Genomewide association scan of suicidal thoughts and behaviour in major depression

Alexandra Schosser; Amy W. Butler; Marcus Ising; Nader Perroud; Rudolf Uher; Mandy Y. Ng; Sarah Cohen-Woods; Nick Craddock; Michael J. Owen; Ania Korszun; Lisa Jones; Ian Jones; Michael Gill; John P. Rice; Wolfgang Maier; Ole Mors; Marcella Rietschel; Susanne Lucae; Elisabeth B. Binder; Martin Preisig; Julia Perry; Federica Tozzi; Pierandrea Muglia; Katherine J. Aitchison; Gerome Breen; Ian W. Craig; Anne E. Farmer; Bertram Müller-Myhsok; Peter McGuffin; Cathryn M. Lewis

doi:10.1371/journal.pone.0020690

Genomewide association scan of suicidal thoughts and behaviour in major depression

Alexandra Schosser, Amy W. Butler, Marcus Ising, Nader Perroud, Rudolf Uher, Mandy Y. Ng, Sarah Cohen-Woods, Nick Craddock, Michael J. Owen, Ania Korszun, Lisa Jones, Ian Jones, Michael Gill, John P. Rice, Wolfgang Maier, Ole Mors, Marcella Rietschel, Susanne Lucae, Elisabeth B. Binder, Martin PreisigJulia Perry, Federica Tozzi, Pierandrea Muglia, Katherine J. Aitchison, Gerome Breen, Ian W. Craig, Anne E. Farmer, Bertram Müller-Myhsok, Peter McGuffin, Cathryn M. Lewis

Research output: Contribution to journal › Article › peer-review

93 Citations (Scopus)

Abstract

Background: Suicidal behaviour can be conceptualised as a continuum from suicidal ideation, to suicidal attempts to completed suicide. In this study we identify genes contributing to suicidal behaviour in the depression study RADIANT. Methodology/Principal Findings: A quantitative suicidality score was composed of two items from the SCAN interview. In addition, the 251 depression cases with a history of serious suicide attempts were classified to form a discrete trait. The quantitative trait was correlated with younger onset of depression and number of episodes of depression, but not with gender. A genome-wide association study of 2,023 depression cases was performed to identify genes that may contribute to suicidal behaviour. Two Munich depression studies were used as replication cohorts to test the most strongly associated SNPs. No SNP was associated at genome-wide significance level. For the quantitative trait, evidence of association was detected at GFRA1, a receptor for the neurotrophin GDRA (p = 2e-06). For the discrete trait of suicide attempt, SNPs in KIAA1244 and RGS18 attained p-values of <5e-6. None of these SNPs showed evidence for replication in the additional cohorts tested. Candidate gene analysis provided some support for a polymorphism in NTRK2, which was previously associated with suicidality. Conclusions/Significance: This study provides a genome-wide assessment of possible genetic contribution to suicidal behaviour in depression but indicates a genetic architecture of multiple genes with small effects. Large cohorts will be required to dissect this further.

Original language	English
Article number	e20690
Journal	PLoS One
Volume	6
Issue number	7
DOIs	https://doi.org/10.1371/journal.pone.0020690
Publication status	Published - 2011
Externally published	Yes

