‘Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia‘ has been published in iScience.
In this study, we performed interaction proteomics for 6 schizophrenia risk genes prioritized from GWAS loci in human induced excitatory neurons. The resulting protein-protein interaction network is enriched for common variant risk of schizophrenia across both European and East Asian ancestries and can complement fine-mapping and eQTL data to prioritize genes in GWAS loci. We observed convergent genetic signals in the HCN1 sub-network, which is enriched for common variant risk of schizophrenia and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings in this study (and the sister study on autism spectrum disorders) showcase brain cell-type-specific protein interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in neuropsychiatric disorders.
