Fig. 1: Schematic representation of the identified contributions of rare high-impact variants with potential clinical implications to schizophrenia.

The overall “doughnut” graph indicates the study design that included 26 individuals (Supplementary Table S2) with pathogenic/likely pathogenic rare copy number variants (CNVs; blue sections, including five with other reported genetic risk factors indicated by blue checkered overlay). Red sections indicate the total 17 individuals identified to have other types of rare high-impact variants proposed to have potential clinical relevance for schizophrenia; 14 of these, representing 6% of individuals without pathogenic CNVs, are also shown with detailed breakdown of variant types in a bar graph on the right. This shows nine individuals with rare SNVs/indels, and three with CTG tandem repeat expansions (TREs), deemed to have potential clinical implications; also shown are two individuals with ultra-rare LoF variants in ZMYM2, proposed here as a putative schizophrenia-candidate gene. One other individual with an ultra-rare LoF variant in ZMYM2, and two individuals with clinically relevant rare SNVs/indels (Tables 1, 3), also had a pathogenic CNV (blue checkered overlay on red section of doughnut graph). Also shown (yellow sections) are 16 individuals belonging to the top twentieth percentile of schizophrenia-PRS (Supplementary Fig. S7); note that schizophrenia-PRS has not yet reached proposed clinical relevance.