Figure 1.
Quantile-quantile (QQ) plots for the protein-coding genes with at least one individual with epilepsy or control carrier
Qualifying variants were high-quality, ultra-rare variants with a predicted functional effect but restricting missense variants to REVEL ≥ 0.5 (when defined). We generated p values from the exact two-sided Cochran-Mantel-Haenszel (CMH) test by gene by cluster to indicate a different carrier status of affected individuals in comparison to control individuals. SCN1A (p = 4.4 × 10−8) and NEXMIF (previously known as KIAA2022, p = 8.6 × 10−8) achieved study-wide significance p < 1.6 × 10−7 after Bonferroni correction indicated by dashed line (see gene-based collapsing). (A) Developmental and epileptic encephalopathy (DEE)-affected individuals, (B) genetic generalized epilepsy (GEE)-affected individuals, and (C) non-acquired focal epilepsy (NAFE)-affected individuals. Top ten genes enriched among individuals with epilepsy are labeled. Point coloring determined by CMH odds ratio. Genes labeled in black are known epilepsy genes. Genes labeled in color are candidate epilepsy genes. The green lines represent the 95% confidence interval.