Despite the identification of genes and GWAS loci implicated in PD liability, there is still no successful implementation of genetic findings on practical treatment decisions for Parkinson's disease. In this project, we will take advantage of our novel mDA neuron differentiation protocols, the accessibility of validated PD-iPSCs, and corresponding isogenic controls, as well as the expertise in scRNA-seq, to investigate the molecular phenotype of distinct genetic forms of PD. We aim to investigate the molecular and cellular mechanisms underlying familial and sporadic PD and their contribution to both motor and non-motor features. This will enable us to ① define different forms of PD based on the alterations in gene expression and their involvement in specific molecular pathways, ② resolve subtypes of mDA neurons in which genetic variants influence PD onset, and progression, ③ identify possible biomarkers of PD progression as well as targets for future therapeutic intervention. Though focusing on PD, the strategies we will use are generic and can thus be applied to and lead to progress in other complex diseases.