Abstract:
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To characterize the relationship between protein-coding genes and phenotypes, the International Mouse Phenotyping Consortium (IMPC) is creating an extensive catalogue of mammalian gene function by i) producing knockout mouse lines for the approximately 20,000 protein-coding genes, ii) conducting systemic phenotyping on every knockout line and iii) studying the association between gene-knockout and phenotype. This unique and comprehensive open data set of genome and phenome-wide association opens an unprecedented opportunity to understand the etiology and underlying mechanism of diverse human diseases/traits. As a proof of concept of its utility in human disease studies, here we show that the IMPC gene-to-phenotype association data can be utilized to prioritize candidate genes in genome-wide association studies (GWAS) of psychiatric disorder (e.g., PGC Schizophrenia GWAS). In particular, we identify and prioritize genetic loci/genes associated with sensorimotor gating deficits in schizophrenia by using synthetic gene scores obtained from a meta-analysis combining association across multiple sensory gating phenotypes available in IMPC data (e.g., prepulse inhibition).
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