Common and rare variant analysis in early-onset bipolar disorder vulnerability

Jamain, Stéphane and Cichon, Sven and Etain, Bruno and Muhleisen, Thomas W. and Georgi, Alexander and Zidane, Nora and Chevallier, Lucie and Deshommes, Jasmine and Nicolas, Aude and Henrion, Annabelle and Degenhardt, Franziska and Mattheisen, Manuel and Priebe, Lutz and Mathieu, Flavie and Kahn, Jean-Pierre and Henry, Chantal and Boland, Anne and Zelenika, Diana and Gut, Ivo and Heath, Simon and Lathrop, Mark and Maier, Wolfgang and Albus, Margot and Rietschel, Marcella and Schulze, Thomas G. and McMahon, Francis J. and Kelsoe, John R. and Hamshere, Marian and Craddock, Nicholas and Nothen, Markus M. and Bellivier, Frank and Leboyer, Marion. (2014) Common and rare variant analysis in early-onset bipolar disorder vulnerability. PLoS ONE, 9 (8). e104326.

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Official URL: https://edoc.unibas.ch/61557/

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Bipolar disorder is one of the most common and devastating psychiatric disorders whose mechanisms remain largely unknown. Despite a strong genetic contribution demonstrated by twin and adoption studies, a polygenic background influences this multifactorial and heterogeneous psychiatric disorder. To identify susceptibility genes on a severe and more familial sub-form of the disease, we conducted a genome-wide association study focused on 211 patients of French origin with an early age at onset and 1,719 controls, and then replicated our data on a German sample of 159 patients with early-onset bipolar disorder and 998 controls. Replication study and subsequent meta-analysis revealed two genes encoding proteins involved in phosphoinositide signalling pathway (PLEKHA5 and PLCXD3). We performed additional replication studies in two datasets from the WTCCC (764 patients and 2,938 controls) and the GAIN-TGen cohorts (1,524 patients and 1,436 controls) and found nominal P-values both in the PLCXD3 and PLEKHA5 loci with the WTCCC sample. In addition, we identified in the French cohort one affected individual with a deletion at the PLCXD3 locus and another one carrying a missense variation in PLCXD3 (p.R93H), both supporting a role of the phosphatidylinositol pathway in early-onset bipolar disorder vulnerability. Although the current nominally significant findings should be interpreted with caution and need replication in independent cohorts, this study supports the strategy to combine genetic approaches to determine the molecular mechanisms underlying 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
Publisher:Public Library of Science
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Jul 2020 14:34
Deposited On:20 Jul 2020 14:34

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