Genetic Analysis of ZNF Protein Family Members for Early-Onset Parkinson's Disease in Chinese Population

Functional and genetic studies have identified association between several Zinc finger (ZNF) proteins and Parkinson's disease (PD). However, most of them were still awaiting further replications, especially in the Asian population. Here, we systematically selected PD-relevant ZNF genes and analyzed the genetic associations between these ZNFs and PD in a large Chinese PD cohort. We identified rare variants (minor allele frequency < 0.01) in 743 unrelated patients with early-onset PD (EOPD, age at onset < 50 years) using whole exome sequencing and evaluated the association between rare variants and EOPD at both allele and gene levels. Totally 91 rare variants were identified in ZNF746, ZNF646, ZNF184, ZNF165, ZND219, and GLIS1. One variant p.R373H in ZNF219 and two variants p.G161D and p.R158H in ZNF746 were significantly associated with EOPD, and gene-based burden analysis showed enrichment of rare variants of ZNF746 in EOPD. Our findings build up the connection between ZNF746 and PD from a genetic perspective for the first time, supplement current understanding for the genetic role of ZNFs in EOPD, and broaden the mutation spectrum in PD.