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Genetic Relationships Between Suicide Attempts, Suicidal Ideation and Major Psychiatric Disorders: a Genome-wide Association and Polygenic Scoring Study

Mullins, N. and Perroud, N. and Uher, R. and Butler, A.W. and Cohen-Woods, S. and Rivera, M. and Malki, K. and Eusden, J. and Power, R.A. and Tansey, K.E. and Jones, Lisa and Jones, I. and Craddock, N. and Owen, M.J. and Korszun, A. and Gill, M. and Mors, O. and Priesig, M. and Maier, W. and Rietschel, M. and Rice, J.P. and Müller-Myhsok, B. and Lucae, S. and Binder, E.B. and Ising, M. and Craig, I.W. and Farmer, A.E. and McGuffin, P. and Breen, G. and Lewis, C.M. (2014) Genetic Relationships Between Suicide Attempts, Suicidal Ideation and Major Psychiatric Disorders: a Genome-wide Association and Polygenic Scoring Study. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 165 (5). pp. 428-437. ISSN Online: 1552-485X

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Abstract

Epidemiological studies have recognized a genetic diathesis for suicidal behavior, which is independent of other psychiatric disorders. Genome-wide association studies (GWAS) on suicide attempt (SA) and ideation have failed to identify specific genetic variants. Here, we conduct further GWAS and for the first time, use polygenic score analysis in cohorts of patients with mood disorders, to test for common genetic variants for mood disorders and suicide phenotypes. Genome-wide studies for SA were conducted in the RADIANT and GSK-Munich recurrent depression samples and London Bipolar Affective Disorder Case-Control Study (BACCs) then meta-analysis was performed. A GWAS on suicidal ideation during antidepressant treatment had previously been conducted in the Genome Based Therapeutic Drugs for Depression (GENDEP) study. We derived polygenic scores from each sample and tested their ability to predict SA in the mood disorder cohorts or ideation status in the GENDEP study. Polygenic scores for major depressive disorder, bipolar disorder and schizophrenia from the Psychiatric Genomics Consortium were used to investigate pleiotropy between psychiatric disorders and suicide phenotypes. No significant evidence for association was detected at any SNP in GWAS or meta-analysis. Polygenic scores for major depressive disorder significantly predicted suicidal ideation in the GENDEP pharmacogenetics study and also predicted SA in a combined validation dataset. Polygenic scores for SA showed no predictive ability for suicidal ideation. Polygenic score analysis suggests pleiotropy between psychiatric disorders and suicidal ideation whereas the tendency to act on such thoughts may have a partially independent genetic diathesis.

Item Type: Article
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Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Academic Departments > Institute of Health and Society
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Copyright Info: Open Access journal article
Depositing User: Lisa Jones
Date Deposited: 16 Jan 2017 12:21
Last Modified: 16 Jan 2017 12:31
URI: https://eprints.worc.ac.uk/id/eprint/5236

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