Bibliographical note

Funding Information:
Aitchison, Farmer and McGuffin have received consultancy fees and honoraria for participating in expert panels for pharmaceutical companies, including GlaxoSmithKline. Aitchison declares interests through Advisory Boards for Johnson & Johnson, Lundbeck, Roche Diagnostics, and Bristol-Myers Squibb; membership of Bristol-Myers Squibb UK Steering group 2003 to present; consultancy work for Roche Diagnostics, Johnson & Johnson Pharmaceutical Research and Development, Lundbeck, and Bristol-Myers Squibb Pharmaceuticals Limited; grants awarded by Johnson & Johnson Pharmaceutical Research & Development, Bristol-Myers Squibb Pharmaceuticals Limited, and E Merck Pharmaceuticals. Souery is involved in advisory boards for Astra Zeneca, Eli Lilly, BMS, Janssen-Cilag and Lundbeck. Perry is an employee of GlaxoSmithKline; Muglia and Tozzi were employees of GlaxoSmithKline when the research was performed. Henigsberg has participated in clinical trials sponsored by pharmaceutical companies including GlaxoSmithKline, and Lundbeck and has received honoraria for participating in expert panels for pharmaceutical companies including Lundbeck. Ising has received consultancy honoraria from MSD Merck. Binder has received grant support from PharmaNeuroboost. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials, as detailed online in the guide for authors. All other authors (Schosser, Butler, Perroud, Uher, Ng, Cohen-Woods, Craddock, Owen Korszun, Jones I, Jones L, Gill, Rice, Hauser, Maier, Zobel, Mors, Placentino, Rietschel, Souery, Kozel, Lucae, Preisig, Breen, Craig, Müller-Myhsok, and Lewis) declare no conflicts of interest.

ASJC Scopus Subject Areas

General

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0020690

Cite this

Schosser, A., Butler, A. W., Ising, M., Perroud, N., Uher, R., Ng, M. Y., Cohen-Woods, S., Craddock, N., Owen, M. J., Korszun, A., Jones, L., Jones, I., Gill, M., Rice, J. P., Maier, W., Mors, O., Rietschel, M., Lucae, S., Binder, E. B., ... Lewis, C. M. (2011). Genomewide association scan of suicidal thoughts and behaviour in major depression. PLoS One, 6(7), Article e20690. https://doi.org/10.1371/journal.pone.0020690

Schosser, A, Butler, AW, Ising, M, Perroud, N, Uher, R, Ng, MY, Cohen-Woods, S, Craddock, N, Owen, MJ, Korszun, A, Jones, L, Jones, I, Gill, M, Rice, JP, Maier, W, Mors, O, Rietschel, M, Lucae, S, Binder, EB, Preisig, M, Perry, J, Tozzi, F, Muglia, P, Aitchison, KJ, Breen, G, Craig, IW, Farmer, AE, Müller-Myhsok, B, McGuffin, P & Lewis, CM 2011, 'Genomewide association scan of suicidal thoughts and behaviour in major depression', PLoS One, vol. 6, no. 7, e20690. https://doi.org/10.1371/journal.pone.0020690

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title = "Genomewide association scan of suicidal thoughts and behaviour in major depression",

abstract = "Background: Suicidal behaviour can be conceptualised as a continuum from suicidal ideation, to suicidal attempts to completed suicide. In this study we identify genes contributing to suicidal behaviour in the depression study RADIANT. Methodology/Principal Findings: A quantitative suicidality score was composed of two items from the SCAN interview. In addition, the 251 depression cases with a history of serious suicide attempts were classified to form a discrete trait. The quantitative trait was correlated with younger onset of depression and number of episodes of depression, but not with gender. A genome-wide association study of 2,023 depression cases was performed to identify genes that may contribute to suicidal behaviour. Two Munich depression studies were used as replication cohorts to test the most strongly associated SNPs. No SNP was associated at genome-wide significance level. For the quantitative trait, evidence of association was detected at GFRA1, a receptor for the neurotrophin GDRA (p = 2e-06). For the discrete trait of suicide attempt, SNPs in KIAA1244 and RGS18 attained p-values of <5e-6. None of these SNPs showed evidence for replication in the additional cohorts tested. Candidate gene analysis provided some support for a polymorphism in NTRK2, which was previously associated with suicidality. Conclusions/Significance: This study provides a genome-wide assessment of possible genetic contribution to suicidal behaviour in depression but indicates a genetic architecture of multiple genes with small effects. Large cohorts will be required to dissect this further.",

