To assess the degree to which changes in gene expression or splicing might be associated with PD case or control status, we performed a TWAS or methylation-wide association study (MWAS) using the method by Gusev et al.12 Expression reference weights were obtained from the CommonMind Consortium dorsolateral prefrontal cortex RNA-seq and RNA-seq splicing data sets, which are based on 467 samples (209 individuals with schizophrenia, 206 controls, and 52 individuals with affective disorder), and methylation data from our PD brain methylation data set.19 For all genes (or isoforms for splicing analysis), TWAS and MWAS P values were obtained, and all genes and isoforms passing multiple testing correction at the FDR 0.05 level, genome-wide, were considered significant. Where multiple genes were implicated within a region, we performed further conditional analyses using Fusion12 to identify whether there were single or joint TWAS and MWAS signals at each locus. Conditional analyses were performed independently across gene expression and methylation data sets.
