Navigation überspringen
Universitätsbibliothek Heidelberg
Status: Bibliographieeintrag

Verfügbarkeit
Standort: ---
Exemplare: ---
heiBIB
 Online-Ressource
Verfasst von:Chang, Hong [VerfasserIn]   i
 Rietschel, Marcella [VerfasserIn]   i
Titel:Identification of a bipolar disorder vulnerable gene CHDH at 3p21.1
Verf.angabe:Hong Chang, Lingyi Li, Tao Peng, Maria Grigoroiu-Serbanescu, Sarah E. Bergen, Mikael Landén, Christina M. Hultman, Andreas J. Forstner, Jana Strohmaier, Julian Hecker, Thomas G. Schulze, Bertram Müller-Myhsok, Andreas Reif, Philip B. Mitchell, Nicholas G. Martin, Sven Cichon, Markus M. Nöthen, Stéphane Jamain, Marion Leboyer, Frank Bellivier, Bruno Etain, Jean-Pierre Kahn, Chantal Henry, Marcella Rietschel, The Swedish Bipolar Study Group, MooDS Consortium, Xiao Xiao, Ming Li
Jahr:2017
Jahr des Originals:2016
Umfang:11 S.
Fussnoten:Published online: 25 August 2016 ; Gesehen am 03.07.2018
Titel Quelle:Enthalten in: Molecular neurobiology
Ort Quelle:Totowa, NJ : Humana Press, 1987
Jahr Quelle:2017
Band/Heft Quelle:54(2017), 7, Seite 5166-5176
ISSN Quelle:1559-1182
Abstract:Genome-wide analysis (GWA) is an effective strategy to discover extreme effects surpassing genome-wide significant levels in studying complex disorders; however, when sample size is limited, the true effects may fail to achieve genome-wide significance. In such case, there may be authentic results among the pools of nominal candidates, and an alternative approach is to consider nominal candidates but are replicable across different samples. Here, we found that mRNA expression of the choline dehydrogenase gene (CHDH) was uniformly upregulated in the brains of bipolar disorder (BPD) patients compared with healthy controls across different studies. Follow-up genetic analyses of CHDH variants in multiple independent clinical datasets (including 11,564 cases and 17,686 controls) identified a risk SNP rs9836592 showing consistent associations with BPD (P meta = 5.72 × 10−4), and the risk allele indicated an increased CHDH expression in multiple neuronal tissues (lowest P = 6.70 × 10−16). These converging results may identify a nominal but true BPD susceptibility gene CHDH. Further exploratory analysis revealed suggestive associations of rs9836592 with childhood intelligence (P = 0.044) and educational attainment (P = 0.0039), a “proxy phenotype” of general cognitive abilities. Intriguingly, the CHDH gene is located at chromosome 3p21.1, a risk region implicated in previous BPD genome-wide association studies (GWAS), but CHDH is lying outside of the core GWAS linkage disequilibrium (LD) region, and our studied SNP rs9836592 is ∼1.2 Mb 3′ downstream of the previous GWAS loci (e.g., rs2251219) with no LD between them; thus, the association observed here is unlikely a reflection of previous GWAS signals. In summary, our results imply that CHDH may play a previously unknown role in the etiology of BPD and also highlight the informative value of integrating gene expression and genetic code in advancing our understanding of its biological basis.
DOI:doi:10.1007/s12035-016-0041-x
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: http://dx.doi.org/10.1007/s12035-016-0041-x
 Volltext: http://link.springer.com/article/10.1007/s12035-016-0041-x
 DOI: https://doi.org/10.1007/s12035-016-0041-x
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:157724012X
Verknüpfungen:→ Zeitschrift

Permanenter Link auf diesen Titel (bookmarkfähig):  https://katalog.ub.uni-heidelberg.de/titel/68280152   QR-Code
zum Seitenanfang