author = "Alexandra Schosser and Butler, {Amy W.} and Marcus Ising and Nader Perroud and Rudolf Uher and Ng, {Mandy Y.} and Sarah Cohen-Woods and Nick Craddock and Owen, {Michael J.} and Ania Korszun and Lisa Jones and Ian Jones and Michael Gill and Rice, {John P.} and Wolfgang Maier and Ole Mors and Marcella Rietschel and Susanne Lucae and Binder, {Elisabeth B.} and Martin Preisig and Julia Perry and Federica Tozzi and Pierandrea Muglia and Aitchison, {Katherine J.} and Gerome Breen and Craig, {Ian W.} and Farmer, {Anne E.} and Bertram M{\"u}ller-Myhsok and Peter McGuffin and Lewis, {Cathryn M.}",

note = "Funding Information: Aitchison, Farmer and McGuffin have received consultancy fees and honoraria for participating in expert panels for pharmaceutical companies, including GlaxoSmithKline. Aitchison declares interests through Advisory Boards for Johnson & Johnson, Lundbeck, Roche Diagnostics, and Bristol-Myers Squibb; membership of Bristol-Myers Squibb UK Steering group 2003 to present; consultancy work for Roche Diagnostics, Johnson & Johnson Pharmaceutical Research and Development, Lundbeck, and Bristol-Myers Squibb Pharmaceuticals Limited; grants awarded by Johnson & Johnson Pharmaceutical Research & Development, Bristol-Myers Squibb Pharmaceuticals Limited, and E Merck Pharmaceuticals. Souery is involved in advisory boards for Astra Zeneca, Eli Lilly, BMS, Janssen-Cilag and Lundbeck. Perry is an employee of GlaxoSmithKline; Muglia and Tozzi were employees of GlaxoSmithKline when the research was performed. Henigsberg has participated in clinical trials sponsored by pharmaceutical companies including GlaxoSmithKline, and Lundbeck and has received honoraria for participating in expert panels for pharmaceutical companies including Lundbeck. Ising has received consultancy honoraria from MSD Merck. Binder has received grant support from PharmaNeuroboost. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials, as detailed online in the guide for authors. All other authors (Schosser, Butler, Perroud, Uher, Ng, Cohen-Woods, Craddock, Owen Korszun, Jones I, Jones L, Gill, Rice, Hauser, Maier, Zobel, Mors, Placentino, Rietschel, Souery, Kozel, Lucae, Preisig, Breen, Craig, M{\"u}ller-Myhsok, and Lewis) declare no conflicts of interest. ",

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doi = "10.1371/journal.pone.0020690",

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AU - Schosser, Alexandra

AU - Butler, Amy W.

AU - Ising, Marcus

AU - Perroud, Nader

AU - Uher, Rudolf

AU - Ng, Mandy Y.

AU - Cohen-Woods, Sarah

AU - Craddock, Nick

AU - Owen, Michael J.

AU - Korszun, Ania

AU - Jones, Lisa

AU - Jones, Ian

AU - Gill, Michael

AU - Rice, John P.

AU - Maier, Wolfgang

AU - Mors, Ole

AU - Rietschel, Marcella

AU - Lucae, Susanne

AU - Binder, Elisabeth B.

AU - Preisig, Martin

AU - Perry, Julia

AU - Tozzi, Federica

AU - Muglia, Pierandrea

AU - Aitchison, Katherine J.

AU - Breen, Gerome

AU - Craig, Ian W.

AU - Farmer, Anne E.

AU - Müller-Myhsok, Bertram

AU - McGuffin, Peter

AU - Lewis, Cathryn M.

