Table 1.
GWAS datasets.
Figure 1.
X-linked genes associated with autoimmune disease risk.
All genes that showed evidence of association in a gene-based test and replication, including suggestive replication in any other dataset (see main text) are presented for the a) FMS.comb b) FMF.comb c) FM02 and d) sex-differentiated effect size tests (Materials and Methods). X-axis denotes the different datasets, with their names following the notation from Table 1. Y-axis displays the different gene names. For each gene, the more significant p-value of the truncated tail strength and truncated product methods is displayed on a −log10 scale according to the enclosed color scale. A “*” represents the discovery dataset and “**” indicates datasets in which replication is significant after correcting for the number of genes tested for replication. These appear in grey when the discovery and replication are in datasets of the same disease (or across the related Crohn's disease and ulcerative colitis). Numerical values corresponding to this figure are presented in Tables 2–3.
Table 2.
Gene-based associations replicating in similar diseases.
Table 3.
Gene-based associations replicating in other diseases.
Table 4.
Gene set associations.
Figure 2.
X-linked autoimmune disease risk genes are differentially expressed between tissues.
X-axis presents 13 of the associated X-linked genes for which gene expression data was available for analysis. For each, a z-score is presented for the deviation of expression in each of 74 tissues (y-axis) from the average expression of that gene across all tissues (Materials and Methods). For comparison, the last column shows average z-scores across all 504 X-linked genes that were tested as part of the entire XWAS for which expression data was available. Several associated genes exhibit significantly higher expression in immune-related tissues (see main text and Figure 3).
Figure 3.
Three X-linked disease risk genes show high expression in immune-related tissues and cells.
ARHGEF6 (a), IL13RA1 (b), and ITM2A (c) show expression greater than 4 standard deviations above the average expression of these genes in T-cells (highest in CD4+ in purple), CD14+ monocytes (blue), and the thymus (red), respectively. Y-axis follows the respective tissues from Figure 2 and x-axis denotes a z-score for the deviation of expression in each tissue from the average expression of that gene. The title of each panel includes the name of the gene and the tissue with the highest expression for that gene.
Figure 4.
Interactome of X-linked disease risk genes.
All 22 X-linked protein-coding genes that showed evidence of association and replication (Figure 1) are denoted by black diamonds and are presented together with genes that interact with them (grey circles) (Materials and Methods). Physical interactions refer to documented protein-protein interactions. Genetic interactions represent genes where perturbations to one gene affect another. Predicted interactions were obtained from orthology to interactions present in other organisms [159]. All but four of these 22 genes share interacting partners according to these known and predicted interactions. Results of a pathway analysis based on this interactome are presented in Table 5.
Table 5.
Gene-enrichment analysis of the interactome.