We hypothesized that a-synuclein ChIP peaks/pathways common to predicted target genes/pathways from our miRNA analysis, particularly in the top ten pathways, would highlight important genes and pathways implicated in PD pathology. Glycosphingolipid biosynthesis – ganglioseries together with the protein ubiquitination pathway emerged in both the miRNome and the interacton IPA analyses, with three common genes, USP6, NEDD4, and USP3, in the protein ubiquitination pathway. These three genes are also putative targets of three miRNAs over-represented in the miRNomic pathway analysis . Given that the convergence of the miRNomics and the asynuclein interacton approaches highlighted multiple genes in the glycosphingolipid biosynthesis and the protein ubiquitination pathways previously been linked to PD , we further investigated the association of the genes in these pathways with risk for PD. Six independent genome-wide association studies investigated the genomic susceptibility to PD , and we performed a joint analysis of the three datasets to which we had access . The meta-dataset in this study includes 1752 PD cases and 1745 controls. We tested the association of 388 SNPs in 20 genes predicted to be targets of 11 out of the 18 differentially expressed miRNAs belonging to the glycosphingolipid biosynthesis – ganglioseries and the protein ubiquitination pathways . The number of polymorphisms tested in each gene and the markers with positive association findings are summarized in Table 3. GWAS dataset: in the Hussman Institute for Human Genomics dataset , in the National Institute of Neurological Disorders and Stroke dataset , in the Center for Inherited Disease Research dataset . Consistent evidence for association was also found for rs2059198 in ST8SIA4 in the glycosphingolipid biosynthesis pathway . The effect sizes of those SNPs are small, which is expected for PLX4032 customer reviews complex diseases: the median odds ratio for associated SNPs in GWAS is 1.3 . As a result, none of these SNPs would survive the stringent Bonferroni correction for multiple testing given the sample size. The trend for association in several GWAS datasets and in the CT99021 GSK-3 inhibitor meta-analysis, however, supports the possible involvement of these genes in PD etiology.