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Genome-wide association study of suicide attempt in psychiatric disorders identifies association with major depression polygenic risk scores

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

Posted 14 Sep 2018
bioRxiv DOI: 10.1101/416008

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 provide 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.

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