Document Detail

Prioritization and association analysis of murine-derived candidate genes in anxiety-spectrum disorders.
MedLine Citation:
PMID:  21871609     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Anxiety disorders are common psychiatric conditions that are highly comorbid with each other and related phenotypes such as depression, likely due to a shared genetic basis. Fear-related behaviors in mice have long been investigated as potential models of anxiety disorders, making integration of information from both murine and human genetic data a powerful strategy for identifying potential susceptibility genes for these conditions.
METHODS: We combined genome-wide association analysis of fear-related behaviors with strain distribution pattern analysis in heterogeneous stock mice to identify a preliminary list of 52 novel candidate genes. We ranked these according to three complementary sources of prior anxiety-related genetic data: 1) extant linkage and knockout studies in mice, 2) a meta-analysis of human linkage scans, and 3) a preliminary human genome-wide association study. We genotyped tagging single nucleotide polymorphisms covering the nine top-ranked regions in a two-stage association study of 1316 subjects from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders chosen for high or low genetic loading for anxiety-spectrum phenotypes (anxiety disorders, neuroticism, and major depression).
RESULTS: Multiple single nucleotide polymorphisms in the PPARGC1A gene demonstrated association in both stages that survived gene-wise correction for multiple testing.
CONCLUSIONS: Integration of genetic data across human and murine studies suggests PPARGC1A as a potential susceptibility gene for anxiety-related disorders.
John M Hettema; Bradley T Webb; An-Yuan Guo; Zhongming Zhao; Brion S Maher; Xiangning Chen; Seon-Sook An; Cuie Sun; Steven H Aggen; Kenneth S Kendler; Po-Hsiu Kuo; Takeshi Otowa; Jonathan Flint; Edwin J van den Oord
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Publication Detail:
Type:  Journal Article; Meta-Analysis; Research Support, N.I.H., Extramural; Twin Study     Date:  2011-08-25
Journal Detail:
Title:  Biological psychiatry     Volume:  70     ISSN:  1873-2402     ISO Abbreviation:  Biol. Psychiatry     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-11     Completed Date:  2012-02-01     Revised Date:  2014-02-24    
Medline Journal Info:
Nlm Unique ID:  0213264     Medline TA:  Biol Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  888-96     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Anxiety Disorders / genetics*
Behavior, Animal
Data Interpretation, Statistical
Databases, Genetic
Diagnostic and Statistical Manual of Mental Disorders
Fear / physiology,  psychology
Genetic Linkage
Genome-Wide Association Study
Heat-Shock Proteins / genetics
Mice, Knockout
Polymorphism, Single Nucleotide
Transcription Factors / genetics
Grant Support
079912//Wellcome Trust; 090532//Wellcome Trust; R01 MH59565/MH/NIMH NIH HHS; R01 MH59566/MH/NIMH NIH HHS; R01 MH59571/MH/NIMH NIH HHS; R01 MH59586/MH/NIMH NIH HHS; R01 MH59587/MH/NIMH NIH HHS; R01 MH59588/MH/NIMH NIH HHS; R01 MH60870/MH/NIMH NIH HHS; R01 MH60879/MH/NIMH NIH HHS; R01 MH61675/MH/NIMH NIH HHS; R01 MH67257/MH/NIMH NIH HHS; R21 MH079192-02/MH/NIMH NIH HHS; R21MH79192/MH/NIMH NIH HHS; U01 MH046276/MH/NIMH NIH HHS; U01 MH46289/MH/NIMH NIH HHS; U01 MH46318/MH/NIMH NIH HHS; U01 MH79469/MH/NIMH NIH HHS; U01 MH79470/MH/NIMH NIH HHS; UL1 RR031990/RR/NCRR NIH HHS; UL1RR031990/RR/NCRR NIH HHS
Reg. No./Substance:
0/Heat-Shock Proteins; 0/PPARGC1A protein, human; 0/Transcription Factors

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