Associations between DRDs and schizophrenia in a Korean population: multi-stage association analyses.
10.3858/emm.2011.43.1.005
- Author:
Kyu Young LEE
1
;
Eun Jeong JOO
;
Yong Ick JI
;
Duk Hwan KIM
;
Joobae PARK
;
In Won CHUNG
;
Sang Ick LEE
;
Yeon Ho JOO
;
Yong Min AHN
;
Joo Yun SONG
;
Yong Sik KIM
Author Information
1. Department of Neuropsychiatry, Eulji University School of Medicine, Eulji General Hospital, Seoul 139-711, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Asian continental ancestry group;
gene pool;
genetic association studies;
receptors, dopamine;
schizophrenia
- MeSH:
*Genetic Association Studies;
Humans;
Linkage Disequilibrium;
*Polymorphism, Single Nucleotide;
Receptors, Dopamine/*genetics;
Receptors, Dopamine D1/*genetics;
Republic of Korea;
Schizophrenia/*genetics;
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- From:Experimental & Molecular Medicine
2011;43(1):44-52
- CountryRepublic of Korea
- Language:English
-
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.
