GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores

Mullins, Niamh and Bigdeli, Tim B and Børglum, Anders D and Coleman, Jonathan R I and Demontis, Ditte and Mehta, Divya and Power, Robert A and Ripke, Stephan and Stahl, Eli A and Starnawska, Anna and Anjorin, Adebayo and Corvin, Aiden and Sanders, Alan R and Forstner, Andreas J and Reif, Andreas and Koller, Anna C and Świątkowska, Beata and Baune, Bernhard T and Müller-Myhsok, Bertram and Penninx, Brenda W J H and Pato, Carlos and Zai, Clement and Rujescu, Dan and Hougaard, David M and Quested, Digby and Levinson, Douglas F and Binder, Elisabeth B and Byrne, Enda M and Agerbo, Esben and Streit, Fabian and Mayoral, Fermin and Bellivier, Frank and Degenhardt, Franziska and Breen, Gerome and Morken, Gunnar and Turecki, Gustavo and Rouleau, Guy A and Grabe, Hans J and Völzke, Henry and Jones, Ian and Giegling, Ina and Agartz, Ingrid and Melle, Ingrid and Lawrence, Jacob and Walters, James T R and Strohmaier, Jana and Shi, Jianxin and Hauser, Joanna and Biernacka, Joanna M and Jones, Lisa A and Knight, Jo (2019) GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores. American Journal of Psychiatry, 176 (8). pp. 651-660. ISSN 0002-953X

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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.

Item Type: Journal Article
Journal or Publication Title: American Journal of Psychiatry
Additional Information: © 2019 American Psychiatric Association The official published article is available online at https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2019.18080957
Uncontrolled Keywords: /dk/atira/pure/subjectarea/asjc/2700/2738
Subjects:
Departments: Faculty of Health and Medicine > Health Research
Faculty of Health and Medicine > Medicine
ID Code: 135894
Deposited By: ep_importer_pure
Deposited On: 31 Jul 2019 08:10
Refereed?: Yes
Published?: Published
Last Modified: 06 Dec 2019 04:52
URI: https://eprints.lancs.ac.uk/id/eprint/135894

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