title: Associations between DRDs and schizophrenia in a Korean population: multi-stage association analyses.
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.
authors.affiliation: Department of Psychiatry and Behavioral Science, and Institute of Human Behavioral Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kyu Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Joo
authors.forename: Yong Ick
authors.initials: YI
authors.lastname: Ji
authors.forename: Duk-Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Joo Bae
authors.initials: JB
authors.lastname: Park
authors.forename: In-Won
authors.initials: IW
authors.lastname: Chung
authors.forename: Sang Ick
authors.initials: SI
authors.lastname: Lee
authors.forename: Yeon Ho
authors.initials: YH
authors.lastname: Joo
authors.forename: Yong Min
authors.initials: YM
authors.lastname: Ahn
authors.forename: Joo Yun
authors.initials: JY
authors.lastname: Song
authors.forename: Yong Sik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D056726:Genetic Association Studies; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D011954:Receptors, Dopamine / Q000235:genetics*; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D056910:Republic of Korea; D012559:Schizophrenia / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1