Genetic Effects and on Visual Learning of Patients with Schizophrenia.

Visual learning plays an important role in general populations and patients with schizophrenia. Genetic influences on visual learning remain unknown. Two functional single nucleotide polymorphisms (SNPs), Ser704Cys of the gene and M24 (rs1421292) of the gene, are strongly associated with pathogenesis and pathophysiology of schizophrenia. This study examined these two SNPs' effects on visual learning in schizophrenia patients. Two hundred seventy-one patients (mean age, 37.0 years [SD = 9.3]; 159 men) with chronic schizophrenia were genotyped for the Ser704Cys and M24 SNPs and assessed for visual learning with Visual Reproduction II (delayed reproduction) of Wechsler Memory Scale - III (WMS-III). For comparison, verbal learning (using Word list II of WMS-III) and attention (by Continuous Performance Test) were also measured. The Ser carriers excelled Cys/Cys homozygotes in visual learning (p=0.004, effect size: 0.43), but not in other cognitive functions. M24 A-allele carriers and M24 T/T homozygotes performed similarly (effect size: 0.07). In SNP-SNP interaction analysis, the patients with Ser carrier_T/T had better visual learning than those with Cys/Cys_T/T (p=0.004, effect size: 0.70) and those with Cys/Cys_A-allele carrier (p=0.003, effect size: 0.65). Education had a positive effect (p=0.007), while negative symptoms had a negative effect (p<0.001) on visual learning. The findings suggest that genetic variations in Ser704Cys and M24 affect visual learning in schizophrenia patients. The effect sizes of SNP-SNP interaction surpassed the sum (0.50) of effect sizes from two individual genes, suggesting synergistic interaction.