Figure 2.

Gene set enrichment analysis shows indviduals with mild epilepsies enriched for rare variants in genes associated with severe epilepsies

Gene set burden testing with 24 genes drawn from the 43 OMIM epileptic encephalopathy phenotype series with dominant transmission by limiting to genes harboring damaging (REVEL ≥ 0.5) missense variants in all three epilepsies (see gene set enrichment testing, Table S5). All variants are ultra-rare (see subjects and methods). Pooled odds ratio, 95% confidence intervals, and FDR-corrected p value were generated from the exact two-sided Cochran-Mantel-Haenszel (CMH) test. Odds ratio and FDR-adjusted p values displayed for comparisons with unadjusted p value < 0.05. x axis displays the log₁₀ of the odds ratio and confidence intervals. PTV, protein-truncating variants; “damaging,” REVEL ≥ 0.5 (when defined); “intolerant,” MTR ≤ 0.78 (when defined); DEE, developmental and epileptic encephalopathy; GGE, genetic generalized epilepsy; NAFE, non-acquired focal epilepsy.