Abstract
Recent large‐scale whole genome sequencing and copy‐number variant (CNV) analysis?with Schizophrenia samples have revealed that rare single‐nucleotide variants (SNVs) and CNV exert significantly larger effects than common single‐nucleotide polymorphisms (SNPs) . Despite large effect size of the CNV, the pathological roles of CNV remains largely unknown, partially because it remains unclear how the functional change of the genes within the regions of the CNVs lead to the pathogenesis of neuropsychiatric disorders. Therefore, in order to discover novel rare SNVs with large effect size and to evaluate the pathogenesis of the discovered mutations, we conducted the sequencing study of the genes involved in neurodevelopment from our CNV analysis with the Japanese SCZ, performed genetic association analysis using a large number of unrelated individuals, and performed in silico and in vitro functional assays of the variants that could have large effects. Through the sequencing study, we found that rare SNV in genes related to neurodevelopment (NDE1, RTN4R) may have functional relevance for the pathophysiology of SCZ. In addition, examining effects of the SNV using novel techniques such as iPS cells may be promising approach in future genetic studies.
