Association Study of CHRNA7 Promoter Variants with Sensory and Sensorimotor Gating in Schizophrenia Patients and Healthy Controls: A Danish Case–Control Study

Abstract

Schizophrenia is a severe psychiatric disorder with a core component of impaired cognitive function still remaining as one of the greatest challenges in the pharmacological treatment of the disorder. The CHRNA7 gene, encoding the subunit of the human α7 nicotinic acetylcholine receptor (α<inf>7</inf>nAChR), is suggested as a susceptibility factor for schizophrenia. CHRNA7 has also been genetically linked to the P50 auditory evoked potential deficit, a candidate endophenotype of schizophrenia, but not to prepulse inhibition of the startle reflex (PPI). In this study, 95 antipsychotic-naïve schizophrenic patients and 450 unaffected controls were screened for CHRNA7 promoter variants to investigate the association with schizophrenia, P50 suppression and PPI. We found that the promoter variant -194C (rs28531779) was significantly associated with schizophrenia, but did not find any association of this variant with P50 suppression or PPI. In addition, individuals with CHRNA7 promoter variants had elevated startle magnitude in pulse-alone trials compared to individuals without a variant. The present findings provide further support for a role of the α<inf>7</inf>nAChR in schizophrenia and show a genetic link between CHRNA7 and startle magnitude, indicating that cholinergic neurotransmission involving the α<inf>7</inf>nAChR could be involved in sensory registration processes.