Assessing the Association between Variants of the ZNF536 Transcription Factor Gene, Family History of Alcoholism, and Severity of Schizophrenia

Abstract The ZNF536 transcription factor gene has been associated with several psychiatric disorders, including schizophrenia, according to genome-wide association studies. Animal models have shown that mutations in ZNF536 are associated with stress and its consequences. The aim of the study is to assess the association between ZNF536 variants (rs2053079(A/G), rs8104557(T/C), rs7259428(T/C), rs7249968(T/C), rs334229(A/G) polymorphic variants and their haplotypes), childhood psychological trauma (alcoholism of a parent), and the severity of schizophrenia assessed by the severity of symptoms. A sample of 663 patients with schizophrenia (426 women and 237 men) was divided into two groups: with a family history of alcoholism (n = 162) and without it (n = 501). An association of two polymorphisms rs2053079 and rs8104557 with the severity of general psychopathological symptoms was found in the group of patients with a family history of alcoholism. In patients carrying the GG (rs2053079(A/G)) and CC (rs8104557(T/C)) genotypes, the severity of symptoms was the highest compared to patients with other genotype–environment combinations. A GCTG haplotype associated with a family history of alcoholism was identified, which contained risk alleles for the rs2053079(A/G), rs8104557(T/C), and rs7259428(T/C) loci. The results expand the understanding of the association of ZNF536 variants with schizophrenia, in particular, indicating the contribution of these variants to the phenotype associated with the severity of schizophrenia in patients with childhood psychological trauma.