The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls

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The Genetics of the Mood Disorder Spectrum : Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls. / Coleman, Jonathan R.I.; Gaspar, Héléna A.; Bryois, Julien; Byrne, Enda M.; Forstner, Andreas J.; Holmans, Peter A.; de Leeuw, Christiaan A.; Mattheisen, Manuel; McQuillin, Andrew; Whitehead Pavlides, Jennifer M.; Pers, Tune H.; Ripke, Stephan; Stahl, Eli A.; Steinberg, Stacy; Trubetskoy, Vassily; Trzaskowski, Maciej; Wang, Yunpeng; Abbott, Liam; Abdellaoui, Abdel; Adams, Mark J.; Adolfsson, Annelie Nordin; Agerbo, Esben; Akil, Huda; Albani, Diego; Alliey-Rodriguez, Ney; Als, Thomas D.; Andlauer, Till F.M.; Anjorin, Adebayo; Antilla, Verneri; Van der Auwera, Sandra; Awasthi, Swapnil; Bacanu, Silviu Alin; Badner, Judith A.; Bækvad-Hansen, Marie; Barchas, Jack D.; Bass, Nicholas; Bauer, Michael; Beekman, Aartjan T.F.; Belliveau, Richard; Bergen, Sarah E.; Bigdeli, Tim B.; Binder, Elisabeth B.; Bøen, Erlend; Hansen, Christine Søholm; Hansen, Thomas F.; Krogh, Jesper; Pedersen, Carsten Bøcker; Pedersen, Marianne Giørtz; Nordentoft, Merete; Werge, Thomas; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

In: Biological Psychiatry, Vol. 88, No. 2, 2020, p. 169-184.

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

Harvard

Coleman, JRI, Gaspar, HA, Bryois, J, Byrne, EM, Forstner, AJ, Holmans, PA, de Leeuw, CA, Mattheisen, M, McQuillin, A, Whitehead Pavlides, JM, Pers, TH, Ripke, S, Stahl, EA, Steinberg, S, Trubetskoy, V, Trzaskowski, M, Wang, Y, Abbott, L, Abdellaoui, A, Adams, MJ, Adolfsson, AN, Agerbo, E, Akil, H, Albani, D, Alliey-Rodriguez, N, Als, TD, Andlauer, TFM, Anjorin, A, Antilla, V, Van der Auwera, S, Awasthi, S, Bacanu, SA, Badner, JA, Bækvad-Hansen, M, Barchas, JD, Bass, N, Bauer, M, Beekman, ATF, Belliveau, R, Bergen, SE, Bigdeli, TB, Binder, EB, Bøen, E, Hansen, CS, Hansen, TF, Krogh, J, Pedersen, CB, Pedersen, MG, Nordentoft, M, Werge, T, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2020, 'The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls', Biological Psychiatry, vol. 88, no. 2, pp. 169-184. https://doi.org/10.1016/j.biopsych.2019.10.015

APA

Coleman, J. R. I., Gaspar, H. A., Bryois, J., Byrne, E. M., Forstner, A. J., Holmans, P. A., de Leeuw, C. A., Mattheisen, M., McQuillin, A., Whitehead Pavlides, J. M., Pers, T. H., Ripke, S., Stahl, E. A., Steinberg, S., Trubetskoy, V., Trzaskowski, M., Wang, Y., Abbott, L., Abdellaoui, A., ... Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2020). The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls. Biological Psychiatry, 88(2), 169-184. https://doi.org/10.1016/j.biopsych.2019.10.015

Vancouver

Coleman JRI, Gaspar HA, Bryois J, Byrne EM, Forstner AJ, Holmans PA et al. The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls. Biological Psychiatry. 2020;88(2):169-184. https://doi.org/10.1016/j.biopsych.2019.10.015

