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Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders


Title: Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders
Author: Andlauer, Till F. M.
Sigurdsson, Engilbert   orcid.org/0000-0001-9404-7982
Stefansson, Kari   orcid.org/0000-0003-1676-864X
Date: 2019-11-11
Language: English
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Læknadeild (HÍ)
Faculty of Medicine (UI)
Series: Molecular Psychiatry;2019
ISSN: 1359-4184
1476-5578 (eISSN)
DOI: 10.1038/s41380-019-0558-2
Subject: Psychiatric disorder; Genetic variants; Bipolar disorder; Schizophrenia; Depression; Geðraskanir; Þunglyndi; Geðklofi; Geðhvarfasýki; Genarannsóknir
URI: https://hdl.handle.net/20.500.11815/1896

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Citation:

Andlauer, T.F.M., Guzman-Parra, J., Streit, F. et al. Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders. Molecular Psychiatry (2019). https://doi.org/10.1038/s41380-019-0558-2

Abstract:

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.

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Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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