Gene4PD

Gene4PD integrates multilayered genetic data to prioritize Parkinson's disease (PD)–associated genes (PAGs) and to support analysis of their functional relationships and age-of-onset correlations.

Key Features:

• Integration of Multilayered Genetic Data: Consolidates data from over 3,000 studies including rare variants, copy-number variants, genome-wide association study (GWAS) data, differential expression genes, and differential DNA methylation genes.
• Prioritization of PAGs: Applies a weighted scoring system to prioritize 124 PAGs based on integrated evidence, with prioritized genes showing significant interconnectivity within a functional network.
• Functional Network Analysis: Uses permutation tests and protein-protein interaction networks to evaluate interconnectivity and functional enrichment among PAGs.
• Age of Onset (AAO) Correlation: Identifies genes associated with juvenile-onset (≤ 30 years), early-onset (30–50 years), and late-onset (> 50 years) categories and highlights AAO differences between loss-of-function and deleterious missense variants in genes such as GCH1, PINK1, PRKN, FBXO7, ATP13A2, and VPS13C.
• Integrated Database Links: Links prioritized PAGs and integrated datasets to 63 genomic data sources.
• Analytic Pipeline for Risk Variant Prioritization: Provides a pipeline to assist prioritization of risk variants associated with PD.

Scientific Applications:

• Gene discovery and prioritization: Support identification and ranking of candidate PD-associated genes from diverse genetic evidence.
• Functional and pathway analysis: Enable assessment of protein-protein interaction networks and pathway enrichment among prioritized genes.
• Age-of-onset and genotype–phenotype correlation: Facilitate analysis of AAO categories and variant-type differences across key PD genes.
• Therapeutic target identification and clinical interpretation: Inform selection of potential therapeutic targets and support diagnostic or prognostic genetic interpretation for PD.

Methodology:

Integrates rare variants, copy-number variants, GWAS, differential expression, and differential DNA methylation data from >3,000 studies; applies a weighted scoring system to prioritize 124 PAGs; performs permutation tests and protein-protein interaction network analysis; and implements a pipeline for risk variant prioritization.