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. PenninxCarlos 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

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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
Issue number8
Publication statusPublished - 1 Jan 2019

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