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Schizophrenia Bulletin Advance Access published online on July 14, 2007
Schizophrenia Bulletin, doi:10.1093/schbul/sbm076
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© The Author 2007. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Dopamine Genes and Schizophrenia: Case Closed or Evidence Pending?

Michael E. Talkowski3, Mikhil Bamne2, Hader Mansour2 and Vishwajit L. Nimgaonkar1,2
2 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine and Graduate School of Public Health, Room 441, 3811 O'Hara Street, Pittsburgh, PA 15213
3 Department of Human Genetics, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, PA

1 To whom correspondence should be addressed; tel: 412-246-6353, fax: 412-246-6350, e-mail: nimga+{at}pitt.edu.

The dopamine hypothesis of schizophrenia (SZ) has motivated a large number of genetic association studies but few if any dopaminergic (DA) polymorphisms are accepted as credible risk factors at present. To evaluate whether dopamine-related genes have been investigated adequately, we surveyed public genetic databases and published SZ association studies with regard to 14 conventional DA genes and 7 selected dopamine-interacting proteins. We estimate that 325 polymorphisms would be required to evaluate the impact of common variation on SZ risk among Caucasian samples. To date, 98 polymorphisms have been analyzed in published association studies. We estimate that only 19 of these variations have been evaluated in samples with at least 50% power to detect an association of the effect size commonly found in genetically complex disorders. While it is possible that DA genes do not harbor genetic risk factors for SZ, our review suggests that satisfactory conclusions for most genes cannot be drawn at present. Whole-genome association studies have begun to fill this void, but additional analyses are likely to be needed. Recommendations for future association studies include analysis of adequately powered samples, judiciously selected polymorphisms, multiple ethnic groups, and concurrent evaluation of function at associated single-nucleotide polymorphisms.

Keywords: genetic association / schizophrenia / dopamine / meta-analysis


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 Hum Mol GenetHome page
M. E. Talkowski, G. Kirov, M. Bamne, L. Georgieva, G. Torres, H. Mansour, K. V. Chowdari, V. Milanova, J. Wood, L. McClain, et al.
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