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Genome wide significant linkage in schizophrenia conditioning on occurrence of depressive episodes

Hamshere, Marian Lindsay, Williams, Nigel Melville, Norton, Nadine, Williams, H., Cardno, Alastair G., Zammit, Stanley, Jones, L. A., Murphy, K. C., Sanders, Rebecca, McCarthy, G., Gray, M. Y., Jones, G., Holmans, Peter Alan, O'Donovan, Michael Conlon, Owen, Michael John and Craddock, Nicholas John 2006. Genome wide significant linkage in schizophrenia conditioning on occurrence of depressive episodes. Journal of Medical Genetics 43 (7) , pp. 563-567. 10.1136/jmg.2005.035345

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Background: Schizophrenia shows substantial clinical heterogeneity. One common important clinical variable in presentation is the occurrence of episodes of major depression. Methods: We undertook analyses in an attempt to detect loci that influence susceptibility to, or modify the clinical expression of, schizophrenia according to the occurrence of episodes of major depression. We used a logistic regression framework in which lifetime presence/absence of major depression was entered as a covariate in the linkage analysis of our UK schizophrenia affected sibling pair series (168 affected sibling pairs typed for a 10 cM map of microsatellite markers). Results: Inclusion of presence/absence of depression as a covariate detected a genome wide significant linkage signal on chromosome 4q28.3 at 130.7 cM (LOD = 4.59; p = 0.038; increase in maximum LOD over univariate analysis (ILOD) = 3.62). Inclusion of the depression covariate also showed suggestive evidence of linkage on 20q11.21 (LOD = 4.10; expected to occur by chance 0.093 times per genome scan, ILOD = 2.83). Conclusions: Our findings identify loci that may harbour genes that play a role in susceptibility to, or modify the risk of, episodes of major depression in people with schizophrenia.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
Publisher: BMJ
ISSN: 1468-6244
Last Modified: 16 Mar 2020 14:22

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