Case-control and family-based association studies between the neuregulin 1 (Arg38Gln) polymorphism and schizophrenia

Genetic variations in the neuregulin 1 (NRG1), a critical gene in neuronal development, have been reported to be associated with schizophrenia in several reports. Association has been reported between a non-synonymous NRG1 polymorphism (Arg38Gln) and schizophrenia in a Chinese family-based association study; however, this finding is not yet confirmed by other research findings analyzed using independent sample. To replicate this finding and assess the association between age at onset of schizophrenia and the NRG1 Arg38Gln polymorphism, we investigated the prevalence of this polymorphism in a Chinese population (228 schizophrenic disorder patients and 269 controls). We were unable, however, to demonstrate a significant association between the NRG1 Arg38Gln polymorphism and schizophrenia (P = 0.869 for genotype and P = 0.597 for allelic frequencies) or age at onset (P = 0.940). Our family-based association study (15 schizophrenic bios and 221 schizophrenic trios) demonstrated 38Gln was transmitted in excess by the parent to the affected offspring (P = 0.052). However, this result contrasts with a previous finding in Chinese that 38Arg was transmitted in excess by the parent to the affected offspring. On the basis of the contrast between the findings of other study and our family-based study and the negative findings of our case-control association study, we conclude that NRG1 Arg38Gln polymorphism is not likely to play a major role in the pathogenesis of schizophrenia in Chinese populations.