Department of Economics and Business Economics

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

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Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders. / Andlauer, Till F M; Guzman-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; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium.

In: Molecular Psychiatry, Vol. 26, No. 4, 04.2021, p. 1286-1298.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

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, Rivas, F, Mayoral, F, Müller-Myhsok, B, Forstner, AJ, Nöthen, MM, Rietschel, M & Bipolar Disorder Working Group of the Psychiatric Genomics Consortium 2021, 'Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders', Molecular Psychiatry, vol. 26, no. 4, pp. 1286-1298. https://doi.org/10.1038/s41380-019-0558-2

APA

Andlauer, T. F. M., Guzman-Parra, J., Streit, F., Strohmaier, J., González, M. J., Gil Flores, S., Cabaleiro Fabeiro, F. J., Del Río Noriega, F., Perez, F. P., 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., ... Bipolar Disorder Working Group of the Psychiatric Genomics Consortium (2021). Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders. Molecular Psychiatry, 26(4), 1286-1298. https://doi.org/10.1038/s41380-019-0558-2

CBE

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, Rivas F, Mayoral F, Müller-Myhsok B, Forstner AJ, Nöthen MM, Rietschel M, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium. 2021. Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders. Molecular Psychiatry. 26(4):1286-1298. https://doi.org/10.1038/s41380-019-0558-2

MLA

Vancouver

Andlauer TFM, Guzman-Parra J, Streit F, Strohmaier J, González MJ, Gil Flores S et al. Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders. Molecular Psychiatry. 2021 Apr;26(4):1286-1298. https://doi.org/10.1038/s41380-019-0558-2

Author

Andlauer, Till F M ; Guzman-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 ; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium. / Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders. In: Molecular Psychiatry. 2021 ; Vol. 26, No. 4. pp. 1286-1298.

Bibtex

@article{a40df7ff003642259bcadb8afbeb206e,
title = "Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders",
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.",
author = "Andlauer, {Till F M} and Jose Guzman-Parra and Fabian Streit and Jana Strohmaier and Gonz{\'a}lez, {Maria Jos{\'e}} and {Gil Flores}, Susana and {Cabaleiro Fabeiro}, {Francisco J} and {Del R{\'i}o Noriega}, Francisco and Perez, {Fermin Perez} and {Haro Gonz{\'a}lez}, Jesus and {Orozco Diaz}, Guillermo and {de Diego-Otero}, Yolanda and Berta Moreno-K{\"u}stner and Georg Auburger and Franziska Degenhardt and Stefanie Heilmann-Heimbach and Stefan Herms and Per Hoffmann and Josef Frank and Foo, {Jerome C} and Jens Treutlein and Witt, {Stephanie H} and Sven Cichon and Manolis Kogevinas and Fabio Rivas and Ferm{\'i}n Mayoral and Bertram M{\"u}ller-Myhsok and Forstner, {Andreas J} and N{\"o}then, {Markus M} and Marcella Rietschel and {Bipolar Disorder Working Group of the Psychiatric Genomics Consortium} and Manuel Mattheisen and Als, {Thomas Damm} and Anders B{\o}rglum and Jakob Grove and Mortensen, {Preben Bo} and Esben Agerbo and Pedersen, {Marianne Gi{\o}rtz} and Pedersen, {Carsten B{\o}cker} and Christensen, {Jane Hvarregaard}",
year = "2021",
month = apr,
doi = "10.1038/s41380-019-0558-2",
language = "English",
volume = "26",
pages = "1286--1298",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "4",

}

RIS

TY - JOUR

T1 - Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

AU - Andlauer, Till F M

AU - Guzman-Parra, Jose

AU - Streit, Fabian

AU - Strohmaier, Jana

AU - González, Maria José

AU - Gil Flores, Susana

AU - Cabaleiro Fabeiro, Francisco J

AU - Del Río Noriega, Francisco

AU - Perez, Fermin Perez

AU - Haro González, Jesus

AU - Orozco Diaz, Guillermo

AU - de Diego-Otero, Yolanda

AU - Moreno-Küstner, Berta

AU - Auburger, Georg

AU - Degenhardt, Franziska

AU - Heilmann-Heimbach, Stefanie

AU - Herms, Stefan

AU - Hoffmann, Per

AU - Frank, Josef

AU - Foo, Jerome C

AU - Treutlein, Jens

AU - Witt, Stephanie H

AU - Cichon, Sven

AU - Kogevinas, Manolis

AU - Rivas, Fabio

AU - Mayoral, Fermín

AU - Müller-Myhsok, Bertram

AU - Forstner, Andreas J

AU - Nöthen, Markus M

AU - Rietschel, Marcella

AU - Bipolar Disorder Working Group of the Psychiatric Genomics Consortium

AU - Mattheisen, Manuel

AU - Als, Thomas Damm

AU - Børglum, Anders

AU - Grove, Jakob

AU - Mortensen, Preben Bo

AU - Agerbo, Esben

AU - Pedersen, Marianne Giørtz

AU - Pedersen, Carsten Bøcker

AU - Christensen, Jane Hvarregaard

PY - 2021/4

Y1 - 2021/4

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 (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.

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.

U2 - 10.1038/s41380-019-0558-2

DO - 10.1038/s41380-019-0558-2

M3 - Journal article

C2 - 31712721

VL - 26

SP - 1286

EP - 1298

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 4

ER -