Author

Coleman, Jonathan R.I. ; Gaspar, Héléna A. ; Bryois, Julien ; Byrne, Enda M. ; Forstner, Andreas J. ; Holmans, Peter A. ; de Leeuw, Christiaan A. ; Mattheisen, Manuel ; McQuillin, Andrew ; Whitehead Pavlides, Jennifer M. ; Pers, Tune H. ; Ripke, Stephan ; Stahl, Eli A. ; Steinberg, Stacy ; Trubetskoy, Vassily ; Trzaskowski, Maciej ; Wang, Yunpeng ; Abbott, Liam ; Abdellaoui, Abdel ; Adams, Mark J. ; Adolfsson, Annelie Nordin ; Agerbo, Esben ; Akil, Huda ; Albani, Diego ; Alliey-Rodriguez, Ney ; Als, Thomas D. ; Andlauer, Till F.M. ; Anjorin, Adebayo ; Antilla, Verneri ; Van der Auwera, Sandra ; Awasthi, Swapnil ; Bacanu, Silviu Alin ; Badner, Judith A. ; Bækvad-Hansen, Marie ; Barchas, Jack D. ; Bass, Nicholas ; Bauer, Michael ; Beekman, Aartjan T.F. ; Belliveau, Richard ; Bergen, Sarah E. ; Bigdeli, Tim B. ; Binder, Elisabeth B. ; Bøen, Erlend ; Hansen, Christine Søholm ; Hansen, Thomas F. ; Krogh, Jesper ; Pedersen, Carsten Bøcker ; Pedersen, Marianne Giørtz ; Nordentoft, Merete ; Werge, Thomas ; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. / The Genetics of the Mood Disorder Spectrum : Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls. In: Biological Psychiatry. 2020 ; Vol. 88, No. 2. pp. 169-184.

Bibtex

@article{e4248c9e0b1b4185af2ed51a541f3f4d,
title = "The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls",
abstract = "Background: Mood disorders (including major depressive disorder and bipolar disorder) affect 10% to 20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of risk factors across mood disorders despite their diagnostic distinction. Methods: To clarify the shared molecular genetic basis of major depressive disorder and bipolar disorder and to highlight disorder-specific associations, we meta-analyzed data from the latest Psychiatric Genomics Consortium genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; nonoverlapping N = 609,424). Results: Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More loci from the Psychiatric Genomics Consortium analysis of major depression than from that for bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single-episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment—the relationship is positive in bipolar disorder but negative in major depressive disorder. Conclusions: The mood disorders share several genetic associations, and genetic studies of major depressive disorder and bipolar disorder can be combined effectively to enable the discovery of variants not identified by studying either disorder alone. However, we demonstrate several differences between these disorders. Analyzing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum.",
keywords = "Affective disorders, Bipolar disorder, Genetic correlation, Genome-wide association study, Major depressive disorder, Mood disorders",
author = "Coleman, {Jonathan R.I.} and Gaspar, {H{\'e}l{\'e}na A.} and Julien Bryois and Byrne, {Enda M.} and Forstner, {Andreas J.} and Holmans, {Peter A.} and {de Leeuw}, {Christiaan A.} and Manuel Mattheisen and Andrew McQuillin and {Whitehead Pavlides}, {Jennifer M.} and Pers, {Tune H.} and Stephan Ripke and Stahl, {Eli A.} and Stacy Steinberg and Vassily Trubetskoy and Maciej Trzaskowski and Yunpeng Wang and Liam Abbott and Abdel Abdellaoui and Adams, {Mark J.} and Adolfsson, {Annelie Nordin} and Esben Agerbo and Huda Akil and Diego Albani and Ney Alliey-Rodriguez and Als, {Thomas D.} and Andlauer, {Till F.M.} and Adebayo Anjorin and Verneri Antilla and {Van der Auwera}, Sandra and Swapnil Awasthi and Bacanu, {Silviu Alin} and Badner, {Judith A.} and Marie B{\ae}kvad-Hansen and Barchas, {Jack D.} and Nicholas Bass and Michael Bauer and Beekman, {Aartjan T.F.} and Richard Belliveau and Bergen, {Sarah E.} and Bigdeli, {Tim B.} and Binder, {Elisabeth B.} and Erlend B{\o}en and Hansen, {Christine S{\o}holm} and Hansen, {Thomas F.} and Jesper Krogh and Pedersen, {Carsten B{\o}cker} and Pedersen, {Marianne Gi{\o}rtz} and Merete Nordentoft and Thomas Werge and {Bipolar Disorder Working Group of the Psychiatric Genomics Consortium} and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium}",
year = "2020",
doi = "10.1016/j.biopsych.2019.10.015",
language = "English",
volume = "88",
pages = "169--184",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier",
number = "2",

}

RIS

TY - JOUR

T1 - The Genetics of the Mood Disorder Spectrum

T2 - Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls

AU - Coleman, Jonathan R.I.

