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

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).