GWAS of suicide attempt in psychiatric disorders and association with major depression polygenic risk scores

Niamh Mullins, Tim B. Bigdeli, Anders D. Børglum, Jonathan R. I. Coleman, Ditte Demontis, Divya Mehta, Robert A. Power, Stephan Ripke, Eli A. Stahl, Anna Starnawska, Adebayo Anjorin, Aiden Corvin, Alan R. Sanders, Andreas J. Forstner, Andreas Reif, Anna C. Koller, Beata Swia Tkowska, Bernhard T. Baune, Bertram Müller-Myhsok, Brenda W. J. H. Penninx & 35 others Carlos Pato, Clement Zai, Dan Rujescu, David M. Hougaard, Digby Quested, Douglas F. Levinson, Elisabeth B. Binder, Enda M. Byrne, Esben Agerbo, Fabian Streit, Fermin Mayoral, Frank Bellivier, Franziska Degenhardt, Gerome Breen, Gunnar Morken, Gustavo Turecki, Guy A. Rouleau, Hans J. Grabe, Henry Völzke, Ian Jones, Ina Giegling, Ingrid Agartz, Ingrid Melle, Jacob Lawrence, James T. R. Walters, Jana Strohmaier, Jianxin Shi, Joanna Hauser, Joanna M. Biernacka, Yuri Milaneschi, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Ayman H. Fanous, Kenneth S. Kendler, Andrew McQuillin, Cathryn M. Lewis

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objective: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium. Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders. Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2= 0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2= 0.40%). Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.
Original languageEnglish
Pages (from-to)651-660
JournalAmerican Journal of Psychiatry
Volume176
Issue number8
DOIs
Publication statusPublished - 1 Jan 2019

Cite this

Mullins, N., Bigdeli, T. B., Børglum, A. D., Coleman, J. R. I., Demontis, D., Mehta, D., ... Lewis, C. M. (2019). GWAS of suicide attempt in psychiatric disorders and association with major depression polygenic risk scores. American Journal of Psychiatry, 176(8), 651-660. https://doi.org/10.1176/appi.ajp.2019.18080957
Mullins, Niamh ; Bigdeli, Tim B. ; Børglum, Anders D. ; Coleman, Jonathan R. I. ; Demontis, Ditte ; Mehta, Divya ; Power, Robert A. ; Ripke, Stephan ; Stahl, Eli A. ; Starnawska, Anna ; Anjorin, Adebayo ; Corvin, Aiden ; Sanders, Alan R. ; Forstner, Andreas J. ; Reif, Andreas ; Koller, Anna C. ; Tkowska, Beata Swia ; Baune, Bernhard T. ; Müller-Myhsok, Bertram ; Penninx, Brenda W. J. H. ; Pato, Carlos ; Zai, Clement ; Rujescu, Dan ; Hougaard, David M. ; Quested, Digby ; Levinson, Douglas F. ; Binder, Elisabeth B. ; Byrne, Enda M. ; Agerbo, Esben ; Streit, Fabian ; Mayoral, Fermin ; Bellivier, Frank ; Degenhardt, Franziska ; Breen, Gerome ; Morken, Gunnar ; Turecki, Gustavo ; Rouleau, Guy A. ; Grabe, Hans J. ; Völzke, Henry ; Jones, Ian ; Giegling, Ina ; Agartz, Ingrid ; Melle, Ingrid ; Lawrence, Jacob ; Walters, James T. R. ; Strohmaier, Jana ; Shi, Jianxin ; Hauser, Joanna ; Biernacka, Joanna M. ; Milaneschi, Yuri ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium ; Fanous, Ayman H. ; Kendler, Kenneth S. ; McQuillin, Andrew ; Lewis, Cathryn M. / GWAS of suicide attempt in psychiatric disorders and association with major depression polygenic risk scores. In: American Journal of Psychiatry. 2019 ; Vol. 176, No. 8. pp. 651-660.
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title = "GWAS of suicide attempt in psychiatric disorders and association with major depression polygenic risk scores",
abstract = "Objective: More than 90{\%} of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium. Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders. Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2= 0.25{\%}), bipolar disorder (R2=0.24{\%}), and schizophrenia (R2= 0.40{\%}). Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.",
author = "Niamh Mullins and Bigdeli, {Tim B.} and B{\o}rglum, {Anders D.} and Coleman, {Jonathan R. I.} and Ditte Demontis and Divya Mehta and Power, {Robert A.} and Stephan Ripke and Stahl, {Eli A.} and Anna Starnawska and Adebayo Anjorin and Aiden Corvin and Sanders, {Alan R.} and Forstner, {Andreas J.} and Andreas Reif and Koller, {Anna C.} and Tkowska, {Beata Swia} and Baune, {Bernhard T.} and Bertram M{\"u}ller-Myhsok and Penninx, {Brenda W. J. H.} and Carlos Pato and Clement Zai and Dan Rujescu and Hougaard, {David M.} and Digby Quested and Levinson, {Douglas F.} and Binder, {Elisabeth B.} and Byrne, {Enda M.} and Esben Agerbo and Fabian Streit and Fermin Mayoral and Frank Bellivier and Franziska Degenhardt and Gerome Breen and Gunnar Morken and Gustavo Turecki and Rouleau, {Guy A.} and Grabe, {Hans J.} and Henry V{\"o}lzke and Ian Jones and Ina Giegling and Ingrid Agartz and Ingrid Melle and Jacob Lawrence and Walters, {James T. R.} and Jana Strohmaier and Jianxin Shi and Joanna Hauser and Biernacka, {Joanna M.} and Yuri Milaneschi and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium} and Fanous, {Ayman H.} and Kendler, {Kenneth S.} and Andrew McQuillin and Lewis, {Cathryn M.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1176/appi.ajp.2019.18080957",
language = "English",
volume = "176",
pages = "651--660",
journal = "American Journal of Psychiatry",
issn = "0002-953X",
publisher = "American Psychiatric Association",
number = "8",

