Fig. 2

Pinpoint disease-relevant genes and cell types. a Samples collected from unaffected controls and patients are analyzed through genome-wide association studies (GWAS). Genetic variants determination and network analysis reveals genetic candidates. b To validate candidates’ effects, genome editing is carried out in disease-relevant cell types with isogenic background, as vulnerable and resilient population of neurons and glial cells. c Phenotypes are characterized and compared, in order to link functional consequences to specific genes and cell types. OMICs techniques allow to link candidate editing to a differential expression set of genes, overall generating additional candidates. Comparisons among different cell types elucidate genes responsible for cell-type-specific response and cell population vulnerability. Convergent phenotypes of differential genes pinpoint to pathology-relevant pathways. Multiple gene perturbations are useful to detect phenotype modifiers, that can either alleviate, therefore be considered potential therapeutic targets, as well as aggravate phenotypes