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A systematic genomewide linkage study in 353 sib pairs with schizophrenia.
Umeå University, Faculty of Medicine, Clinical Sciences.
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2003 (English)In: American Journal of Human Genetics, ISSN 0002-9297, Vol. 73, no 6, 1355-1367 p.Article in journal (Refereed) Published
Abstract [en]

We undertook a genomewide linkage study in a total of 353 affected sib pairs (ASPs) with schizophrenia. Our sample consisted of 179 ASPs from the United Kingdom, 134 from Sweden, and 40 from the United States. We typed 372 microsatellite markers at approximately 10-cM intervals. Our strongest finding was a LOD score of 3.87 on chromosome 10q25.3-q26.3, with positive results being contributed by all three samples and a LOD-1 interval of 15 cM. This finding achieved genomewide significance (P<.05), on the basis of simulation studies. We also found two regions, 17p11.2-q25.1 (maximum LOD score [MLS] = 3.35) and 22q11 (MLS = 2.29), in which the evidence for linkage was highly suggestive. Linkage to all of these regions has been supported by other studies. Moreover, we found strong evidence for linkage (genomewide P<.02) to 17p11.2-q25.1 in a single pedigree with schizophrenia. In our view, the evidence is now sufficiently compelling to undertake detailed mapping studies of these three regions.

Place, publisher, year, edition, pages
2003. Vol. 73, no 6, 1355-1367 p.
URN: urn:nbn:se:umu:diva-27109DOI: 10.1086/380206PubMedID: 14628288OAI: diva2:276198
Available from: 2009-11-11 Created: 2009-11-11 Last updated: 2009-11-11
In thesis
1. Diagnostic Evaluation of Schizophrenia for Genetic Studies
Open this publication in new window or tab >>Diagnostic Evaluation of Schizophrenia for Genetic Studies
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Schizophrenia is one of the most severe mental disorders. Heredity is accepted as a major causative factor. To find molecular mechanisms behind schizophrenia, patient materials with reliable and valid diagnoses must be identified. In order to compare schizophrenia diagnostic procedures for reliability, validity and suitability for genetic studies by evaluation of record information, interview and register diagnostic data and to examine patient materials for linkage or association with molecular genetic markers three patient materials were recruited: sporadic cases, a large pedigree and sib-pairs.

Schizophrenia diagnoses based on patient records only, showed good to excellent agreement with diagnoses based on both records and interviews. Register diagnoses generally displayed poor agreement with research diagnoses, but in 94% of patients sometimes registered as schizophrenic psychoses a research diagnosis of these disorders was certified. In the pedigree, analysis suggested linkage to chr 6p23 in a single branch of the pedigree, and a genome scan indicated linkage to the 6q25 region. A genome scan analysis of the sib-pair material was suggestive of linkage to chr 10q25.3-q26.3. In the case-control sample and a meta-analysis there was an association between a dopamine D2 receptor polymorphism (Ser311Cys), on chr 11q22-23, and the disorder. Brain-derived neurotrophic factor gene variants (chr 11p13) were also analysed without any robust significant findings.

For patients in long-term treatment for schizophrenia in Sweden, psychiatric record reviews should be valid, reliable and sufficient for assessment of lifetime research diagnosis. Swedish register diagnosis of schizophrenic psychoses has a high positive predictive power in relation to corresponding research diagnoses. For future Swedish studies focusing on a broad definition of schizophrenia, it is sufficient to rely on the register diagnoses of schizophrenic psychosis. There is no major vulnerability gene or locus that is common to the majority of patients with schizophrenia, indicating genetic heterogeneity.

Place, publisher, year, edition, pages
Umeå: Klinisk vetenskap, 2005. 70 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 993
Psychiatry, Schizophrenia, Diagnostic evaluation, Molecular genetic studies, Linkage, Association, Psykiatri
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Research subject
urn:nbn:se:umu:diva-637 (URN)91-7305-970-6 (ISBN)
Public defence
2005-12-09, D, Tandläkarhögskolan, Norrlands universitetssjukhus, Umeå, 09:00 (English)
Available from: 2005-11-17 Created: 2005-11-17 Last updated: 2010-05-06Bibliographically approved

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