TY  - INPR
A1  - Andlauer, Till
A1  - Guzman-Parra, José
A1  - Streit, Fabian
A1  - Strohmaier, Jana
A1  - González, Maria José
A1  - Flores, Susana Gil
A1  - Cabaleiro Fabeiro, Francisco J.
A1  - Rı́o Noriega, Francisco del
A1  - Perez, Fermin Perez
A1  - González, Jesus Haro
A1  - Orozco Diaz, Guillermo
A1  - de Diego-Otero, Yolanda
A1  - Moreno-Kuestner, Berta
A1  - Auburger, Georg
A1  - Degenhardt, Franziska
A1  - Heilmann-Heimbach, Stefanie
A1  - Herms, Stefan
A1  - Hoffmann, Per
A1  - Frank, Josef
A1  - Foo, Jerome Clifford
A1  - Treutlein, Jens
A1  - Witt, Stephanie H.
A1  - Cichon, Sven
A1  - Kogevinas, Manolis
A1  - Rivas, Fabio
A1  - Mayoral, Fermı́n
A1  - Müller-Myhsok, Bertram
A1  - Forstner, Andreas Josef
A1  - Nöthen, Markus Maria
A1  - Rietschel, Marcella
T1  - Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders
T2  - bioRxiv
N2  - 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 as well as 438 subjects from an independent, sporadic BD case-control cohort were analysed. Polygenic risk scores (PRS) for BD, schizophrenia, and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had significantly higher PRS for all three psychiatric disorders than the independent controls, 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 sporadic 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, therefore, 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. The PRS explained only part of the observed phenotypic variance and rare variants might have also contributed to disease development.
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73221
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-732218
N1  - Preprint, später in Molecular Psychiatry doi: 10.1038/s41380-019-0558-2
IS  - 468975
ER  -