Background: Variation at the dysbindin gene (DTNBP1) has been associated with increased risk for schizophrenia in numerous independent samples and recently with deficits in general and domain-specific cognitive processing. The relationship between dysbindin risk variants and sensory-level deficits in schizophrenia remains to be explored. We investigated P1 performance, a component of early visual processing on which both patients and their relatives show deficits, in carriers and noncarriers of a known dysbindin risk haplotype. Methods: Event-related potential responses to simple visual isolated-check stimuli were measured using high-density electrical scalp recordings in 26 individuals meeting DSM-IV criteria for schizophrenia, comprising 14 patients who were carriers of the dysbindin risk haplotype and 12 patients who were nonrisk haplotype carriers. Results: Carriers of the dysbindin risk haplotype demonstrated significantly reduced P1 amplitudes compared with noncarriers. A large effect size of d = .89 was calculated for the difference in P1 amplitude over scalp sites where the deficit was maximal. Conclusions: The P1 deficits associated with a dysbindin risk haplotype previously identified in our sample presents functional confirmation of its deleterious effect on brain activity. Building on evidence of dysbindin’s role in higher cognitive function, these early visual processing deficits suggest a generalized role for dysbindin in brain function and is likely to be part of the mechanism by which illness susceptibility is mediated. ; PUBLISHED ; PMID: 17945199