Extended Data Fig. 5: Results from burden analysis of protein-truncating and damaging missense URVs combined.
a, Joint burden of protein-truncating and damaging missense URVs at the individual-gene level. The observed −log10-transformed P values are plotted against the expectation given a uniform distribution. Burden analyses are performed across four epilepsy groups – 1,938 DEEs, 5,499 GGE, 9,219 NAFE, and 20,979 epilepsy-affected individuals combined – versus 33,444 controls. P values are computed using a Firth logistic regression model testing the association between the case-control status and the number of URVs (two-sided); the red dashed line indicates exome-wide significance P = 3.4 × 10−7 after Bonferroni correction (see Methods). b, Comparison of the joint burden in a with the burden of protein-truncating URVs. The odds ratio (OR) of protein-truncating plus damaging missense URVs (y-axis) and that of protein-truncating URVs alone (x-axis) are compared. Each dot represents a gene with nominally significant enrichment (OR > 0 and P ≤0.05) of either protein-truncating URVs or the two variant classes combined.
