Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.
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Author
Andlauer, Till F MGuzman-Parra, Jose
Streit, Fabian
Strohmaier, Jana
González, Maria José
Gil Flores, Susana
Cabaleiro Fabeiro, Francisco J
Del Río Noriega, Francisco
Perez, Fermin Perez
Haro González, Jesus
Orozco Diaz, Guillermo
de Diego-Otero, Yolanda
Moreno-Küstner, Berta
Auburger, Georg
Degenhardt, Franziska
Heilmann-Heimbach, Stefanie
Herms, Stefan
Hoffmann, Per
Frank, Josef
Foo, Jerome C
Treutlein, Jens
Witt, Stephanie H
Cichon, Sven
Kogevinas, Manolis
Rivas, Fabio
Mayoral, Fermín
Müller-Myhsok, Bertram
Forstner, Andreas J
Nöthen, Markus M
Rietschel, Marcella
Journal title
Molecular psychiatryDate Published
2019-11-11Publication Volume
26Publication Issue
4Publication Begin page
1286Publication End page
1298
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Show full item recordAbstract
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.Citation
Andlauer TFM, Guzman-Parra J, Streit F, Strohmaier J, González MJ, Gil Flores S, Cabaleiro Fabeiro FJ, Del Río Noriega F, Perez FP, Haro González J, Orozco Diaz G, de Diego-Otero Y, Moreno-Küstner B, Auburger G, Degenhardt F, Heilmann-Heimbach S, Herms S, Hoffmann P, Frank J, Foo JC, Treutlein J, Witt SH, Cichon S, Kogevinas M; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Rivas F, Mayoral F, Müller-Myhsok B, Forstner AJ, Nöthen MM, Rietschel M. Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders. Mol Psychiatry. 2021 Apr;26(4):1286-1298. doi: 10.1038/s41380-019-0558-2. Epub 2019 Nov 11. PMID: 31712721; PMCID: PMC7985020.DOI
10.1038/s41380-019-0558-2ae974a485f413a2113503eed53cd6c53
10.1038/s41380-019-0558-2
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Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International
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