N1 - Funding Information: Aitchison, Farmer and McGuffin have received consultancy fees and honoraria for participating in expert panels for pharmaceutical companies, including GlaxoSmithKline. Aitchison declares interests through Advisory Boards for Johnson & Johnson, Lundbeck, Roche Diagnostics, and Bristol-Myers Squibb; membership of Bristol-Myers Squibb UK Steering group 2003 to present; consultancy work for Roche Diagnostics, Johnson & Johnson Pharmaceutical Research and Development, Lundbeck, and Bristol-Myers Squibb Pharmaceuticals Limited; grants awarded by Johnson & Johnson Pharmaceutical Research & Development, Bristol-Myers Squibb Pharmaceuticals Limited, and E Merck Pharmaceuticals. Souery is involved in advisory boards for Astra Zeneca, Eli Lilly, BMS, Janssen-Cilag and Lundbeck. Perry is an employee of GlaxoSmithKline; Muglia and Tozzi were employees of GlaxoSmithKline when the research was performed. Henigsberg has participated in clinical trials sponsored by pharmaceutical companies including GlaxoSmithKline, and Lundbeck and has received honoraria for participating in expert panels for pharmaceutical companies including Lundbeck. Ising has received consultancy honoraria from MSD Merck. Binder has received grant support from PharmaNeuroboost. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials, as detailed online in the guide for authors. All other authors (Schosser, Butler, Perroud, Uher, Ng, Cohen-Woods, Craddock, Owen Korszun, Jones I, Jones L, Gill, Rice, Hauser, Maier, Zobel, Mors, Placentino, Rietschel, Souery, Kozel, Lucae, Preisig, Breen, Craig, Müller-Myhsok, and Lewis) declare no conflicts of interest.

PY - 2011

Y1 - 2011

N2 - Background: Suicidal behaviour can be conceptualised as a continuum from suicidal ideation, to suicidal attempts to completed suicide. In this study we identify genes contributing to suicidal behaviour in the depression study RADIANT. Methodology/Principal Findings: A quantitative suicidality score was composed of two items from the SCAN interview. In addition, the 251 depression cases with a history of serious suicide attempts were classified to form a discrete trait. The quantitative trait was correlated with younger onset of depression and number of episodes of depression, but not with gender. A genome-wide association study of 2,023 depression cases was performed to identify genes that may contribute to suicidal behaviour. Two Munich depression studies were used as replication cohorts to test the most strongly associated SNPs. No SNP was associated at genome-wide significance level. For the quantitative trait, evidence of association was detected at GFRA1, a receptor for the neurotrophin GDRA (p = 2e-06). For the discrete trait of suicide attempt, SNPs in KIAA1244 and RGS18 attained p-values of <5e-6. None of these SNPs showed evidence for replication in the additional cohorts tested. Candidate gene analysis provided some support for a polymorphism in NTRK2, which was previously associated with suicidality. Conclusions/Significance: This study provides a genome-wide assessment of possible genetic contribution to suicidal behaviour in depression but indicates a genetic architecture of multiple genes with small effects. Large cohorts will be required to dissect this further.

AB - Background: Suicidal behaviour can be conceptualised as a continuum from suicidal ideation, to suicidal attempts to completed suicide. In this study we identify genes contributing to suicidal behaviour in the depression study RADIANT. Methodology/Principal Findings: A quantitative suicidality score was composed of two items from the SCAN interview. In addition, the 251 depression cases with a history of serious suicide attempts were classified to form a discrete trait. The quantitative trait was correlated with younger onset of depression and number of episodes of depression, but not with gender. A genome-wide association study of 2,023 depression cases was performed to identify genes that may contribute to suicidal behaviour. Two Munich depression studies were used as replication cohorts to test the most strongly associated SNPs. No SNP was associated at genome-wide significance level. For the quantitative trait, evidence of association was detected at GFRA1, a receptor for the neurotrophin GDRA (p = 2e-06). For the discrete trait of suicide attempt, SNPs in KIAA1244 and RGS18 attained p-values of <5e-6. None of these SNPs showed evidence for replication in the additional cohorts tested. Candidate gene analysis provided some support for a polymorphism in NTRK2, which was previously associated with suicidality. Conclusions/Significance: This study provides a genome-wide assessment of possible genetic contribution to suicidal behaviour in depression but indicates a genetic architecture of multiple genes with small effects. Large cohorts will be required to dissect this further.

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Genomewide association scan of suicidal thoughts and behaviour in major depression

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

UN SDGs

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