Family Analysis Working Group
Under the Monogenic Network, this new working group focuses on family-based genetic analysis to uncover novel causal genes for Parkinson's disease (PD).
About the Family Analysis Working Group
The Family Analysis Working group is co-led by Joanne Trinh and Niccolò Mencacci, leveraging pedigrees from multi-generational PD families to identify rare variants segregating with disease, complementing population-based studies.
Why Family-Based Analysis?
Family studies excel at detecting monogenic causes missed by sporadic case-control designs, as affected relatives share genetic backgrounds that amplify rare variant signals. Methods include linkage analysis, whole-genome sequencing of trios/pedigrees, segregation testing, and burden analysis of ultra-rare variants, revealing genes like those in early-onset or familial PD cohorts with yields up to 15% in enriched families
Milestones
Completed
- Segregation analysis performed for 57 families analyzed for coding variants
- Long-read whole-genome sequencing (WGS) performed for 100 probands
Active
- Family-based WGS analysis workflows, prioritizing unsolved early-onset and familial PD cases.
- Rare-variant association and segregation testing (coding/non-coding) across pedigrees to pinpoint high-penetrance monogenic causes.
- In-house lab validation and further segregation analysis of interesting candidate variants
- Expansion of families with a history of PD through the buddy system within GP2
- Long-read WGS for complex repeats in positive family histories
- Family-based association analysis on rare variants
- Case-control analysis of candidate variants from segregation work