title: 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 (α7nAChR), 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 α7nAChR in schizophrenia and show a genetic link between CHRNA7 and startle magnitude, indicating that cholinergic neurotransmission involving the α7nAChR could be involved in sensory registration processes.
authors.affiliation: Department of Clinical Genetics, Applied Human Molecular Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Gl. Landevej 7, 2600, Glostrup, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Bertelsen
authors.affiliation: Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Faculty of Health Sciences, Psychiatric Center Glostrup, University of Copenhagen, Ndr. Ringvej 29-67, 2600, Glostrup, Denmark.
authors.forename: Bob
authors.initials: B
authors.lastname: Oranje
authors.affiliation: Department of Clinical Genetics, Applied Human Molecular Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Gl. Landevej 7, 2600, Glostrup, Denmark.
authors.forename: Linea
authors.initials: L
authors.lastname: Melchior
authors.affiliation: Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Faculty of Health Sciences, Psychiatric Center Glostrup, University of Copenhagen, Ndr. Ringvej 29-67, 2600, Glostrup, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Fagerlund
authors.affiliation: Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen University Hospital, Boserupvej 2, 4000, Roskilde, Denmark.|Institute of Clinical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.|iPSYCH - The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University, Vennelyst Boulevard 4, 8000, Aarhus, Denmark.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Werge
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Jens D
authors.initials: JD
authors.lastname: Mikkelsen
authors.affiliation: Department of Clinical Genetics, Applied Human Molecular Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Gl. Landevej 7, 2600, Glostrup, Denmark. zeynep.tumer@regionh.dk.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Tümer
authors.affiliation: Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Faculty of Health Sciences, Psychiatric Center Glostrup, University of Copenhagen, Ndr. Ringvej 29-67, 2600, Glostrup, Denmark.
authors.forename: Birte Y
authors.initials: BY
authors.lastname: Glenthøj
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003718:Denmark; D005071:Evoked Potentials / Q000235:genetics* / Q000502:physiology; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D065808:Prepulse Inhibition / Q000235:genetics* / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011597:Psychomotor Performance; D012021:Reflex, Abnormal / Q000235:genetics / Q000502:physiology; D013216:Reflex, Startle / Q000235:genetics / Q000502:physiology; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D055815:Young Adult; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics* / Q000502:physiology
chemical_list: C579167:Chrna7 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: Nicotine receptor; P50; PPI; Schizophrenia; Startle magnitude