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Publications [#273504] of Richard S. Keefe

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Journal Articles

  1. Sim, K; Lee, J; Subramaniam, M; Liu, JJ; Keefe, R; Zhang, XD; Lee, TS; Chong, SA (2011). Integrated genetic and genomic approach in the Singapore translational and clinical research in psychosis study: An overview. Early Intervention in Psychiatry, 5(2), 91-99. [doi]
    (last updated on 2019/02/20)

    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.


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