Human Molecular Genetics Advance Access published online on September 2, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddg302
© 2003 by Oxford University Press
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1 Department of Psychological Medicine, Neuropsychiatric Genetics Unit,
University of Wales College of Medicine, Cardiff, CF14 4XN, UK
* To whom correspondence should be addressed. E-mail: owenmj{at}cf.ac.uk.
The high heritability of schizophrenia has stimulated much work aimed at identifying susceptibility genes using positional genetics. As a result several strong and well-established linkages have emerged. Three of the best-supported regions are 6p24-22, 1q21-22 and 13q32-34 whereby single studies have achieved genome-wide significance at p<0.05 and suggestive positive findings have also been reported in other samples. Other promising regions include 8p21-22, 6q21-25, 22q11-12, 5q21-q33, 10p15-p11 and 1q42. Recently, evidence implicating individual genes within some of the linked regions has been reported and more importantly replicated. Currently, the weight of evidence supports NRG1 and DTNBP1 as schizophrenia susceptibility loci, though work remains before we understand precisely how genetic variation at each locus confers susceptibility and protection. The evidence for COMT, RGS4 and G72 is promising but not yet persuasive. While it is essential that further replications are established, the respective contributions of each gene, relationships with aspects of the phenotype, the possibility of epistatic interactions between genes and functional interactions between the gene products will all need investigation. The ability of positional genetics to implicate novel genes and pathways will open up new vistas for neurobiological research, and all the signs are that now it is poised to deliver crucial insights into the nature of schizophrenia.
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Recent Advances in the Genetics of Schizophrenia
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