Fig 1.
A Manhattan plot of the TWAS results for UF.
Each dot corresponds to the gene of which predicted expression is associated with UF. The X-axis denotes the chromosome numbers of the genes and the Y-axis denotes −log10(TWAS P-values). The yellow line indicates a Bonferroni significant threshold (P < 1.90 × 10−6). Nine significant TWAS genes are represented as red dots with gene labels.
Table 1.
A list of significant TWAS genes associated with UF (P < 1.90 × 10−6).
Fig 2.
Regional association plots showing conditional and joint analyses results.
(A) The regional association plot of chromosome 11. (B) The regional association plot of chromosome 12. (C) The regional association plot of chromosome 13. The middle part of each figure represents all genes located in the region. The green bars indicate jointly significant genes that are responsible for most GWAS signals in the region, the yellow bars represent TWAS genes that are no longer significant after accounting for conditionally independent genes, and the gray bars indicate genes that were neither jointly significant nor marginally significant in that region. The colored dots next to the jointly or marginally significant genes indicate tissue panels where the genes were detected, as summarized in Table 1. The lowest part of each panel is a Manhattan plot of the GWAS signals. Black dots represent the GWAS P-values of SNPs before conditioning tests, and blue dots represent the GWAS P-value of SNPs after removing the effects of jointly significant genes.
Fig 3.
Functional annotation networks consisting of biological pathways enriched with TWAS genes for UF.
(A) Four major clusters grouped into three parental biological pathways were enriched with positively associated TWAS genes (TWAS P-value < 0.05 and Z-score > 0). (B) Four major clusters of biological pathways were enriched with negatively associated TWAS genes (TWAS P-value < 0.05 and Z-score < 0). The major clusters are the sub-networks in the top 25% for connectivity score as calculated by the MCODE in each functional annotation network. Each node represented by a pie chart indicates an enriched biological pathway, and the sector size is proportional to the number of genes that originate from each tissue panel. The node size corresponds to the number of panels where TWAS genes were enriched.
Table 2.
A list of five toxic chemicals discovered based on CTD as potentially toxic chemicals for UF.