Document Detail


White matter integrity as an intermediate phenotype: exploratory genome-wide association analysis in individuals at high risk of bipolar disorder.
MedLine Citation:
PMID:  23218918     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-04
Journal Detail:
Title:  Psychiatry research     Volume:  206     ISSN:  1872-7123     ISO Abbreviation:  Psychiatry Res     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-01     Completed Date:  2013-09-17     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  7911385     Medline TA:  Psychiatry Res     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  223-31     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Bipolar Disorder / genetics*,  physiopathology
Brain / physiology*,  physiopathology
Case-Control Studies
Diffusion Tensor Imaging
Endophenotypes
Family
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Image Processing, Computer-Assisted
Male
Models, Genetic
Nerve Fibers, Myelinated / physiology*
Polymorphism, Single Nucleotide
Risk
Young Adult
Grant Support
ID/Acronym/Agency:
G0600429//Medical Research Council; //Chief Scientist Office; //Wellcome Trust

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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