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

Research output: Contribution to journal › Journal article › Research › peer-review

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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; Stahl, Eli A.; Breen, Gerome; Forstner, Andreas J.; McQuillin, Andrew; Ripke, Stephan; Trubetskoy, Vassily; Mattheisen, Manuel; Wang, Yunpeng; Coleman, Jonathan R.I.; Gaspar, Héléna A.; de Leeuw, Christiaan A.; Steinberg, Stacy; Pers, Tune H.; Bækvad-Hansen, Marie; Pedersen, Carsten Bøcker; Pedersen, Marianne Giørtz; Hansen, Christine Søholm; Nordentoft, Merete; Werge, Thomas; Hansen, Thomas F.; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

In: Molecular Psychiatry, Vol. 26, No. 4, 2021, p. 1286-1298.

Research output: Contribution to journal › Journal article › Research › peer-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, Stahl, EA, Breen, G, Forstner, AJ, McQuillin, A, Ripke, S, Trubetskoy, V, Mattheisen, M, Wang, Y, Coleman, JRI, Gaspar, HA, de Leeuw, CA, Steinberg, S, Pers, TH, Bækvad-Hansen, M, Pedersen, CB, Pedersen, MG, Hansen, CS, Nordentoft, M, Werge, T, Hansen, TF, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium & Major Depressive 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., ... Major Depressive 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

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;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 ; Stahl, Eli A. ; Breen, Gerome ; Forstner, Andreas J. ; McQuillin, Andrew ; Ripke, Stephan ; Trubetskoy, Vassily ; Mattheisen, Manuel ; Wang, Yunpeng ; Coleman, Jonathan R.I. ; Gaspar, Héléna A. ; de Leeuw, Christiaan A. ; Steinberg, Stacy ; Pers, Tune H. ; Bækvad-Hansen, Marie ; Pedersen, Carsten Bøcker ; Pedersen, Marianne Giørtz ; Hansen, Christine Søholm ; Nordentoft, Merete ; Werge, Thomas ; Hansen, Thomas F. ; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium ; Major Depressive 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{c423e041a02d4e9ca7a13c8bca6fc26c,
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 Stahl, {Eli A.} and Gerome Breen and Forstner, {Andreas J.} and Andrew McQuillin and Stephan Ripke and Vassily Trubetskoy and Manuel Mattheisen and Yunpeng Wang and Coleman, {Jonathan R.I.} and Gaspar, {H{\'e}l{\'e}na A.} and {de Leeuw}, {Christiaan A.} and Stacy Steinberg and Pers, {Tune H.} and Marie B{\ae}kvad-Hansen and Pedersen, {Carsten B{\o}cker} and Pedersen, {Marianne Gi{\o}rtz} and Hansen, {Christine S{\o}holm} and Merete Nordentoft and Thomas Werge and Hansen, {Thomas F.} and {Bipolar Disorder Working Group of the Psychiatric Genomics Consortium} and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium}",
year = "2021",
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 - Stahl, Eli A.

AU - Breen, Gerome

AU - Forstner, Andreas J.

AU - McQuillin, Andrew

AU - Ripke, Stephan

AU - Trubetskoy, Vassily

AU - Mattheisen, Manuel

AU - Wang, Yunpeng

AU - Coleman, Jonathan R.I.

AU - Gaspar, Héléna A.

AU - de Leeuw, Christiaan A.

AU - Steinberg, Stacy

AU - Pers, Tune H.

AU - Bækvad-Hansen, Marie

AU - Pedersen, Carsten Bøcker

AU - Pedersen, Marianne Giørtz

AU - Hansen, Christine Søholm

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - Hansen, Thomas F.

AU - Bipolar Disorder Working Group of the Psychiatric Genomics Consortium

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

PY - 2021

Y1 - 2021

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

AN - SCOPUS:85075169356

VL - 26

SP - 1286

EP - 1298

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 4

ER -

ID: 260352032