Fig. 2.

The burden of rare variants in missense and loss-of-function intolerant genes in 112 individuals with severe, extremely treatment-resistant schizophrenia and 4,929 healthy controls. (A) Missense intolerant genes were those with missense Z > 3.09 and (B) loss-of-function intolerant genes were those with probability of being loss-of-function intolerant (pLI) score > 0.9 as per gnomAD. Unadjusted two-sided Cochran–Mantel–Haenszel exact P values, effect sizes between severe, extremely treatment-resistant schizophrenia and healthy controls represented as odds ratios, and horizontal bars indicating 95% confidence intervals are shown. LoF: Loss-of-Function variants, Miss Dmg Missense Tolerance Ratio (MTR): Damaging missense variants with REVEL score > 0.5 and missense tolerance ratio false discovery rate < 0.1, Miss Dmg: Damaging missense variants with REVEL score > 0.5, Miss Ben: Benign missense variants with REVEL score < 0.15, Syn: Synonymous variants. *False discovery rate < 0.1.