title: The DAO gene is associated with schizophrenia and interacts with other genes in the Taiwan Han Chinese population.
abstract: BACKGROUND
  Schizophrenia is a highly heritable disease with a polygenic mode of inheritance. Many studies have contributed to our understanding of the genetic underpinnings of schizophrenia, but little is known about how interactions among genes affect the risk of schizophrenia. This study aimed to assess the associations and interactions among genes that confer vulnerability to schizophrenia and to examine the moderating effect of neuropsychological impairment.
  
  
  METHODS
  We analyzed 99 SNPs from 10 candidate genes in 1,512 subject samples. The permutation-based single-locus, multi-locus association tests, and a gene-based multifactorial dimension reduction procedure were used to examine genetic associations and interactions to schizophrenia.
  
  
  RESULTS
  We found that no single SNP was significantly associated with schizophrenia. However, a risk haplotype, namely A-T-C of the SNP triplet rsDAO7-rsDAO8-rsDAO13 of the DAO gene, was strongly associated with schizophrenia. Interaction analyses identified multiple between-gene and within-gene interactions. Between-gene interactions including DAO*DISC1 , DAO*NRG1 and DAO*RASD2 and a within-gene interaction for CACNG2 were found among schizophrenia subjects with severe sustained attention deficits, suggesting a modifying effect of impaired neuropsychological functioning. Other interactions such as the within-gene interaction of DAO and the between-gene interaction of DAO and PTK2B were consistently identified regardless of stratification by neuropsychological dysfunction. Importantly, except for the within-gene interaction of CACNG2, all of the identified risk haplotypes and interactions involved SNPs from DAO.
  
  
  CONCLUSIONS
  These results suggest that DAO, which is involved in the N-methyl-d-aspartate receptor regulation, signaling and glutamate metabolism, is the master gene of the genetic associations and interactions underlying schizophrenia. Besides, the interaction between DAO and RASD2 has provided an insight in integrating the glutamate and dopamine hypotheses of schizophrenia.
authors.affiliation: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Hsin-Chou
authors.initials: HC
authors.lastname: Yang
authors.forename: Chih-Min
authors.initials: CM
authors.lastname: Liu
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Liu
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Chen
authors.forename: Chien Ching
authors.initials: CC
authors.lastname: Chang
authors.forename: Cathy S J
authors.initials: CS
authors.lastname: Fann
authors.forename: Jen-Jie
authors.initials: JJ
authors.lastname: Chiou
authors.forename: Ueng-Cheng
authors.initials: UC
authors.lastname: Yang
authors.forename: Chun-Houh
authors.initials: CH
authors.lastname: Chen
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.forename: Hai-Gwo
authors.initials: HG
authors.lastname: Hwu
mesh_terms: D044466:Asian People / Q000235:genetics; D003605:D-Amino-Acid Oxidase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D013624:Taiwan
chemical_list: D003605:D-Amino-Acid Oxidase; D019204:GTP-Binding Proteins; C486702:RASD2 protein, human
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