Integrated genetic and genomic approach in the SingaporeTranslational and Clinical Research in Psychosis Study: an overview.

Journal Article

AIMS: 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. CONCLUSION: This integrated genetic and genomic approach will hopefully help in further characterizing and deepening our understanding of molecular pathophysiological mechanisms underlying schizophrenia.

Full Text

Duke Authors

Cited Authors

  • Sim, K; Lee, J; Subramaniam, M; Liu, JJ; Keefe, R; Zhang, XD; Lee, TS; Chong, SA

Published Date

  • May 2011

Published In

Volume / Issue

  • 5 / 2

Start / End Page

  • 91 - 99

PubMed ID

  • 21535421

Pubmed Central ID

  • 21535421

Electronic International Standard Serial Number (EISSN)

  • 1751-7893

Digital Object Identifier (DOI)

  • 10.1111/j.1751-7893.2011.00272.x


  • eng

Conference Location

  • Australia