 |
|
Genomewide Linkage Scan in Schizoaffective Disorder
Significant Evidence for Linkage at 1q42 Close to DISC1, and Suggestive Evidence at 22q11 and 19p13
Marian L. Hamshere, PhD;
Phil Bennett, PhD;
Nigel Williams, PhD;
Ricardo Segurado, PhD;
Alastair Cardno, PhD, MRCPsych;
Nadine Norton, PhD;
David Lambert, PhD;
Hywel Williams, PhD;
George Kirov, MD, MRCPsych;
Aiden Corvin, MD, MRCPsych;
Peter Holmans, PhD;
Lisa Jones, PhD;
Ian Jones, PhD, MRCPsych;
Michael Gill, MD, MRCPsych;
Michael C. O’Donovan, PhD, FRCPsych;
Michael J. Owen, PhD, FRCPsych;
Nick Craddock, PhD, FRCPsych
Arch Gen Psychiatry. 2005;62:1081-1088.
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.
Author Affiliations: Department of Psychological Medicine (Drs Hamshere, N. Williams, Cardno, Norton, H. Williams, Kirov, I. Jones, O’Donovan, Owen, and Craddock) and Biostatistics and Bioinformatics Unit (Drs Hamshere and Holmans), School of Medicine, Cardiff University, Cardiff, Wales; Division of Neuroscience, University of Birmingham, Queen Elizabeth Psychiatric Hospital, Birmingham, England (Drs Bennett and L. Jones); and Departments of Psychiatry and Genetics, Trinity College, Dublin, Ireland (Drs Segurado, Lambert, Corvin, and Gill).
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Comparing Genes and Phenomenology in the Major Psychoses: Schizophrenia and Bipolar 1 Disorder
Ivleva et al.
Schizophr Bull 2008;34:734-742.
FULL TEXT
Strong evidence that GNB1L is associated with schizophrenia
Williams et al.
Hum Mol Genet 2008;17:555-566.
ABSTRACT
| FULL TEXT
Family-Based Association Study of Lithium-Related and Other Candidate Genes in Bipolar Disorder
Perlis et al.
Arch Gen Psychiatry 2008;65:53-61.
ABSTRACT
| FULL TEXT
Association of distinct allelic haplotypes of DISC1 with psychotic and bipolar spectrum disorders and with underlying cognitive impairments
Palo et al.
Hum Mol Genet 2007;16:2517-2528.
ABSTRACT
| FULL TEXT
The Genetic Deconstruction of Psychosis
Owen et al.
Schizophr Bull 2007;33:905-911.
ABSTRACT
| FULL TEXT
Schizophrenia: a common disease caused by multiple rare alleles
McClellan et al.
Br. J. Psychiatry 2007;190:194-199.
ABSTRACT
| FULL TEXT
Phenotypic and genetic complexity of psychosis: Invited commentary on ... Schizophrenia: a common disease caused by multiple rare alleles
Craddock et al.
Br. J. Psychiatry 2007;190:200-203.
ABSTRACT
| FULL TEXT
DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1
Kamiya et al.
Hum Mol Genet 2006;15:3313-3323.
ABSTRACT
| FULL TEXT
Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling
Hashimoto et al.
Hum Mol Genet 2006;15:3024-3033.
ABSTRACT
| FULL TEXT
Genes and Schizophrenia: Beyond Schizophrenia: The Role of DISC1 in Major Mental Illness
Hennah et al.
Schizophr Bull 2006;32:409-416.
ABSTRACT
| FULL TEXT
Chromosomal abnormalities and psychosis
MUIR et al.
Br. J. Psychiatry 2006;188:501-503.
ABSTRACT
| FULL TEXT
Genes for Schizophrenia and Bipolar Disorder? Implications for Psychiatric Nosology
Craddock et al.
Schizophr Bull 2006;32:9-16.
ABSTRACT
| FULL TEXT
Are Schizophrenia and Bipolar Disorder Completely Different Conditions?
JWatch Psychiatry 2005;2005:5-5.
FULL TEXT
|
