title: Integrated genetic and genomic approach in the SingaporeTranslational and Clinical Research in Psychosis Study: an overview.
abstract: OBJECTIVE
  Schizophrenia is a severe mental disorder with onset frequently in adolescence and followed by a chronic and disabling course. Although the exact pathophysiology of this devastating disorder has not been clearly elucidated, a large part of it has been attributed to genetic influences. This article seeks to provide an overview on what our group has embarked on--to elucidate genetic risk factors for schizophrenia within the Chinese ethnic group.
  
  
  METHODS
  We plan to conduct an integrated approach to interrogate comprehensively the genome from different angles and in stages. The first stage involves a genome-wide association study of 1000 cases of schizophrenia-control pairs, with a follow-up replication study in another 1000 cases of schizophrenia and in 1000 controls, and combination analyses with groups from other places including China and Hong Kong. Other than the genome-wide association study, gene sequencing for purported candidate genes and copy number variation analysis will be performed. Neurocognitive intermediate phenotypes will be employed to deconstruct the complex schizophrenia phenotype in a bid to improve association findings. Promising leads from longitudinal gene and protein expression in ultra-high-risk subjects who develop psychosis and schizophrenia (in a parallel study) will be followed up as candidate genes and sequenced in the genetic analysis. Functional analysis forms the last stage of this integrated approach.
  
  
  CONCLUSIONS
  This integrated genetic and genomic approach will hopefully help in further characterizing and deepening our understanding of molecular pathophysiological mechanisms underlying schizophrenia.
authors.affiliation: Department of General Psychiatry, Woodbridge Hospital/Institute of Mental Health Research Division, Singapore. kang_sim@imh.com.sg
authors.forename: Kang
authors.initials: K
authors.lastname: Sim
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lee
authors.forename: Mythily
authors.initials: M
authors.lastname: Subramaniam
authors.forename: Jian Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Richard
authors.initials: R
authors.lastname: Keefe
authors.forename: Xiao Dong
authors.initials: XD
authors.lastname: Zhang
authors.forename: Tih Shih
authors.initials: TS
authors.lastname: Lee
authors.forename: Siow Ann
authors.initials: SA
authors.lastname: Chong
mesh_terms: D044466:Asian People / Q000235:genetics / Q000523:psychology; D003071:Cognition; D020022:Genetic Predisposition to Disease / Q000235:genetics* / Q000523:psychology*; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D012107:Research Design; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology; D012846:Singapore; D057170:Translational Research, Biomedical / Q000379:methods*