Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome-wide association and polygenic scoring study

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...

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Main Authors:	Mullins, Niamh, Perroud, Nader, Uher, Rudolf, Butler, Amy W, Cohen-Woods, Sarah, Rivera, Margarita, Malki, Karim, Euesden, Jack, Power, Robert A, Tansey, Katherine E, Jones, Lisa, Jones, Ian, Craddock, Nick, Owen, Michael J, Korszun, Ania, Gill, Michael, Mors, Ole, Preisig, Martin, Maier, Wolfgang, Rietschel, Marcella, Rice, John P, Müller-Myhsok, Bertram, Binder, Elisabeth B, Lucae, Susanne, Ising, Marcus, Craig, Ian W, Farmer, Anne E, McGuffin, Peter, Breen, Gerome, Lewis, Cathryn M
Format:	Online
Language:	English
Published:	BlackWell Publishing Ltd 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309466/

id	pubmed-4309466
recordtype	oai_dc
spelling	pubmed-43094662015-02-09 Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome-wide association and polygenic scoring study Mullins, Niamh Perroud, Nader Uher, Rudolf Butler, Amy W Cohen-Woods, Sarah Rivera, Margarita Malki, Karim Euesden, Jack Power, Robert A Tansey, Katherine E Jones, Lisa Jones, Ian Craddock, Nick Owen, Michael J Korszun, Ania Gill, Michael Mors, Ole Preisig, Martin Maier, Wolfgang Rietschel, Marcella Rice, John P Müller-Myhsok, Bertram Binder, Elisabeth B Lucae, Susanne Ising, Marcus Craig, Ian W Farmer, Anne E McGuffin, Peter Breen, Gerome Lewis, Cathryn M Research Articles 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. © 2014 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals, Inc. BlackWell Publishing Ltd 2014-07 2014-06-25 /pmc/articles/PMC4309466/ /pubmed/24964207 http://dx.doi.org/10.1002/ajmg.b.32247 Text en © 2014 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals, Inc. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Mullins, Niamh Perroud, Nader Uher, Rudolf Butler, Amy W Cohen-Woods, Sarah Rivera, Margarita Malki, Karim Euesden, Jack Power, Robert A Tansey, Katherine E Jones, Lisa Jones, Ian Craddock, Nick Owen, Michael J Korszun, Ania Gill, Michael Mors, Ole Preisig, Martin Maier, Wolfgang Rietschel, Marcella Rice, John P Müller-Myhsok, Bertram Binder, Elisabeth B Lucae, Susanne Ising, Marcus Craig, Ian W Farmer, Anne E McGuffin, Peter Breen, Gerome Lewis, Cathryn M
spellingShingle	Mullins, Niamh Perroud, Nader Uher, Rudolf Butler, Amy W Cohen-Woods, Sarah Rivera, Margarita Malki, Karim Euesden, Jack Power, Robert A Tansey, Katherine E Jones, Lisa Jones, Ian Craddock, Nick Owen, Michael J Korszun, Ania Gill, Michael Mors, Ole Preisig, Martin Maier, Wolfgang Rietschel, Marcella Rice, John P Müller-Myhsok, Bertram Binder, Elisabeth B Lucae, Susanne Ising, Marcus Craig, Ian W Farmer, Anne E McGuffin, Peter Breen, Gerome Lewis, Cathryn M Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome-wide association and polygenic scoring study
author_facet	Mullins, Niamh Perroud, Nader Uher, Rudolf Butler, Amy W Cohen-Woods, Sarah Rivera, Margarita Malki, Karim Euesden, Jack Power, Robert A Tansey, Katherine E Jones, Lisa Jones, Ian Craddock, Nick Owen, Michael J Korszun, Ania Gill, Michael Mors, Ole Preisig, Martin Maier, Wolfgang Rietschel, Marcella Rice, John P Müller-Myhsok, Bertram Binder, Elisabeth B Lucae, Susanne Ising, Marcus Craig, Ian W Farmer, Anne E McGuffin, Peter Breen, Gerome Lewis, Cathryn M
author_sort	Mullins, Niamh
title	Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome-wide association and polygenic scoring study
title_short	Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome-wide association and polygenic scoring study
title_full	Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome-wide association and polygenic scoring study
title_fullStr	Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome-wide association and polygenic scoring study
title_full_unstemmed	Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome-wide association and polygenic scoring study
title_sort	genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: a genome-wide association and polygenic scoring study
description	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. © 2014 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals, Inc.
publisher	BlackWell Publishing Ltd
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309466/
_version_	1613181657132564480

Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome-wide association and polygenic scoring study

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