title: Association analyses of the interaction between the ADSS and ATM genes with schizophrenia in a Chinese population.
abstract: BACKGROUND
  The blood-derived RNA levels of the adenylosuccinate synthase (ADSS) and ataxia telangiectasia mutated (ATM) genes were found to be down- and up-regulated, respectively, in schizophrenics compared with controls, and ADSS and ATM were among eight biomarker genes to discriminate schizophrenics from normal controls. ADSS catalyzes the first committed step of AMP synthesis, while ATM kinase serves as a key signal transducer in the DNA double-strand breaks response pathway. It remains unclear whether these changes result from mutations or polymorphisms in the two genes.
  
  
  METHODS
  Six SNPs in the ADSS gene and three SNPs in the ATM gene in a Chinese population of 488 schizophrenics and 516 controls were genotyped to examine their association with schizophrenia (SZ). Genotyping was performed using the Sequenom platform.
  
  
  RESULTS
  There was no significant difference in the genotype, allele, or haplotype distributions of the nine SNPs between cases and controls. Using the Multifactor Dimensionality Reduction (MDR) method, we found that the interactions among rs3102460 in the ADSS gene and rs227061 and rs664143 in the ATM gene revealed a significant association with SZ. This model held a maximum testing accuracy of 60.4% and a maximum cross-validation consistency of 10 out of 10.
  
  
  CONCLUSIONS
  These findings suggest that the combined effects of the polymorphisms in the ADSS and ATM genes may confer susceptibility to the development of SZ in a Chinese population.
authors.affiliation: Institute of Neurological disorders, Tsinghua University, Department of Psychiatry, Yuquan Hospital, Tsinghua University, Bejing, 100049, PR China. zhfq@tsinghua.edu.cn
authors.forename: Fuquan
authors.initials: F
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Pozi
authors.initials: P
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Fan
authors.forename: Xuezhu
authors.initials: X
authors.lastname: Huang
authors.forename: Gaoxiang
authors.initials: G
authors.lastname: Sun
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Song
authors.forename: Pak C
authors.initials: PC
authors.lastname: Sham
mesh_terms: D000265:Adenylosuccinate Synthase / Q000235:genetics*; D000483:Alleles; D064007:Ataxia Telangiectasia Mutated Proteins; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D002681:China; D004268:DNA-Binding Proteins / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012313:RNA / Q000097:blood; D012559:Schizophrenia / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D025521:Tumor Suppressor Proteins; D012313:RNA; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D000265:Adenylosuccinate Synthase