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Meta-Analysis
. 2019 Aug 1;176(8):651-660.
doi: 10.1176/appi.ajp.2019.18080957. Epub 2019 Jun 5.

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

Niamh Mullins  1 , Tim B Bigdeli  1 , Anders D Børglum  1 , Jonathan R I Coleman  1 , Ditte Demontis  1 , Divya Mehta  1 , Robert A Power  1 , Stephan Ripke  1 , Eli A Stahl  1 , Anna Starnawska  1 , Adebayo Anjorin  1 ; M.R.C.Psych  1 ; Aiden Corvin  1 , Alan R Sanders  1 , Andreas J Forstner  1 , Andreas Reif  1 , Anna C Koller  1 , Beata Świątkowska  1 , Bernhard T Baune  1 , Bertram Müller-Myhsok  1 , Brenda W J H Penninx  1 , Carlos Pato  1 , Clement Zai  1 , Dan Rujescu  1 , David M Hougaard  1 , Digby Quested  1 , Douglas F Levinson  1 , Elisabeth B Binder  1 , Enda M Byrne  1 , Esben Agerbo  1 ; Dr.Med.Sc  1 ; Fabian Streit  1 , Fermin Mayoral  1 , Frank Bellivier  1 , Franziska Degenhardt  1 , Gerome Breen  1 , Gunnar Morken  1 , Gustavo Turecki  1 , Guy A Rouleau  1 , Hans J Grabe  1 , Henry Völzke  1 , Ian Jones  1 , Ina Giegling  1 , Ingrid Agartz  1 , Ingrid Melle  1 , Jacob Lawrence  1 ; M.R.C.Psych  1 ; James T R Walters  1 , Jana Strohmaier  1 , Jianxin Shi  1 , Joanna Hauser  1 , Joanna M Biernacka  1 , John B Vincent  1 , John Kelsoe  1 , John S Strauss  1 , Jolanta Lissowska  1 , Jonathan Pimm  1 ; M.R.C.Psych  1 ; Jordan W Smoller  1 , José Guzman-Parra  1 , Klaus Berger  1 , Laura J Scott  1 , Lisa A Jones  1 , M Helena Azevedo  1 , Maciej Trzaskowski  1 , Manolis Kogevinas  1 , Marcella Rietschel  1 , Marco Boks  1 , Marcus Ising  1 , Maria Grigoroiu-Serbanescu  1 , Marian L Hamshere  1 , Marion Leboyer  1 , Mark Frye  1 , Markus M Nöthen  1 , Martin Alda  1 , Martin Preisig  1 , Merete Nordentoft  1 , Michael Boehnke  1 , Michael C O'Donovan  1 , Michael J Owen  1 , Michele T Pato  1 , Miguel E Renteria  1 , Monika Budde  1 ; Dipl.-Psych  1 ; Myrna M Weissman  1 , Naomi R Wray  1 , Nicholas Bass  1 ; M.R.C.Psych  1 ; Nicholas Craddock  1 , Olav B Smeland  1 , Ole A Andreassen  1 , Ole Mors  1 , Pablo V Gejman  1 , Pamela Sklar  1 , Patrick McGrath  1 , Per Hoffmann  1 , Peter McGuffin  1 , Phil H Lee  1 , Preben Bo Mortensen  1 , René S Kahn  1 , Roel A Ophoff  1 , Rolf Adolfsson  1 , Sandra Van der Auwera  1 , Srdjan Djurovic  1 , Stefan Kloiber  1 , Stefanie Heilmann-Heimbach  1 , Stéphane Jamain  1 , Steven P Hamilton  1 , Susan L McElroy  1 , Susanne Lucae  1 , Sven Cichon  1 , Thomas G Schulze  1 , Thomas Hansen  1 , Thomas Werge  1 , Tracy M Air  1 , Vishwajit Nimgaonkar  1 , Vivek Appadurai  1 , Wiepke Cahn  1 , Yuri Milaneschi  1 ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium  1 ; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium  1 ; Schizophrenia Working Group of the Psychiatric Genomics Consortium  1 ; Ayman H Fanous  1 , Kenneth S Kendler  1 , Andrew McQuillin  1 , Cathryn M Lewis  1
Affiliations
Meta-Analysis

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

Niamh Mullins et al. Am J Psychiatry. .

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.

Keywords: Genome-Wide Association Study; Mood Disorders; Polygenic Risk Scoring; Psychiatric Genomics Consortium; Schizophrenia; Suicide.

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Conflict of interest statement

Disclosures

The authors declare no financial interests or potential conflicts of interest.

Figures

Figure 1:
Figure 1:. Manhattan plot for meta-analysis of suicide attempt in mood disorders.
The red line shows the genome-wide significance threshold (P < 5 × 10−8). SNPs in green are in linkage disequilibrium with the index SNPs (diamonds).
Figure 2:
Figure 2:. Polygenic risk scores for major depression are higher in suicide attempters versus non-attempters with bipolar disorder, major depressive disorder and schizophrenia.
The x-axis shows the P value threshold used to select SNPs from the discovery GWAS. The y-axis shows the percentage variance explained on the liability scale. P values of association between polygenic scores and suicide attempt are shown above each bar.
See this image and copyright information in PMC

Comment in

  • The Promise and Limits of Suicide Genetics.
    Lopes FL, McMahon FJ. Lopes FL, et al. Am J Psychiatry. 2019 Aug 1;176(8):600-602. doi: 10.1176/appi.ajp.2019.19060613. Am J Psychiatry. 2019. PMID: 31366231 No abstract available.

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