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

Hamshere, Marian Lindsay ORCID: https://orcid.org/0000-0002-8990-0958, Williams, Nigel Melville ORCID: https://orcid.org/0000-0003-1177-6931, Norton, Nadine ORCID: https://orcid.org/0000-0002-3848-4288, Williams, H., Cardno, Alastair G., Zammit, Stanley ORCID: https://orcid.org/0000-0002-2647-9211, Jones, L. A., Murphy, K. C., Sanders, Rebecca, McCarthy, G., Gray, M. Y., Jones, G., Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 and Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610 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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Abstract

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:	27 Oct 2022 08:23
URI:	https://orca.cardiff.ac.uk/id/eprint/62138

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