Fig 1.
Primary PheWAS results: Variant level findings are displayed in panel (a) The red line represents the level of significance after Bonferroni correction (p<2.7x10-07). The color indicates variant in each gene and the shape indicates each phenotype (ex: variants in PTPN11 are represented in blue, and the association with diastolic blood pressure indicated with the sign +). Correlation plot of association between phenotypes and the subset of independent variants within each gene is displayed in panel (b). The points represent the z-score and the color represent the direction of the association. The color varies from purple (inverse association) to red (positive association). The size of the point corresponds to the p-value (-log10(p)); the stars indicate variants associated with multiple phenotypes.
Table 1.
Table of association between the top SNPs with multiple phenotypes in each gene and significant (p-value < 2.7x10-07) or suggestive (p-value < 1x10-04) associations with HPO phenotypes (A1 corresponds to the effect allele).
Fig 2.
Primary PheWAS results at a gene level.
Plot of PheWAS results for all genes and phenotypes (a). The red line represents the level of significance after FDR correction. Genes are represented by color and phenotypes are indicated by shape. Correlation plot for the set of significant gene–phenotype pairs. (b). The color represents the p-value of association and varies from none associated (grey-white) to significant association (red-dark red).
Table 2.
Table of association between sets of associated phenotype–gene pairs after FDR correction (gene level association performed using SKAT test with variants weighted by their CADD score).
Fig 3.
PheWAS result and linkage plot for variants with pleiotropy in FBN1.
Associations between variants associate with multiple phenotypes (a) and linkage between the variants in FBN1 (b). The red line represents the level of significance after Bonferroni correction (p = 2.7x10-07).
Fig 4.
PheWAS result and linkage plot for variants with pleiotropy in RAS-opathy genes.
Associations between variants with pleiotropic effects in MAP2K1, PTPN11, SOS2 and RASA2, and HPO terms (a) and linkage between the variants (b). The red line represents the level of significance after Bonferroni correction (p = 2.7x10-07).
Table 3.
Table summarizing number of genes, SNPs and phenotypes (HPO terms) for each syndrome included in our analysis.