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. 2021 Dec 13;118(51):e2112560118. doi: 10.1073/pnas.2112560118

Fig. 4.

Fig. 4.

Overall burden of rare variants in severe, extremely treatment-resistant schizophrenia compared to typical schizophrenia and control individuals. (A) No difference observed between severe, extremely treatment-resistant schizophrenia, typical schizophrenia, and controls for benign missense variants in missense intolerant genes (Mis Z > 3.09, n = 956 genes). (B) Increased burden of damaging missense MTR variants in severe, extremely treatment-resistant schizophrenia compared to typical schizophrenia in missense intolerant genes (Mis Z > 3.09, n = 956 genes). (C) Increased burden of loss-of-function variants in severe, extremely treatment-resistant schizophrenia compared to typical schizophrenia in loss-of-function (LoF) intolerant genes (pLI > 0.9, n = 3,063). (D) Increased burden of damaging missense MTR variants in severe, extremely treatment-resistant schizophrenia compared to typical schizophrenia in missense intolerant schizophrenia exome meta-analysis (SCHEMA) genes (n = 45 genes). (E) Nonsignificant increase in burden of loss-of-function variants in severe, extremely treatment-resistant schizophrenia compared to typical schizophrenia in loss-of-function intolerant SCHEMA genes (n = 75 genes). (F) Increased burden of damaging missense MTR and loss-of-function in severe, extremely treatment-resistant schizophrenia compared to typical schizophrenia in intolerant SCHEMA genes (n = 45 for missense intolerant and n = 75 for loss-of-function intolerant SCHEMA genes). Odds ratios (OR) and P values shown are based on a comparison of typical schizophrenia individuals to controls and severe, extremely treatment-resistant schizophrenia individuals to typical schizophrenia using one-sided Cochran–Mantel–Haenszel test. Benign missense: missense variants with REVEL score < 0.15, Missense damaging MTR: missense variants with REVEL score > 0.5 and missense tolerance ratio false discovery rate < 0.1. SCZ: schizophrenia, SETRS: severe, extremely treatment-resistant schizophrenia.