Psychiatric disorders such as schizophrenia and major depressive disorder (MDD) are likely to be caused by multiple susceptibility genes, each with small effects in increasing the risk of illness. Identifying DNA variants associated with schizophrenia and MDD is a crucial step in understanding the pathophysiology of these disorders.

To investigate whether the SP4 gene plays a significant role in schizophrenia or MDD in the Han Chinese population.

We focused on nine single nucleotide polymorphisms (SNPs) harbouring the SP4 gene and carried out case–control studies in 1235 patients with schizophrenia, 1045 patients with MDD and 1235 healthy controls recruited from the Han Chinese population.

We found that rs40245 was significantly associated with schizophrenia in both allele and genotype distributions (Pallele = 0.0005, Pallele = 0.004 after Bonferroni correction; Pgenotype = 0.0023, Pgenotype = 0.0184 after Bonferroni correction). The rs6461563 SNP was significantly associated with schizophrenia in the allele distributions (Pallele = 0.0033, Pallele = 0.0264 after Bonferroni correction).

Our results suggest that common risk factors in the SP4 gene are associated with schizophrenia, although not with MDD, in the Han Chinese population.