AU - Gaspar, Héléna A.

AU - Bryois, Julien

AU - Byrne, Enda M.

AU - Forstner, Andreas J.

AU - Holmans, Peter A.

AU - de Leeuw, Christiaan A.

AU - Mattheisen, Manuel

AU - McQuillin, Andrew

AU - Whitehead Pavlides, Jennifer M.

AU - Pers, Tune H.

AU - Ripke, Stephan

AU - Stahl, Eli A.

AU - Steinberg, Stacy

AU - Trubetskoy, Vassily

AU - Trzaskowski, Maciej

AU - Wang, Yunpeng

AU - Abbott, Liam

AU - Abdellaoui, Abdel

AU - Adams, Mark J.

AU - Adolfsson, Annelie Nordin

AU - Agerbo, Esben

AU - Akil, Huda

AU - Albani, Diego

AU - Alliey-Rodriguez, Ney

AU - Als, Thomas D.

AU - Andlauer, Till F.M.

AU - Anjorin, Adebayo

AU - Antilla, Verneri

AU - Van der Auwera, Sandra

AU - Awasthi, Swapnil

AU - Bacanu, Silviu Alin

AU - Badner, Judith A.

AU - Bækvad-Hansen, Marie

AU - Barchas, Jack D.

AU - Bass, Nicholas

AU - Bauer, Michael

AU - Beekman, Aartjan T.F.

AU - Belliveau, Richard

AU - Bergen, Sarah E.

AU - Bigdeli, Tim B.

AU - Binder, Elisabeth B.

AU - Bøen, Erlend

AU - Hansen, Christine Søholm

AU - Hansen, Thomas F.

AU - Krogh, Jesper

AU - Pedersen, Carsten Bøcker

AU - Pedersen, Marianne Giørtz

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - Bipolar Disorder Working Group of the Psychiatric Genomics Consortium

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

PY - 2020

Y1 - 2020

N2 - Background: Mood disorders (including major depressive disorder and bipolar disorder) affect 10% to 20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of risk factors across mood disorders despite their diagnostic distinction. Methods: To clarify the shared molecular genetic basis of major depressive disorder and bipolar disorder and to highlight disorder-specific associations, we meta-analyzed data from the latest Psychiatric Genomics Consortium genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; nonoverlapping N = 609,424). Results: Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More loci from the Psychiatric Genomics Consortium analysis of major depression than from that for bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single-episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment—the relationship is positive in bipolar disorder but negative in major depressive disorder. Conclusions: The mood disorders share several genetic associations, and genetic studies of major depressive disorder and bipolar disorder can be combined effectively to enable the discovery of variants not identified by studying either disorder alone. However, we demonstrate several differences between these disorders. Analyzing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum.

AB - Background: Mood disorders (including major depressive disorder and bipolar disorder) affect 10% to 20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of risk factors across mood disorders despite their diagnostic distinction. Methods: To clarify the shared molecular genetic basis of major depressive disorder and bipolar disorder and to highlight disorder-specific associations, we meta-analyzed data from the latest Psychiatric Genomics Consortium genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; nonoverlapping N = 609,424). Results: Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More loci from the Psychiatric Genomics Consortium analysis of major depression than from that for bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single-episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment—the relationship is positive in bipolar disorder but negative in major depressive disorder. Conclusions: The mood disorders share several genetic associations, and genetic studies of major depressive disorder and bipolar disorder can be combined effectively to enable the discovery of variants not identified by studying either disorder alone. However, we demonstrate several differences between these disorders. Analyzing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum.

KW - Affective disorders

KW - Bipolar disorder

KW - Genetic correlation

KW - Genome-wide association study

KW - Major depressive disorder

KW - Mood disorders

U2 - 10.1016/j.biopsych.2019.10.015

DO - 10.1016/j.biopsych.2019.10.015

M3 - Journal article

C2 - 31926635

AN - SCOPUS:85078024661

VL - 88

SP - 169

EP - 184

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 2

ER -

ID: 259052709