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

Li, M. and Luo, X. J. and Landen, M. and Bergen, S. E. and Hultman, C. M. and Li, X. and Zhang, W. and Yao, Y. G. and Zhang, C. and Liu, J. and Mattheisen, M. and Cichon, S. and Muhleisen, T. W. and Degenhardt, F. A. and Nothen, M. M. and Schulze, T. G. and Grigoroiu-Serbanescu, M. and Li, H. and Fuller, C. K. and Chen, C. and Dong, Q. and Chen, C. and Jamain, S. and Leboyer, M. and Bellivier, F. and Etain, B. and Kahn, J. P. and Henry, C. and Preisig, M. and Kutalik, Z. and Castelao, E. and Wright, A. and Mitchell, P. B. and Fullerton, J. M. and Schofield, P. R. and Montgomery, G. W. and Medland, S. E. and Gordon, S. D. and Martin, N. G. and Moo, D. S. Consortium and Swedish Bipolar Study, Group and Rietschel, M. and Liu, C. and Kleinman, J. E. and Hyde, T. M. and Weinberger, D. R. and Su, B.. (2016) Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance. The British Journal of Psychiatry, 208 (2). pp. 128-137.

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Official URL: https://edoc.unibas.ch/61566/

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BACKGROUND: Bipolar 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. AIMS: We 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. METHOD: To 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. RESULTS: Integrative 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 x 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 x 10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals. CONCLUSIONS: Our 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Human Genetics (Cichon)
UniBasel Contributors:Cichon, Sven
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Apr 2019 15:44
Deposited On:16 Apr 2019 15:44

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