Fig. 1: Study analytical design.
From: A proteogenomic view of Parkinson’s disease causality and heterogeneity
1103 subjects were analyzed with SomaScan for 4135 unique proteins in CSF. The comparison between GBA + PD patients and GBA + unaffected controls (UC) retrieved six differentially expressed (DE) proteins. The comparison between LRRK2 + PD patients and LRRK2 + UC retrieved seven DE proteins. The comparison between idiopathic PD patients and HC non-mutation carriers retrieved 23 DE proteins. Patients and controls were also combined and compared, which retrieved 122 DE proteins. Idiopathic PD patients were further analyzed, and two endotypes were identified based on CSF proteomics. 1264 subjects were sequenced genome wide to detect a total of 9743041 SNPs. For the 804 patients that had both genomic and proteomic data, a pQTL analysis was performed that identified 744 unique proteins with a significant cis-pQTL. The pQTLs combined with a meta GWAS for PD performed by Nalls et al.70, led to the proposal of 68 unique CSF proteins presumed to be causal for PD.
