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Background  Recent genome-wide association study showed rs10940346 locus near  EMB  gene was significantly associated with schizophrenia and suggested that  EMB  gene is one of the potentially causal genes for schizophrenia, but no causal variant has been identified. Our study aims to further verify  EMB  gene is a susceptibility gene for schizophrenia and to identify potentially causal variants in  EMB  gene that lead to schizophrenia.    Methods  Targeted sequencing for the un-translated region and all exons of  EMB  gene was performed among 1803 patients with schizophrenia and 997 healthy controls recruited from Chinese Han population.    Results  A total of 58 high-quality variants were identified in case and control groups. Seven of them are nonsynonymous rare variations,  EMB : p.(Ala52Thr), p.(Glu66Gly), p.(Ser93Cys), p.(Ala118Val), p.(Ile131Met), p.(Gly163Arg) and p.(Arg238Tyr), but none of them reached statistical significance. Among them, p.(Ile131Met), p.(Gly163Arg) and p.(Arg238Tyr), were predicted to be deleterious variants. In addition, a common variant, rs3933097 located in 3′-UTR of  EMB  gene, achieved allelic and genotypic significance with schizophrenia ( P   allele   = 3.82 × 10 − 6 ,  P   genotype   = 3.18 × 10 − 5 ).    Conclusions  Our research first presented a comprehensive mutation spectrum of exons and un-translated region in  EMB  gene for schizophrenia and provided additional evidence of  EMB  gene being a susceptibility gene for schizophrenia. However, further functional validations are necessary to reveal its role in the etiology of schizophrenia.

Rare and common variants analysis of the EMB gene in patients with schizophrenia