Literature DB >> 16203953

Genomewide linkage scan in schizoaffective disorder: significant evidence for linkage at 1q42 close to DISC1, and suggestive evidence at 22q11 and 19p13.

Marian L Hamshere1, Phil Bennett, Nigel Williams, Ricardo Segurado, Alastair Cardno, Nadine Norton, David Lambert, Hywel Williams, George Kirov, Aiden Corvin, Peter Holmans, Lisa Jones, Ian Jones, Michael Gill, Michael C O'Donovan, Michael J Owen, Nick Craddock.   

Abstract

CONTEXT: Traditionally, the search for genes involved in predisposition to major psychoses has proceeded with separate studies of schizophrenia and bipolar disorder. However, twin data suggest that, in addition to genes with specificity for these phenotypes, there exist genes that simultaneously influence susceptibility to schizophrenia, bipolar disorder, and schizoaffective disorder.
OBJECTIVE: To undertake, to our knowledge, the first systematic search for such loci.
DESIGN: Genomewide linkage scan.
SETTING: Affected individuals were ascertained in the United Kingdom and Ireland from general psychiatric inpatient and outpatient services. PARTICIPANTS: The families were selected for linkage studies of either schizophrenia or bipolar disorder. Pedigrees were selected for the current analysis where there was at least 1 member with DSM-IV schizoaffective disorder, bipolar type. Within these pedigrees, individuals were coded as affected if they had been diagnosed with DSM-IV schizophrenia, schizoaffective disorder of bipolar type, or bipolar I disorder. A total of 24 pedigrees contributed 35 affected sibling pairs to the sample.
METHOD: A 10-centimorgan genome scan using microsatellite markers was analyzed using MAPMAKER/SIBS software.
RESULTS: A genomewide significant signal (LOD = 3.54) was observed at chromosome 1q42 (near D1S2800), and suggestive LOD scores were observed at chromosomes 22q11 (LOD = 1.96) and 19p13 (LOD = 1.85). No linkage was observed in these regions in our original schizophrenia or bipolar scans in individuals from the United Kingdom.
CONCLUSIONS: Our linkage findings strongly support the existence of loci that influence susceptibility across the functional psychosis spectrum. The DISC1 gene lies within 2.5 megabases of our peak marker on chromosome 1q42 and has been previously implicated in schizophrenia, bipolar disorder, and, recently, schizoaffective disorder. Follow-up of this region should use samples enriched for cases of schizoaffective disorder. Our findings have similar implications for the search for genetic variation on chromosome 22q11 that influences susceptibility to psychosis.

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Year:  2005        PMID: 16203953     DOI: 10.1001/archpsyc.62.10.1081

Source DB:  PubMed          Journal:  Arch Gen Psychiatry        ISSN: 0003-990X


  62 in total

Review 1.  Genes and schizophrenia: beyond schizophrenia: the role of DISC1 in major mental illness.

Authors:  William Hennah; Pippa Thomson; Leena Peltonen; David Porteous
Journal:  Schizophr Bull       Date:  2006-05-12       Impact factor: 9.306

Review 2.  Schizoaffective disorder: a review of current research themes and pharmacological management.

Authors:  Joshua T Kantrowitz; Leslie Citrome
Journal:  CNS Drugs       Date:  2011-04       Impact factor: 5.749

3.  Rethinking psychosis: the disadvantages of a dichotomous classification now outweigh the advantages.

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Journal:  World Psychiatry       Date:  2007-06       Impact factor: 49.548

Review 4.  Comparing genes and phenomenology in the major psychoses: schizophrenia and bipolar 1 disorder.

Authors:  Elena Ivleva; Gunvant Thaker; Carol A Tamminga
Journal:  Schizophr Bull       Date:  2008-05-30       Impact factor: 9.306

5.  Convergent brain microstructure across multiple genetic models of schizophrenia and autism spectrum disorder: A feasibility study.

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Journal:  Magn Reson Imaging       Date:  2020-04-13       Impact factor: 2.546

Review 6.  Clinical perspectives on the genetics of schizophrenia: a bottom-up orientation.

Authors:  Willem M A Verhoeven; Siegfried Tuinier
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7.  Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain.

Authors:  Xin Duan; Jay H Chang; Shaoyu Ge; Regina L Faulkner; Ju Young Kim; Yasuji Kitabatake; Xiao-bo Liu; Chih-Hao Yang; J Dedrick Jordan; Dengke K Ma; Cindy Y Liu; Sundar Ganesan; Hwai-Jong Cheng; Guo-li Ming; Bai Lu; Hongjun Song
Journal:  Cell       Date:  2007-09-06       Impact factor: 41.582

8.  The schizophrenias, the neuroses and the covered wagon; a critical review.

Authors:  C Raymond Lake; Nathaniel Hurwitz
Journal:  Neuropsychiatr Dis Treat       Date:  2007-02       Impact factor: 2.570

9.  A novel analytical framework for dissecting the genetic architecture of behavioral symptoms in neuropsychiatric disorders.

Authors:  Anthony J Deo; Ramiro Costa; Lynn E DeLisi; Rob DeSalle; Fatemeh Haghighi
Journal:  PLoS One       Date:  2010-03-16       Impact factor: 3.240

10.  Top-down or bottom-up: Contrasting perspectives on psychiatric diagnoses.

Authors:  Willem Ma Verhoeven; Siegfried Tuinier; Ineke van der Burgt
Journal:  Biologics       Date:  2008-09
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