Exp Mol Med.
2011 Jan;43(1):44-52. 10.3858/emm.2011.43.1.005.
Associations between DRDs and schizophrenia in a Korean population: multi-stage association analyses
- Affiliations
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- 1Department of Neuropsychiatry, Eulji University School of Medicine, Eulji General Hospital, Seoul 139-711, Korea.
- 2Center for Genome Research, Samsung Biomedical Research Institute, Seoul 135-710, Korea.
- 3Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
- 4Department of Psychiatry, Dongguk University College of Medicine, Dongguk University International Hospital, Goyang 411-773, Korea.
- 5Department of Neuropsychiatry, School of Medicine, Chungbuk National University, Cheongju 361-711, Korea.
- 6Department of Psychiatry, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Korea.
- 7Department of Psychiatry and Behavioral Science and Institute of Human Behavioral Medicine, Seoul National University College of Medicine, Seoul 110-744, Korea. kys@snu.ac.kr
- KMID: 991622
- DOI: http://doi.org/10.3858/emm.2011.43.1.005
Abstract
- The dysregulation of the dopaminergic system has been implicated in the pathophysiology of major psychosis, including schizophrenia, with dopamine receptor genes (DRDs) presently targeted as the most promising candidate genes. We investigated DRD1-5 for association with schizophrenia using a multi-stage approach in a Korean sample. One hundred forty-two SNPs in DRD1-5 were selected from the dbSNP, and the associations of each SNP were then screened and typed by MALDI-TOF mass spectrometry using pooled DNA samples from 150 patients with major psychosis and 150 controls. Each of the suggested SNPs was then genotyped and tested for an association within the individual samples comprising each pool. Finally, the positively associated SNPs were genotyped in an extended sample of 270 patients with schizophrenia and 350 controls. Among the 142 SNPs, 88 (62%) SNPs in our Korean population were polymorphic. At the pooling stage, 10 SNPs (DRD1: 2, DRD2: 3, and DRD4: 5) were identified (P < 0.05). SNPs rs1799914 of DRD1 (P = 0.046) and rs752306 of DRD4 (P = 0.017) had significantly different allele frequencies in the individually genotyped samples comprising the pool. In the final stage, with the extended sample, the suggestive association of DRD4 with rs752306 was lost, but the association of DRD1 with rs1799914 gained greater significance (P = 0.017). In these large-scale multi-stage analyses, we were able to find a possible association between DRD1 and schizophrenia. These findings suggested the potential contribution of a multi-step strategy for finding genes related to schizophrenia.
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