Genome-wide association study of suicide attempts in mood disorder patients

Roy H. Perlis, Jie Huang, Shaun Purcell, Maurizio Fava, A. John Rush, Patrick F. Sullivan, Steven P. Hamilton, Francis J. McMahon, Thomas Schulze, James Bennett Potash, Peter P Zandi, Virginia L. Willour, Brenda W. Penninx, Dorret I. Boomsma, Nicole Vogelzangs, Christel M. Middeldorp, Marcella Rietschel, Markus Nöthen, Sven Cichon, Hugh GurlingNick Bass, Andrew McQuillin, Marian Hamshere, Nick Craddock, Pamela Sklar, Jordan W. Smoller

Research output: Contribution to journalArticle

Abstract

Objective: Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. Method: The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort. Results: Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. Conclusions: The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.

Original languageEnglish (US)
Pages (from-to)1499-1507
Number of pages9
JournalAmerican Journal of Psychiatry
Volume167
Issue number12
DOIs
StatePublished - Dec 2010
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Mood Disorders
Suicide
Bipolar Disorder
Depression
Netherlands
Anxiety
Protein Kinase C-epsilon
National Institute of Mental Health (U.S.)
Twin Studies
Information Services
Major Depressive Disorder
Single Nucleotide Polymorphism
Meta-Analysis
Therapeutics
Genes
Proteins

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Perlis, R. H., Huang, J., Purcell, S., Fava, M., Rush, A. J., Sullivan, P. F., ... Smoller, J. W. (2010). Genome-wide association study of suicide attempts in mood disorder patients. American Journal of Psychiatry, 167(12), 1499-1507. https://doi.org/10.1176/appi.ajp.2010.10040541

Genome-wide association study of suicide attempts in mood disorder patients. / Perlis, Roy H.; Huang, Jie; Purcell, Shaun; Fava, Maurizio; Rush, A. John; Sullivan, Patrick F.; Hamilton, Steven P.; McMahon, Francis J.; Schulze, Thomas; Potash, James Bennett; Zandi, Peter P; Willour, Virginia L.; Penninx, Brenda W.; Boomsma, Dorret I.; Vogelzangs, Nicole; Middeldorp, Christel M.; Rietschel, Marcella; Nöthen, Markus; Cichon, Sven; Gurling, Hugh; Bass, Nick; McQuillin, Andrew; Hamshere, Marian; Craddock, Nick; Sklar, Pamela; Smoller, Jordan W.

In: American Journal of Psychiatry, Vol. 167, No. 12, 12.2010, p. 1499-1507.

Research output: Contribution to journalArticle

Perlis, RH, Huang, J, Purcell, S, Fava, M, Rush, AJ, Sullivan, PF, Hamilton, SP, McMahon, FJ, Schulze, T, Potash, JB, Zandi, PP, Willour, VL, Penninx, BW, Boomsma, DI, Vogelzangs, N, Middeldorp, CM, Rietschel, M, Nöthen, M, Cichon, S, Gurling, H, Bass, N, McQuillin, A, Hamshere, M, Craddock, N, Sklar, P & Smoller, JW 2010, 'Genome-wide association study of suicide attempts in mood disorder patients', American Journal of Psychiatry, vol. 167, no. 12, pp. 1499-1507. https://doi.org/10.1176/appi.ajp.2010.10040541
Perlis, Roy H. ; Huang, Jie ; Purcell, Shaun ; Fava, Maurizio ; Rush, A. John ; Sullivan, Patrick F. ; Hamilton, Steven P. ; McMahon, Francis J. ; Schulze, Thomas ; Potash, James Bennett ; Zandi, Peter P ; Willour, Virginia L. ; Penninx, Brenda W. ; Boomsma, Dorret I. ; Vogelzangs, Nicole ; Middeldorp, Christel M. ; Rietschel, Marcella ; Nöthen, Markus ; Cichon, Sven ; Gurling, Hugh ; Bass, Nick ; McQuillin, Andrew ; Hamshere, Marian ; Craddock, Nick ; Sklar, Pamela ; Smoller, Jordan W. / Genome-wide association study of suicide attempts in mood disorder patients. In: American Journal of Psychiatry. 2010 ; Vol. 167, No. 12. pp. 1499-1507.
@article{ee65b939acf94ecb8cfa366852db3b26,
title = "Genome-wide association study of suicide attempts in mood disorder patients",
abstract = "Objective: Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. Method: The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort. Results: Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. Conclusions: The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.",
author = "Perlis, {Roy H.} and Jie Huang and Shaun Purcell and Maurizio Fava and Rush, {A. John} and Sullivan, {Patrick F.} and Hamilton, {Steven P.} and McMahon, {Francis J.} and Thomas Schulze and Potash, {James Bennett} and Zandi, {Peter P} and Willour, {Virginia L.} and Penninx, {Brenda W.} and Boomsma, {Dorret I.} and Nicole Vogelzangs and Middeldorp, {Christel M.} and Marcella Rietschel and Markus N{\"o}then and Sven Cichon and Hugh Gurling and Nick Bass and Andrew McQuillin and Marian Hamshere and Nick Craddock and Pamela Sklar and Smoller, {Jordan W.}",
year = "2010",
month = "12",
doi = "10.1176/appi.ajp.2010.10040541",
language = "English (US)",
volume = "167",
pages = "1499--1507",
journal = "American Journal of Psychiatry",
issn = "0002-953X",
publisher = "American Psychiatric Association",
number = "12",

}

TY - JOUR

T1 - Genome-wide association study of suicide attempts in mood disorder patients

AU - Perlis, Roy H.

AU - Huang, Jie

AU - Purcell, Shaun

AU - Fava, Maurizio

AU - Rush, A. John

AU - Sullivan, Patrick F.

AU - Hamilton, Steven P.

AU - McMahon, Francis J.

AU - Schulze, Thomas

AU - Potash, James Bennett

AU - Zandi, Peter P

AU - Willour, Virginia L.

AU - Penninx, Brenda W.

AU - Boomsma, Dorret I.

AU - Vogelzangs, Nicole

AU - Middeldorp, Christel M.

AU - Rietschel, Marcella

AU - Nöthen, Markus

AU - Cichon, Sven

AU - Gurling, Hugh

AU - Bass, Nick

AU - McQuillin, Andrew

AU - Hamshere, Marian

AU - Craddock, Nick

AU - Sklar, Pamela

AU - Smoller, Jordan W.

PY - 2010/12

Y1 - 2010/12

N2 - Objective: Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. Method: The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort. Results: Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. Conclusions: The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.

AB - Objective: Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. Method: The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort. Results: Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. Conclusions: The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.

UR - http://www.scopus.com/inward/record.url?scp=78649743723&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649743723&partnerID=8YFLogxK

U2 - 10.1176/appi.ajp.2010.10040541

DO - 10.1176/appi.ajp.2010.10040541

M3 - Article

C2 - 21041247

AN - SCOPUS:78649743723

VL - 167

SP - 1499

EP - 1507

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

SN - 0002-953X

IS - 12

ER -