Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.

Détails

Ressource 1Télécharger: BIB_06BCD9AF75A3.P001.pdf (1875.62 [Ko])
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_06BCD9AF75A3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.
Périodique
British Journal of Psychiatry : the Journal of Mental Science
Auteur(s)
Li M., Luo X.J., Landén M., Bergen S.E., Hultman C.M., Li X., Zhang W., Yao Y.G., Zhang C., Liu J., Mattheisen M., Cichon S., Mühleisen T.W., Degenhardt F.A., Nöthen M.M., Schulze T.G., Grigoroiu-Serbanescu M., Li H., Fuller C.K., Chen C., Dong Q., Chen C., Jamain S., Leboyer M., Bellivier F., Etain B., Kahn J.P., Henry C., Preisig M., Kutalik Z., Castelao E., Wright A., Mitchell P.B., Fullerton J.M., Schofield P.R., Montgomery G.W., Medland S.E., Gordon S.D., Martin N.G., Rietschel M., Rietschel M., Liu C., Kleinman J.E., Hyde T.M., Weinberger D.R., Su B.
Collaborateur(s)
MooDS Consortium, Swedish Bipolar Study Group
ISSN
1472-1465 (Electronic)
ISSN-L
0007-1250
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
208
Numéro
2
Pages
128-137
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
BackgroundBipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.AimsWe sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.MethodTo detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54×10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.ConclusionsOur findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/02/2016 10:11
Dernière modification de la notice
20/08/2019 13:29
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