Document Detail


A large-scale candidate gene analysis of mood disorders: evidence of neurotrophic tyrosine kinase receptor and opioid receptor signaling dysfunction.
MedLine Citation:
PMID:  23277131     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Despite proven heritability, little is known about the genetic architecture of mood disorders. Although a number of family and case-control studies have examined the genetics of mood disorders, none have carried out joint linkage-association studies and sought to validate the results with gene expression analyses in an independent cohort.
METHODS: We present findings from a large candidate gene study that combines linkage and association analyses using families and singletons, providing a systematic candidate gene investigation of mood disorder. For this study, 876 individuals were recruited, including 83 families with 313 individuals and 563 singletons. This large-scale candidate gene analysis included 130 candidate genes implicated in addictive and other psychiatric disorders. These data showed significant genetic associations for 28 of these candidate genes, although none remained significant after correction for multiple testing. To evaluate the functional significance of these 28 candidate genes in mood disorders, we examined the transcriptional profiles of these genes within the dorsolateral prefrontal cortex and anterior cingulate for 21 cases with mood disorders and 25 nonpsychiatric controls, and carried out a pathway analysis to identify points of high connectivity suggestive of particular molecular pathways that may be dysregulated.
RESULTS: Two primary gene candidates were supported by the linkage-association, gene expression profiling, and network analysis: neurotrophic tyrosine kinase receptor, type 2 (NTRK2), and the opioid receptor, κ1 (OPRK1).
CONCLUSION: This study supports a role for NTRK2 and OPRK1 signaling in the pathophysiology of mood disorder. The unique approach incorporating evidence from multiple experimental and computational modalities enhances confidence in these findings.
Authors:
Anthony J Deo; Yung-yu Huang; Colin A Hodgkinson; Yurong Xin; Maria A Oquendo; Andrew J Dwork; Victoria Arango; David A Brent; David Goldman; J John Mann; Fatemeh Haghighi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Psychiatric genetics     Volume:  23     ISSN:  1473-5873     ISO Abbreviation:  Psychiatr. Genet.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-02-25     Completed Date:  2013-10-22     Revised Date:  2014-05-16    
Medline Journal Info:
Nlm Unique ID:  9106748     Medline TA:  Psychiatr Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  47-55     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Female
Gene Expression Profiling
Gene Regulatory Networks / genetics
Genes, Recessive / genetics
Genetic Association Studies*
Genetic Predisposition to Disease*
Humans
Male
Models, Genetic
Mood Disorders / genetics*
Receptor, trkB / genetics*
Receptors, Opioid, kappa / genetics*
Signal Transduction / genetics*
Grant Support
ID/Acronym/Agency:
K22 HG002915/HG/NHGRI NIH HHS; K22 HG2915/HG/NHGRI NIH HHS; MH074118/MH/NIMH NIH HHS; MH40210/MH/NIMH NIH HHS; MH48514/MH/NIMH NIH HHS; MH59710/MH/NIMH NIH HHS; MH62185/MH/NIMH NIH HHS; MH64168/MH/NIMH NIH HHS; P50 MH062185/MH/NIMH NIH HHS; R01 MH040210/MH/NIMH NIH HHS; R01 MH048514/MH/NIMH NIH HHS; R01 MH059710/MH/NIMH NIH HHS; R01 MH064168/MH/NIMH NIH HHS; R01 MH074118/MH/NIMH NIH HHS; Z01 AA000306-02/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/OPRK1 protein, human; 0/Receptors, Opioid, kappa; EC 2.7.10.1/Receptor, trkB
Comments/Corrections

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


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