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Early Interv Psychiatry. 2011 May;5(2):91-9. doi: 10.1111/j.1751-7893.2011.00272.x.

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

Author information

  • 1Department of General Psychiatry, Woodbridge Hospital/Institute of Mental Health Research Division, Singapore. kang_sim@imh.com.sg

Abstract

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.

© 2011 Blackwell Publishing Asia Pty Ltd.

PMID:
21535421
[PubMed - indexed for MEDLINE]
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