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Transcription factor 4 as an important determinant of gating function in schizophrenia

Schizophrenia (SZ) is a complex disorder that results from the interplay of genetic and environmental risk factors. It is characterized by the presence of delusions and hallucinations (positive symptoms), apathy and social withdrawal (negative symptoms), and stable impairments in specific domains of cognitive function. Over the past decade, significant progress in understanding SZ has been made by establishing consortia that conduct very large genome-wide association studies (GWASs). The GWAS design provides high-throughput SNP genotyping, following an “agnostic” approach that lacks subjective assumptions concerning gene candidacy. The report by Quednow et al. (1) in PNAS focuses on SZ risk polymorphisms in the transcription factor 4 (TCF4) gene, a locus that has been identified as a significant genetic risk factor for SZ in recent GWASs (2, 3). The authors examined whether any of the TCF4 risk alleles affect sensory gating, as measured by the P50 suppression of the auditory evoked potential. As initially hypothesized, P50 suppression was significantly decreased in carriers of four TCF4 risk alleles.