubiquitin-proteasome system and have been implicated in early-onset Parkinson's disease (EOPD). We performed a multi-ancestry rare variant burden analysis of seven E3 ubiquitin ligase genes (HERC1, IRF2BPL, KMT2D, RAPSN, RNF168, RNF216, TRIM2) using GP2 Release 11 WGS data from 17,928 PD patients (including 6,659 EOPD) and 8,977 controls across five major ancestry groups (African, Central Asian, East Asian, European, and Middle Eastern). We did not identify any association between gene based rare burden and PD, using the optimised sequence kernel association test (SKAT-O).
ER  -

Abstract

Related

Cite