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; 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.; Lewis, C.M.

Lists

Tools

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

Documents
Restricted Files
Details

[+][-]

Documents

7783:20324

[+][-]

7783:20324

[thumbnail of PGC_SuicideAttempt_GWAS_Mullins.pdf]

PGC_SuicideAttempt_GWAS_Mullins.pdf
Accepted Version Download (1MB)

Restricted Files

7783:18504

[+][-]

7783:18504

[thumbnail of PGC_SuicideAttempt_GWAS_Mullins.docx]

PGC_SuicideAttempt_GWAS_Mullins.docx
Download (2MB) Restricted to Repository staff only Request a copy

Details

Output Type:

Article

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.

Additional Information:

The full-text of the online published version cannot be supplied for this item. Please check availability with your local library or Interlibrary Requests Service.

Uncontrolled Discrete Keywords:

suicide attempt, psychiatric disorders, genome-wide association study, genetic association, genetic etiology

Subjects:

B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry

Legacy Divisions (Admin Only):

College of Health, Life and Environmental Sciences > School of Allied Health and Community

Academic Schools:

School of Health and Wellbeing

Related URLs:

Depositing User:

Katherine Gordon-Smith

Date Deposited: