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

Rare variant burden in seven E3 ubiquitin ligase genes is not associated with Parkinson’s disease in a multi-ancestry cohort of 17,928 patients and 8,977 controls.

• Why it matters: E3 ubiquitin ligases are linked to protein degradation and have been implicated in early-onset Parkinson’s disease, but gene-level rare variant effects across ancestries remain unclear.
• What they did: The study analyzed GP2 Release 11 whole-genome sequencing data for HERC1, IRF2BPL, KMT2D, RAPSN, RNF168, RNF216, and TRIM2 in 17,928 PD cases (including 6,659 EOPD) and 8,977 controls using SKAT-O.
• The result: No gene-based rare variant burden signal was detected, suggesting these seven E3 ubiquitin ligase genes do not contribute detectable rare-variant risk to PD in this dataset.

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