Conversion of Gene Expression and GWAS Pathways.
For gene expression analysis, differentially expressed genes between adjacent tissues affected in PD were identified in each individual and adjusted using average control expression profiles. Three subtractions were used to identify genes of interest in PD. The first subtraction between two adjacent tissues relates to a given PD patient (eg CASE N). The second subtraction is in controls, where a similar subtraction as above is performed, and then averaged over the four controls for the two given adjacent tissues. This is denoted as CONTROLAVG. To establish if gene X is of interest in PD between two adjacent tissues, the CONTROLAVG was subtracted from the first subtraction for each patient. An overview of the GWAS PD study is shown. Pathway analysis was performed on each of the GWAS and gene expression PD gene sets derived. Two types of convergence were performed. First, significantly over represented pathways common in both studies were identified (Figure 1). Second, a meta-analysis was carried out to combine the results obtained from the gene expression and the GWAS PD pathway analyses (Table 2). DMV = dorsal motor nucleus, LCER = locus ceruleus, SNGRA = substantia nigra, PTMN = putamen, INSLA = insula.