The significance of the association between a dataset and a canonical pathway was determined by comparing the HSC number of genes in a dataset that participate in a given pathway to the total number of occurrences of these genes in all pathway annotations that are stored in the IPAKB. A Fisher��s exact test was used to calculate the p-value to determine the probability that the association between the genes in the dataset and the canonical pathway is explained only by chance. The level of statistical significance was set to p,0.05. Each pathway analysis generated the top canonical pathways with a statistical significance . A joint association analysis was Fingolimod Src-bcr-Abl inhibitor performed on three PD GWAS datasets: The HIHG at the University of Miami , the NINDS , and the joint dataset from the Progeni/GenePD studies that was genotyped at the CIDR . This meta-dataset has a combined sample size of 1752 cases and 1745 controls. Details regarding the characteristics of the study participants and the markers analyzed in each dataset are described in detail in the original reports . Briefly, genotype and phenotype data from the NINDS and Progeni/GenePD studies were downloaded from dbGAP . HIHG genotype data were generated using the Illumina Infinium 610-quad BeadChip. Imputation of SNP genotypes from the three GWAS dataset was performed using the software package Impute . Samples with a genotyping efficiency ,0.98 and SNPs with a genotyping call rate ,0.98 were removed from the analysis. In addition, SNPs with a minor allele frequency ,0.01 or a Hardy-Weinberg equilibrium p-value,1027 were excluded. Population stratification was evaluated using Eigenstrat . Cochran-Armitage trend tests were used to assess allelic association at each SNP using PLINK . These analyses were carried out using the Ingenuity Pathway Analysis software and each plot displays the pathways ranked by significance level on the y-axis. The x-axis on the top is for the negative logarithm of the pvalue . The significance of the association between a dataset and a canonical pathway was determined by comparing the number of genes in a dataset that participate in a given pathway to the total number of occurrences of these genes in all pathway annotations that are stored in the Ingenuity Knowledge Base.