title: The genetic validation of heterogeneity in schizophrenia.
abstract: BACKGROUND
  Schizophrenia is a heritable disorder, however clear genetic architecture has not been detected. To overcome this state of uncertainty, the SZGene database has been established by including all published case-control genetic association studies appearing in peer-reviewed journals. In the current study, we aimed to determine if genetic variants strongly suggested by SZGene are associated with risk of schizophrenia in our case-control samples of Japanese ancestry. In addition, by employing the additive model for aggregating the effect of seven variants, we aimed to verify the genetic heterogeneity of schizophrenia diagnosed by an operative diagnostic manual, the DSM-IV.
  
  
  METHODS
  Each positively suggested genetic polymorphism was ranked according to its p-value, then the seven top-ranked variants (p < 0.0005) were selected from DRD2, DRD4, GRIN2B, TPH1, MTHFR, and DTNBP1 (February, 2007). 407 Schizophrenia cases and 384 controls participated in this study. To aggregate the vulnerability of the disorder based on the participants' genetic information, we calculated the "risk-index" by adding the number of genetic risk factors.
  
  
  RESULTS
  No statistically significant deviation between cases and controls was observed in the genetic risk-index derived from all seven variants on the top-ranked polymorphisms. In fact, the average risk-index score in the schizophrenia group (6.5+/-1.57) was slightly lower than among controls (6.6+/-1.39).
  
  
  CONCLUSIONS
  The current work illustrates the difficulty in identifying universal and definitive risk-conferring polymorphisms for schizophrenia. Our employed number of samples was small, so we can not preclude the possibility that some or all of these variants are minor risk factors for schizophrenia in the Japanese population. It is also important to aggregate the updated positive variants in the SZGene database when the replication work is conducted.
authors: Department of Neuropsychiatry, Osaka Medical College, Osaka, Japan.
authors: Atsushi
authors: A
authors: Tsutsumi
authors: Stephen J
authors: SJ
authors: Glatt
authors: Tetsufumi
authors: T
authors: Kanazawa
authors: Seiya
authors: S
authors: Kawashige
authors: Hiroyuki
authors: H
authors: Uenishi
authors: Akira
authors: A
authors: Hokyo
authors: Takao
authors: T
authors: Kaneko
authors: Makiko
authors: M
authors: Moritani
authors: Hiroki
authors: H
authors: Kikuyama
authors: Jun
authors: J
authors: Koh
authors: Hitoshi
authors: H
authors: Matsumura
authors: Hiroshi
authors: H
authors: Yoneda
mesh_terms: D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D030541:Databases, Genetic; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D009419:Nerve Tissue Proteins