Family-based association testing strongly implicates DRD2 as a risk gene for schizophrenia in Han Chinese from Taiwan
Resource
Molecular Psychiatry.
Journal
Molecular Psychiatry
Journal Volume
14
Journal Issue
9
Pages
885-893
Date Issued
2009
Author(s)
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 (Ps0.05). 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. ? 2009 Nature Publishing Group.
Subjects
Allele; Dopamine; Haplotype; Linkage disequilibrium; PBAT
SDGs
Other Subjects
dopamine 2 receptor; article; Chinese; controlled study; female; gene linkage disequilibrium; gene mapping; genetic risk; genetic variability; haplotype; human; male; priority journal; schizophrenia; single nucleotide polymorphism; Asian Continental Ancestry Group; Case-Control Studies; Cysteine; Family Health; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Linkage Disequilibrium; Male; Polymorphism, Single Nucleotide; Receptors, Dopamine D2; Risk; Schizophrenia; Serine; Taiwan
Type
journal article