Fig. 2

Relative enrichment of GEM-damaging variants in epilepsy and Cardiomyopathy/Arrhythmia (CMAR) genes. The SDY cohort has enriched GEM-damaging (A) epilepsy and (B) cardiac gene burden compared to a sex- and ancestry-matched control cohort. Histograms (gray bars) represent distributions of GEM-damaged genes (GEM Score ≥ 0.69) sampled randomly from RefSeq genes using a root phenotype from the SDY cohort (n = 211) (bottom panels) and 1000 Genomes Project Cohort (control) matched for sex and ancestry (n = 211) (top panels). GEM-damaged genes identified in the Epilepsy (n = 191 genes, green) (A) and CMAR1 (n = 118 genes, orange) (B) gene lists were significantly different between the SDY and control cohorts (dark arrows, epilepsy, p = 0.027; cardiac p < 0.001). Light arrows represent the number of GEM-damaged genes identified in a control housekeeping gene set. (C) The results in Fig. 2A and B and Additional File 1: Figure S2 were Z-score transformed to make the gene list findings comparable. The plot reveals a considerable enrichment in both cardiac and epilepsy gene lists (+ 8.0 to + 13.0 SDs). Black line represents the expected normal distribution