Genome-wide association study of suicide attempt in psychiatric disorders identifies association with major depression polygenic risk scores
Authors: Mullins Niamh , Bigdeli Tim B. , Børglum Anders D , Coleman Jonathan R I , Demontis Ditte , Fanous Ayman H. , 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 , Świątkowska Beata , Baune Bernhard T , Müller-Myhsok Bertram , Konte Bettina , Penninx Brenda WJH , Pato Carlos , Zai Clement , Rujescu Dan , 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 , Giegling Ina , Agartz Ingrid , Melle Ingrid , Lawrence Jacob , Potash James B , Walters James TR , Strohmaier Jana , Shi Jianxin , Hauser Joanna , Biernacka Joanna M , Vincent John B , Kelsoe John , Strauss John S , Lissowska Jolanta , Pimm Jonathan , Smoller Jordan W , Parra José Guzman , Berger Klaus , Scott Laura J , Azevedo M. Helena , Trzaskowski Maciej , Kogevinas Manolis , Rietschel Marcella , Boks Marco , Ising Marcus , Grigoroiu-Serbanescu Maria , Hamshere Marian L , Leboyer Marion , Frye Mark , Nöthen Markus M , Alda Martin , Preisig Martin , Nordentoft Merete , Boehnke Michael , O’Donovan Michael C , Owen Michael J , Pato Michele T , Renteria Miguel , Budde Monika , Weissman Myrna M , Wray Naomi R , Bass Nicholas , Smeland Olav B , Andreassen Ole A , Mors Ole , Gejman Pablo V , Sklar Pamela , McGrath Patrick , Hoffmann Per , McGuffin Peter , Lee Phil H , Kahn René S , Ophoff Roel A , Adolfsson Rolf , Auwera Sandra Van der , Djurovic Srdjan , Shyn Stanley I , Kloiber Stefan , Heilmann-Heimbach Stefanie , Jamain Stéphane , Hamilton Steven P , McElroy Susan L , Lucae Susanne , Cichon Sven , Schulze Thomas G , Hansen Thomas , Werge Thomas , Air Tracy M , Nimgaonkar Vishwajit , Appadurai Vivek , Cahn Wiepke , 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, Kendler Kenneth S , McQuillin Andrew , Lewis Cathryn M 
Published: September 2018

Objective

Over 90% of suicide attempters have a psychiatric diagnosis, however twin and family studies suggest that the genetic etiology of suicide attempt (SA) is partially distinct from that of the psychiatric disorders themselves. Here, we present the largest genome-wide association study (GWAS) on suicide attempt using major depressive disorder (MDD), bipolar disorder (BIP) and schizophrenia (SCZ) cohorts from the Psychiatric Genomics Consortium.

Method

Samples comprise 1622 suicide attempters and 8786 non-attempters with MDD, 3264 attempters and 5500 non-attempters with BIP and 1683 attempters and 2946 non-attempters with SCZ. SA GWAS were performed comparing attempters to non-attempters in each disorder followed by meta-analysis across disorders. Polygenic risk scoring investigated the genetic relationship between SA and the psychiatric disorders.

Results

Three genome-wide significant loci for SA were found: one associated with SA in MDD, one in BIP, and one in the meta-analysis of SA in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. Polygenic risk scores for major depression were significantly associated with SA in MDD (P=0.0002), BIP (P=0.0006) and SCZ (P=0.0006).

Conclusions

This study provides new information on genetic associations and the genetic etiology of SA across psychiatric disorders. The finding that polygenic risk scores for major depression predict suicide attempt across disorders provides a possible starting point for predictive modelling and preventative strategies. Further collaborative efforts to increase sample size hold potential to robustly identify genetic associations and gain biological insights into the etiology of suicide attempt.