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Background

While rare deleterious exonic variants are thought to contribute to risk for schizophrenia, identification of specific genes and pathways has proven challenging. Founder populations, such as the Ashkenazi Jewish (AJ) population, are enriched for rare variation, providing enhanced power.

Methods

High-depth (> 30x) Illumina whole genome sequencing was performed; we restricted analysis to the exome. After strict QC, data were available from 786 AJ cases and 463 AJ controls. All variants observed even once in gnomAD (non-neuro) and TOPMED databases (total N> 158K) were filtered, resulting in 12,011 novel loss of function and missense (LoFM) autosomal variants, which were then grouped by gene.

Results

A total of 731 genes were hit by novel LoFM variants in 2 or more cases and 0 controls; 144 genes were hit by novel LoFM variants in 2 or more controls and 0 cases (p< e-7 by permutation …