Replication of candidate genes associated with Parkinon's disease and cutaneous malignant melanoma using whole-exome sequencing data.
Approved Research ID: 78210
Approval date: January 10th 2022
Parkinson's disease (PD) is a complex neurodegenerative disorder with many genetic factors. Several genetic changes have been shown to cause or increase a person's chance of getting PD, however many genetic factors are still unknown. Recent advances using next-generation sequencing data allow us to study rare (seen in very few people) genetic changes that are believed to play an important role in whether someone gets PD or not. Here, we propose to use the UKBiobank 200,000 whole-exome dataset to expand our current research and confirm our identified links of candidate genes coming from studying (i) the shared genetics between PD and cutaneous malignant melanoma (CMM) as suggested from increased chances of getting CMM in PD patients and vice versa; (ii) the role of having too many ultra-rare genetic variants that are known to be important in several other neurological diseases including Alzheimer's disease and schizophrenia; and (iii) to candidate genes affected by rare variants in early-onset PD cases that have long stretches of identical genetic changes in their genomes.
We expect to complete the replication analyses in a timeframe of 12 months. Any positively replicating candidate gene will support our current findings and will help us to prioritize genes for functional analysis, that will expand the current knowledge of PD pathogenesis, and serve as a potential guide for future therapies.
Our aim is to analyze the UKBiobank whole-exome cohort to replicate findings from our in-house candidate genes studies. With this dataset, we will confirm/reject candidate genes identified through different association analyses that seek to answer the following questions:
i) Does rare damaging variant burden underlie the shared increased risk to both cutaneous malignant melanoma and Parkinson's disease?
ii) Are genes/regions identified through ultra-rare variants and runs of homozygosity analyses associated with Parkinson's disease?
iii) Are epistatic interaction of common variants from genotyping data contributing to Parkinson's disease risk?