title: Family-based association testing strongly implicates DRD2 as a risk gene for schizophrenia in Han Chinese from Taiwan.
abstract: The gene that codes for dopamine receptor D2 (DRD2 on chromosome 11q23) has long been a prime functional and positional candidate risk gene for schizophrenia. Collectively, prior case-control studies found a reliable effect of the Ser311Cys DRD2 polymorphism (rs1801028) on risk for schizophrenia, but few other polymorphisms in the gene had ever been evaluated and no adequately powered family-based association study has been performed to date. Our objective was to test 21 haplotype-tagging and all three known nonsynonymous single-nucleotide polymorphisms (SNPs) in DRD2 for association with schizophrenia in a family-based study of 2408 Han Chinese, including 1214 affected individuals from 616 families. We did not find a significant effect of rs1801028, but we did find significant evidence for association of schizophrenia with two multi-marker haplotypes spanning blocks of strong linkage disequilibrium (LD) and nine individual SNPs (Ps<0.05). Importantly, two SNPs (rs1079727 and rs2283265) and both multi-marker haplotypes spanning entire LD blocks (including one that contained rs1801028) remained significant after correcting for multiple testing. These results further add to the body of data implicating DRD2 as a schizophrenia risk gene; however, a causal variant(s) in DRD2 remains to be elucidated by further fine mapping of the gene, with particular attention given to the area surrounding the third through fifth exons.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, and Medical Genetics Research Center, SUNY Upstate Medical University, Syracuse, NY 13210, USA. glatts@upstate.edu
authors.forename: S J
authors.initials: SJ
authors.lastname: Glatt
authors.forename: S V
authors.initials: SV
authors.lastname: Faraone
authors.forename: J A
authors.initials: JA
authors.lastname: Lasky-Su
authors.forename: T
authors.initials: T
authors.lastname: Kanazawa
authors.forename: H-G
authors.initials: HG
authors.lastname: Hwu
authors.forename: M T
authors.initials: MT
authors.lastname: Tsuang
mesh_terms: D044466:Asian People / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D003545:Cysteine / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012306:Risk; D012559:Schizophrenia / Q000235:genetics*; D012694:Serine / Q000235:genetics; D013624:Taiwan
chemical_list: D017448:Receptors, Dopamine D2; D012694:Serine; D003545:Cysteine