Population-based linkage analysis of schizophrenia and bipolar case–control cohorts identifies a potential susceptibility locus on 19q13.
Saved in:
| Title: | Population-based linkage analysis of schizophrenia and bipolar case–control cohorts identifies a potential susceptibility locus on 19q13. |
|---|---|
| Authors: | Francks, C., Tozzi, F., Farmer, A., Vincent, J. B., Rujescu, D., St. Clair, D., Muglia, P. |
| Source: | Molecular Psychiatry. Mar2010, Vol. 15 Issue 3, p319-325. 7p. 2 Graphs. |
| Subjects: | Genotype-environment interaction, Genetic polymorphisms, Genomes, Gene mapping, Schizophrenia |
| Abstract: | Population-based linkage analysis is a new method for analysing genomewide single nucleotide polymorphism (SNP) genotype data in case–control samples, which does not assume a common disease, common variant model. The genome is scanned for extended segments that show increased identity-by-descent sharing within case–case pairs, relative to case–control or control–control pairs. The method is robust to allelic heterogeneity and is suited to mapping genes which contain multiple, rare susceptibility variants of relatively high penetrance. We analysed genomewide SNP datasets for two schizophrenia case–control cohorts, collected in Aberdeen (461 cases, 459 controls) and Munich (429 cases, 428 controls). Population-based linkage testing must be performed within homogeneous samples and it was therefore necessary to analyse the cohorts separately. Each cohort was first subjected to several procedures to improve genetic homogeneity, including identity-by-state outlier detection and multidimensional scaling analysis. When testing only cases who reported a positive family history of major psychiatric disease, consistent with a model of strongly penetrant susceptibility alleles, we saw a distinct peak on chromosome 19q in both cohorts that appeared in meta-analysis (P=0.000016) to surpass the traditional level for genomewide significance for complex trait linkage. The linkage signal was also present in a third case–control sample for familial bipolar disorder, such that meta-analysing all three datasets together yielded a linkage P=0.0000026. A model of rare but highly penetrant disease alleles may be more applicable to some instances of major psychiatric diseases than the common disease common variant model, and we therefore suggest that other genome scan datasets are analysed with this new, complementary method. [ABSTRACT FROM AUTHOR] |
| Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
|---|---|
| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 48161841 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Population-based linkage analysis of schizophrenia and bipolar case–control cohorts identifies a potential susceptibility locus on 19q13. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Francks%2C+C%2E%22">Francks, C.</searchLink><br /><searchLink fieldCode="AR" term="%22Tozzi%2C+F%2E%22">Tozzi, F.</searchLink><br /><searchLink fieldCode="AR" term="%22Farmer%2C+A%2E%22">Farmer, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Vincent%2C+J%2E+B%2E%22">Vincent, J. B.</searchLink><br /><searchLink fieldCode="AR" term="%22Rujescu%2C+D%2E%22">Rujescu, D.</searchLink><br /><searchLink fieldCode="AR" term="%22St%2E+Clair%2C+D%2E%22">St. Clair, D.</searchLink><br /><searchLink fieldCode="AR" term="%22Muglia%2C+P%2E%22">Muglia, P.</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Molecular+Psychiatry%22">Molecular Psychiatry</searchLink>. Mar2010, Vol. 15 Issue 3, p319-325. 7p. 2 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Genotype-environment+interaction%22">Genotype-environment interaction</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+polymorphisms%22">Genetic polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Genomes%22">Genomes</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+mapping%22">Gene mapping</searchLink><br /><searchLink fieldCode="DE" term="%22Schizophrenia%22">Schizophrenia</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Population-based linkage analysis is a new method for analysing genomewide single nucleotide polymorphism (SNP) genotype data in case–control samples, which does not assume a common disease, common variant model. The genome is scanned for extended segments that show increased identity-by-descent sharing within case–case pairs, relative to case–control or control–control pairs. The method is robust to allelic heterogeneity and is suited to mapping genes which contain multiple, rare susceptibility variants of relatively high penetrance. We analysed genomewide SNP datasets for two schizophrenia case–control cohorts, collected in Aberdeen (461 cases, 459 controls) and Munich (429 cases, 428 controls). Population-based linkage testing must be performed within homogeneous samples and it was therefore necessary to analyse the cohorts separately. Each cohort was first subjected to several procedures to improve genetic homogeneity, including identity-by-state outlier detection and multidimensional scaling analysis. When testing only cases who reported a positive family history of major psychiatric disease, consistent with a model of strongly penetrant susceptibility alleles, we saw a distinct peak on chromosome 19q in both cohorts that appeared in meta-analysis (P=0.000016) to surpass the traditional level for genomewide significance for complex trait linkage. The linkage signal was also present in a third case–control sample for familial bipolar disorder, such that meta-analysing all three datasets together yielded a linkage P=0.0000026. A model of rare but highly penetrant disease alleles may be more applicable to some instances of major psychiatric diseases than the common disease common variant model, and we therefore suggest that other genome scan datasets are analysed with this new, complementary method. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=48161841 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/mp.2008.100 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 7 StartPage: 319 Subjects: – SubjectFull: Genotype-environment interaction Type: general – SubjectFull: Genetic polymorphisms Type: general – SubjectFull: Genomes Type: general – SubjectFull: Gene mapping Type: general – SubjectFull: Schizophrenia Type: general Titles: – TitleFull: Population-based linkage analysis of schizophrenia and bipolar case–control cohorts identifies a potential susceptibility locus on 19q13. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Francks, C. – PersonEntity: Name: NameFull: Tozzi, F. – PersonEntity: Name: NameFull: Farmer, A. – PersonEntity: Name: NameFull: Vincent, J. B. – PersonEntity: Name: NameFull: Rujescu, D. – PersonEntity: Name: NameFull: St. Clair, D. – PersonEntity: Name: NameFull: Muglia, P. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 03 Text: Mar2010 Type: published Y: 2010 Identifiers: – Type: issn-print Value: 13594184 Numbering: – Type: volume Value: 15 – Type: issue Value: 3 Titles: – TitleFull: Molecular Psychiatry Type: main |
| ResultId | 1 |
