Identification of Novel Genetic Loci for Parkinson’s Disease Using Whole-Exome and Whole-Genome Sequencing

Background: Parkinson’s disease (PD) is a prevalent neurodegenerative disorder characterized by a multifaceted genetic foundation. We hypothesized that combining whole-genome sequencing (WGS) with whole-exome sequencing (WES) in a multi-generational family affected by PD could identify rare and novel variants of genes associated with PD.

Methods: This study included a family showing multiple members affected by PD and exhibiting an apparent dominant inheritance pattern. Seventeen family members were genotyped by WES and 6 of them was additionally analyzed by WGS. The common variants were validated by Sanger sequencing.

Results: Forty-seven genes that may be associated with PD were identified by co-separation analysis, clustering analysis, correlation analysis of resequencing data, and 2 of them were common. For these two genes, polymerase chain reaction (PCR) and Sanger sequencing were performed in family members and quantitative PCR (qPCR) was conducted in 6 sporadic PD patients and 6 controls to detect mRNA expression. It was found that the Ddx56 mutation frequency (chr7: 44610462) was significantly different between PD and control in the family. Additionally, the DEAD-box helicase 56 (Ddx56) gene was downregulated in PD patients, outside the family members, while Ccdc42 mutation frequency and mRNA expression had no significant difference.

Conclusion: Therefore, it was speculated that the mutation of Ddx56 in exon (chr7: 44610462) might be related to the occurrence of PD.

Cite this article as: Xu Q, Zhou M, Ni H, et al. Identification of novel genetic loci for parkinson’s disease using whole-exome and whole-genome sequencing. Psychiatry Clin Psychopharmacol. Published online April 16, 2025. doi: 10.5152/pcp.2025.24889