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

Mullins, N., Bigdeli, T.B., Børglum, A.D., Coleman, J.R.I., Demontis, D., Mehta, D., Power, R.A., Ripke, S., Stahl, E.A., Starnawska, A., Anjorin, A., Corvin, A., Sanders, A.R., Forstner, A.J., Reif, A., Koller, A.C., Świątkowska, B., Baune, B.T., Müller-Myhsok, B., Konte, B., Penninx, B.W.J.H., Pato, C., Zai, C., Rujescu, D., Hougaard, D.M., Quested, D., Levinson, D.F., Binder, E.B., Byrne, E.M., Agerbo, E., Streit, F., Mayoral, F., Bellivier, F., Dehenhardt, F., Breen, G., Morken, G., Turecki, G., Rouleau, G.A., Grabe, H.J., Völzke, H., Jones, I., Giegling, I., Agartz, I., Melle, I., Lawrence, J., Potash, J.B., Walters, J.T.R., Strohmaier, J., Shi, J., Hauser, J., Biernacka, J.M., Vincent, J.B., Kelsoe, J., Strauss, J.S., Lissowska, J., Pimm, J.W., Smoller, J., Parra, J.G., Berger, K., Scott, L.J., Jones, Lisa ORCID: https://orcid.org/0000-0002-5122-8334, Azevedo, M.H., Trzaskowski, M., Kogevinas, M., Rietschel, M., Boks, M., Ising, M., Grigoroiu-Serbanescu, M., Hamshere, M.L., Leboyer, M., Frye, M., Nöthen, M.M., Alda, M., Preisig, M., Nordentoft, M., Boehnke, M., O'Donovan, M.C., Owen, M.J., Pato, M.T., Renteria, M., Budde, M., Weissman, M.M., Wray, N.R., Bass, N., Craddock, N., Smeland, O.B., Andreassen, O.A., Mors, O., Gejman, P.V., Sklar, P., McGrath, P., Hoffman, P., McGuffin, P., Lee, P.H., Mortensen, P.B., Kahn, R.S., Ophoff, R.A., Adolfsson, R., Van der Auwera, S., Djurovic, S., Shyn, S.I., Kloiber, S., Heilmann-Heimbach, S., Jamain, S., Hamilton, S.P., McElroy, S.L., Lucae, S., Cichon, S., Schulze, T.G., Hansen, T., Werge, T., Air, T.M., Nimgaonkar, V., Appadurai, V., Cahn, W., Milaneschi, Y., Kendler, K.S., Fanous, A.H., McQuillin, A. and Lewis, C.M. (2019) GWAS of Suicide Attempt in Psychiatric Disorders Identifies Association With Major Depression Polygenic Risk Scores. The American Journal of Psychiatry, 176 (8). pp. 651-660. ISSN Print: 0002-953X Online: 1535-7228

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Abstract

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 by comparing attempters to non-attempters in each disorder followed by meta-analyses across disorders. Polygenic risk scoring was used to investigate 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. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with SA in MDD (R2=0.25%, P=0.0006), BIP (R2=0.24%, P=0.0002) and SCZ (R2=0.40%, P=0.0006).

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 hold potential to robustly identify genetic associations and gain biological insights into the etiology of suicide attempt.

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