| White matter integrity as an intermediate phenotype: Exploratory genome-wide association analysis in individuals at high risk of bipolar disorder. | |
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MedLine Citation:
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PMID: 23218918 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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White matter integrity, as measured using diffusion tensor imaging (DTI), is reduced in individuals with bipolar disorder (BD), their unaffected relatives and carriers of specific risk-alleles. Fractional anisotropy (FA), an index of white matter integrity, is highly heritable but the genetic architecture of this trait has received little investigation. In this study we performed a genome-wide association study with FA as quantitative phenotype, in unaffected relatives of patients with BD (N=70) and a matched control group (N=80). Amongst our top results were SNPs located in genes involved in cell adhesion, white matter development and neuronal plasticity. Pathway analysis of the top associated polymorphisms and genes confirmed the enrichment of processes relevant to BD and white matter development, including axon guidance, ErbB-signalling neurotrophin signalling, phosphatidylinositol signalling, and cell adhesion. The majority of genes implicated in these pathways were differentially associated with FA in individuals at high familial risk, suggesting interactions with genetic background or environmental factors secondary to familial risk for BD. Although the present findings require independent replication, the results encourage the use of global FA as a quantitative phenotype in future large-scale studies which may help to identify the biological processes underlying reduced FA in BD and other psychiatric disorders. |
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Authors:
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Emma Sprooten; Kathryn M Fleming; Pippa A Thomson; Mark E Bastin; Heather C Whalley; Jeremy Hall; Jess E Sussmann; James McKirdy; Douglas Blackwood; Stephen M Lawrie; Andrew M McIntosh |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-12-4 |
Journal Detail:
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Title: Psychiatry research Volume: - ISSN: 1872-7123 ISO Abbreviation: Psychiatry Res Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7911385 Medline TA: Psychiatry Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Division of Psychiatry, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, UK. Electronic address: e.sprooten@ed.ac.uk. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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