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Mullins, N, Bigdeli, TB, Børglum, AD, Coleman, JRI, Demontis, D, Mehta, D, Power, RA, Ripke, S, Stahl, EA, Starnawska, A, Anjorin, A, Corvin, A, Sanders, AR, Forstner, AJ, Reif, A, Koller, AC, Tkowska, BS, Baune, BT, Müller-Myhsok, B, Penninx, BWJH, Pato, C, Zai, C, Rujescu, D, Hougaard, DM, Quested, D, Levinson, DF, Binder, EB, Byrne, EM, Agerbo, E, Streit, F, Mayoral, F, Bellivier, F, Degenhardt, F, Breen, G, Morken, G, Turecki, G, Rouleau, GA, Grabe, HJ, Völzke, H, Jones, I, Giegling, I, Agartz, I, Melle, I, Lawrence, J, Walters, JTR, Strohmaier, J, Shi, J, Hauser, J, Biernacka, JM, Milaneschi, Y, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Fanous, AH, Kendler, KS, McQuillin, A & Lewis, CM 2019, 'GWAS of suicide attempt in psychiatric disorders and association with major depression polygenic risk scores' American Journal of Psychiatry, vol. 176, no. 8, pp. 651-660. https://doi.org/10.1176/appi.ajp.2019.18080957

GWAS of suicide attempt in psychiatric disorders and association with major depression polygenic risk scores. / Mullins, Niamh; Bigdeli, Tim B.; Børglum, Anders D.; Coleman, Jonathan R. I.; Demontis, Ditte; Mehta, Divya; Power, Robert A.; Ripke, Stephan; Stahl, Eli A.; Starnawska, Anna; Anjorin, Adebayo; Corvin, Aiden; Sanders, Alan R.; Forstner, Andreas J.; Reif, Andreas; Koller, Anna C.; Tkowska, Beata Swia; Baune, Bernhard T.; Müller-Myhsok, Bertram; Penninx, Brenda W. J. H.; Pato, Carlos; Zai, Clement; Rujescu, Dan; Hougaard, David M.; Quested, Digby; Levinson, Douglas F.; Binder, Elisabeth B.; Byrne, Enda M.; Agerbo, Esben; Streit, Fabian; Mayoral, Fermin; Bellivier, Frank; Degenhardt, Franziska; Breen, Gerome; Morken, Gunnar; Turecki, Gustavo; Rouleau, Guy A.; Grabe, Hans J.; Völzke, Henry; Jones, Ian; Giegling, Ina; Agartz, Ingrid; Melle, Ingrid; Lawrence, Jacob; Walters, James T. R.; Strohmaier, Jana; Shi, Jianxin; Hauser, Joanna; Biernacka, Joanna M.; Milaneschi, Yuri; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium; Fanous, Ayman H.; Kendler, Kenneth S.; McQuillin, Andrew; Lewis, Cathryn M.

In: American Journal of Psychiatry, Vol. 176, No. 8, 01.01.2019, p. 651-660.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - GWAS of suicide attempt in psychiatric disorders and association with major depression polygenic risk scores

AU - Mullins, Niamh

AU - Bigdeli, Tim B.

AU - Børglum, Anders D.

AU - Coleman, Jonathan R. I.

AU - Demontis, Ditte

AU - Mehta, Divya

AU - Power, Robert A.

AU - Ripke, Stephan

AU - Stahl, Eli A.

AU - Starnawska, Anna

AU - Anjorin, Adebayo

AU - Corvin, Aiden

AU - Sanders, Alan R.

AU - Forstner, Andreas J.

AU - Reif, Andreas

AU - Koller, Anna C.

AU - Tkowska, Beata Swia

AU - Baune, Bernhard T.

AU - Müller-Myhsok, Bertram

AU - Penninx, Brenda W. J. H.

AU - Pato, Carlos

AU - Zai, Clement

AU - Rujescu, Dan

AU - Hougaard, David M.

AU - Quested, Digby

AU - Levinson, Douglas F.

AU - Binder, Elisabeth B.

AU - Byrne, Enda M.

AU - Agerbo, Esben

AU - Streit, Fabian

AU - Mayoral, Fermin

AU - Bellivier, Frank

AU - Degenhardt, Franziska

AU - Breen, Gerome

AU - Morken, Gunnar

AU - Turecki, Gustavo

AU - Rouleau, Guy A.

AU - Grabe, Hans J.

AU - Völzke, Henry

AU - Jones, Ian

AU - Giegling, Ina

AU - Agartz, Ingrid

AU - Melle, Ingrid

AU - Lawrence, Jacob

AU - Walters, James T. R.

AU - Strohmaier, Jana

AU - Shi, Jianxin

AU - Hauser, Joanna

AU - Biernacka, Joanna M.

AU - Milaneschi, Yuri

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

AU - Fanous, Ayman H.

AU - Kendler, Kenneth S.

AU - McQuillin, Andrew

AU - Lewis, Cathryn M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium. Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders. Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2= 0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2= 0.40%). Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.

AB - Objective: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium. Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders. Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2= 0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2= 0.40%). Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85070289870&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/31164008

U2 - 10.1176/appi.ajp.2019.18080957

DO - 10.1176/appi.ajp.2019.18080957

M3 - Article

VL - 176

SP - 651

EP - 660

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

SN - 0002-953X

IS - 8

ER -