A meta-analysis and transmission disequilibrium study of association between the dopamine D3 receptor gene and schizophrenia

Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259, Spurlock, G., Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, Mant, R., Murphy, K., Jones, L., Cardno, A., Asherson, P., Blackwood, D., Muir, W., Meszaros, K., Aschauer, H., Mallet, J., Laurent, C., Pekkarinen, P., Seppala, J., Stefanis, C. N., Papadimitriou, G. N., Macciardi, F., Verga, M., Pato, C., Azevedo, H., Crocq, M. A., Gurling, H. and Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 1998. A meta-analysis and transmission disequilibrium study of association between the dopamine D3 receptor gene and schizophrenia. Molecular Psychiatry 3 (2) , pp. 141-149.

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Abstract

We performed a meta-analysis of over 30 case-control studies of association between schizophrenia and a bi-allelic, Bali polymorphism in exon 1 of the dopamine D3 receptor gene. We observed a significant excess of both forms of homozygote in patients (P = 0.0009, odds ratio (OR) = 1.21, 95% Confidence Interval (CI) = 1.07-1.35) in the combined sample of 5351 individuals. No significant heterogeneity was detected between samples and the effects did not appear to be the product of publishing bias. In addition we undertook an independent, family-based association study of this polymorphism in 57 parent/proband trios, taken from unrelated European multiplex families segregating schizophrenia. A transmission disequilibrium test (TDT) showed a significant excess of homozygotes in schizophrenic patients (P = 0.004, odds ratio (OR) = 2.7, 95% CI = 1.35-5.86). Although no significant allelic association was observed, a significant association was detected with the 1-1 genotype alone (P = 0.02, OR = 2.32, 95% CI = 1.13-4.99). In addition when the results of the family-based association study were included in the meta-analysis, the homozygosity effect increased in significance (P = 0.0002, OR = 1.23, 95% CI = 1.09-1.38). The results of the meta-analysis and family-based association study provide independent support for a relationship between schizophrenia and homozygosity at the Bali polymorphism of the D3 receptor gene, or between a locus in linkage disequilibrium with it.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	Nature Publishing Group
ISSN:	1359-4184
Last Modified:	31 Oct 2022 09:36
URI:	https://orca.cardiff.ac.uk/id/eprint/81730

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