Cited by 1,141Schizophrenia research and treatmentNicotinic Acetylcholine Receptors StudyGenetic Associations and Epidemiology

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Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus

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Freedman, Robert, Coon, Hilary, Myles-Worsley, Marina, Orr-Urtreger, Avi, Olincy, Ann, Davis, Ashley, Polymeropoulos, Mihael, Holik, John, Hopkins, Jan, Hoff, Mark, Rosenthal, Judy, Waldo, Merilyne C., Reimherr, Fred, Wender, Paul, Yaw, Jeffrey, Young, David A., Breese, Charles R., Adams, Catherine, Patterson, David, Adler, Lawrence E., Kruglyak, Leonid, Leonard, Sherry, Byerley, William·1997·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.94.2.587PMC PMC19557

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Abstract

Inheritance of a defect in a neuronal mechanism that regulates response to auditory stimuli was studied in nine families with multiple cases of schizophrenia. The defect, a decrease in the normal inhibition of the P50 auditory-evoked response to the second of paired stimuli, is associated with attentional disturbances in schizophrenia. Decreased P50 inhibition occurs not only in most schizophrenics, but also in many of their nonschizophrenic relatives, in a distribution consistent with inherited vulnerability for the illness. Neurobiological investigations in both humans and animal models indicated that decreased function of the α7-nicotinic cholinergic receptor could underlie the physiological defect. In the present study, a genome-wide linkage analysis, assuming autosomal dominant transmission, showed that the defect is linked [maximum logarithm of the odds (lod) score = 5.3 with zero recombination] to a dinucleotide polymorphism at chromosome 15q13-14, the site of the α7-nicotinic receptor. Despite many schizophrenics’ extremely heavy nicotine use, nicotinic receptors were not previously thought to be involved in schizophrenia. The linkage data thus provide unique new evidence that the α7-nicotinic receptor gene may be responsible for the inheritance of a pathophysiological aspect of the illness.

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Authors: Freedman, R., Coon, H., Myles-Worsley, M., Orr-Urtreger, A., Olincy, A., Davis, A., Polymeropoulos, M., Holik, J., Hopkins, J., Hoff, M., Rosenthal, J., Waldo, M. C., Reimherr, F., Wender, P., Yaw, J., Young, D. A., Breese, C. R., Adams, C., Patterson, D., Adler, L. E., Kruglyak, L., Leonard, S., & Byerley, W.
Affiliations: Baylor College of Medicine (US)
Departments of Psychiatry, Pharmacology, Biochemistry, and Preventive Medicine and Biophysics, University of Colorado School of Medicine, Denver Veterans Affairs Medical Center, and Eleanor Roosevelt Institute for Cancer Research, Denver, CO 80262; Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT 84132; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3498; National Center for Human Genome Research/National Institutes of...
ORCID: Freedman, Robert
Coon, Hilary
Polymeropoulos, Mihael
Young, David A.
Breese, Charles R.
Patterson, David
Kruglyak, Leonid
Byerley, William
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1997-01-21
Volume: 94
Issue: 2
Pages: 587-592
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.94.2.587
PMC: PMC19557
OpenAlex: W2144671685
Cited by: 1,141
References: 63
Citations by year: 2026: 3 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 11 · 2020: 16 · 2019: 15 · 2018: 6 · 2017: 14 · 2016: 19 · 2015: 46 · 2014: 25 · 2013: 28 · 2012: 39
FWCI: 62.17
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Veterans Affairs
National Institutes of Health (5k02mh001089-03, 1f32mh010168-01, DA09457)
National Institute on Aging (T32AG000029)
National Institute of Mental Health (MH-44212, P50MH044212, MH01089, MH-10168-F32)
National Institute on Drug Abuse (R01DA009457)
National Center for Research Resources (P41RR003655, M01RR000064)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: schizophrenia, alpha7 nicotinic acetylcholine receptor, genetic linkage, autosomal dominant inheritance, attention deficits, family-based genetic study, nicotine use
MeSH terms: Auditory Perception, Chromosomes, Human, Pair 15, Evoked Potentials, Female, Genes, Genetic Markers, Humans, Genetic Linkage, Male, Pedigree, Receptors, Nicotinic, Schizophrenia, Chromosomes, Artificial, Yeast

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Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus

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