Journal Article

FZJ-2015-05616

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance

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.FZJ* ; 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. ; Consortium, M. (Collaboration Author) ; Group, S. B. S. (Collaboration Author) ; Rietschel, M. ; Liu, C. ; Kleinman, J. E. ; Hyde, T. M. ; Weinberger, D. R. ; Su, B. (Corresponding author)

2016
Royal College of Psychiatrists London

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Please use a persistent id in citations: http://hdl.handle.net/2128/19365  doi:10.1192/bjp.bp.114.156976

Abstract: 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.

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Contributing Institute(s):

1. Strukturelle und funktionelle Organisation des Gehirns (INM-1)

Research Program(s):

1. 571 - Connectivity and Activity (POF3-571) (POF3-571)

Appears in the scientific report 2016

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