Neuregulin 3 Genetic Variations and Susceptibility to Schizophrenia in a Chinese Population

The study investigated the possible association of NRG3 gene and schizophrenia in a Han Chinese population. Of a total of 1345, 270 unrelated schizophrenia inpatients, 235 normal control subjects, and 280 nuclear families (trios) with schizophrenia probands were studied. Nine single nucleotide polymorphisms (SNPs) spanning intron 1 to exon 9 of the NRG3 gene were analyzed, starting with the case-control samples. The SNPs showing significant association with schizophrenia in the case-control samples were subsequently studied in the independent trio samples with family-based association analysis. In case-control samples, two SNPs (rs1937970 and rs677221) showed significant genotypic and allelic association with schizophrenia (all p <.05) with rs677221-C being the risk allele for schizophrenia (uncorrected p =.001, odds ratio = 1.439, 95% confidence interval = 1.115–1.858). Haplotypes GC constructed by the two SNPs was also significantly associated with schizophrenia (permutation p value =.0047). In the independent trio samples, rs1937970-A and rs677221-G consistently showed significant under-transmission to schizophrenic offspring (unadjusted p =.003 and p =.004, respectively). In the haplotype–transmission disequilibrium test (TDT) for allelic combination of rs1937970-rs677221, significant under-transmission for haplotype AG (uncorrected p =.006) and over-transmission for haplotype GC (uncorrected p =.004) to the affected schizophrenia offspring were observed. The result supports that the NRG3 gene is a susceptibility gene for schizophrenia.