RT Journal Article
T1 Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.
A1 Andlauer, Till F M
A1 Guzman-Parra, Jose
A1 Streit, Fabian
A1 Strohmaier, Jana
A1 González, Maria José
A1 Gil Flores, Susana
A1 Cabaleiro Fabeiro, Francisco J
A1 Del Río Noriega, Francisco
A1 Perez, Fermin Perez
A1 Haro González, Jesus
A1 Orozco Diaz, Guillermo
A1 de Diego-Otero, Yolanda
A1 Moreno-Küstner, Berta
A1 Auburger, Georg
A1 Degenhardt, Franziska
A1 Heilmann-Heimbach, Stefanie
A1 Herms, Stefan
A1 Hoffmann, Per
A1 Frank, Josef
A1 Foo, Jerome C
A1 Treutlein, Jens
A1 Witt, Stephanie H
A1 Cichon, Sven
A1 Kogevinas, Manolis
A1 Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, 
A1 Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 
A1 Rivas, Fabio
A1 Mayoral, Fermín
A1 Müller-Myhsok, Bertram
A1 Forstner, Andreas J
A1 Nöthen, Markus M
A1 Rietschel, Marcella
AB 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.
YR 2019
FD 2019-11-11
LK https://hdl.handle.net/10668/25660
UL https://hdl.handle.net/10668/25660
LA en
DS RISalud
RD Apr 18, 2025