Recent advances in the genetics of schizophrenia |
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Authors: | DM Waterworth AS Bassett LM Brzustowicz |
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Institution: | (1) Department of Genetics, Rutgers University, Nelson Biological Laboratories, B336A, 604 Allison Road, Piscataway, New Jersey 08854-8082 (USA), Fax +1 732 445 1147, e-mail: Waterworth@biology.rutgers.edu, US;(2) Department of Psychiatry, University of Toronto, and Genetics Section, Schizophrenia Research Program, Queen Street Division, Centre for Addiction and Mental Health, Toronto, Ontario (Canada), CA;(3) Departments of Psychiatry, University of Medicine, and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey (USA) and Robert Wood Johnson Medical School, Piscataway, New Jersey (USA), US |
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Abstract: | The genetic etiology of schizophrenia, a common and debilitating psychiatric disorder, is supported by a wealth of data.
Review of the current findings suggests that considerable progress has been made in recent years, with a number of chromosomal
regions consistently implicated by linkage analysis. Three groups have shown linkage to 1q21-22 using similar models, with
HLOD scores of 6.5, 3.2, and 2.4. Other replicated loci include 13q32 that has been implicated by two independent groups with
significant HLOD scores (4.42) or NPL values (4.18), and 5p14.1-13.1, 5q21-33, 8p21-22, and 10p11-15, each of which have been
reported as suggestive by at least three separate groups. Different studies have also replicated evidence for a modest number
of candidate genes that were not ascertained through linkage. Of these, the greatest support exists for the DRD3 (3q13.3),
HTR2A (13q14.2), and CHRNA7 (15q13-q14) genes. The refinement of phenotypes, the use of endophenotypes, reduction of heterogeneity,
and extensive genetic mapping have all contributed to this progress. The rapid expansion of information from the human genome
project will likely further accelerate this progress and assist in the discovery of susceptibility genes for schizophrenia.
A greater understanding of disease mechanisms and the application of pharmacogenetics should also lead to improvements in
therapeutic interventions.
Received 11 May 2001; received after revision: 20 July 2001; accepted 18 September 2001 |
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Keywords: | , Linkage, association, epidemiology, endophenotype, PANSS, |
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