Article: Genomewide association scan of suicidal thoughts and behaviour in major depression
| Title | Genomewide association scan of suicidal thoughts and behaviour in major depression |
|---|---|
| Authors | Schosser, A1 13 Butler, AW1 5 Ising, M8 Perroud, N1 14 Uher, R1 Ng, MY1 Cohen-Woods, S1 Craddock, N11 Owen, MJ11 Korszun, A7 Jones, L10 Jones, I11 Gill, M16 Rice, JP3 Maier, W2 Mors, O17 Rietschel, M9 Lucae, S8 Binder, EB8 Preisig, M18 Perry, J6 Tozzi, F6 Muglia, P6 12 15 Aitchison, KJ1 Breen, G1 4 Craig, IW1 Farmer, AE1 Mulller-Myhsok, B McGuffin, P1 Lewis, CM1 |
| Issue Date | 2011 |
| Publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action |
| Citation | PLoS One, 2011, v. 6 n. 7, article no. e20690 [How to Cite?] DOI: http://dx.doi.org/10.1371/journal.pone.0020690 |
| 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. |
| ISSN | 1932-6203 2011 Impact Factor: 4.092 2011 SCImago Journal Rankings: 0.519 |
| DOI | http://dx.doi.org/10.1371/journal.pone.0020690 |
| PubMed Central ID | PMC3130038 |
| dc.contributor.author | Schosser, A |
|---|---|
| dc.contributor.author | Butler, AW |
| dc.contributor.author | Ising, M |
| dc.contributor.author | Perroud, N |
| dc.contributor.author | Uher, R |
| dc.contributor.author | Ng, MY |
| dc.contributor.author | Cohen-Woods, S |
| dc.contributor.author | Craddock, N |
| dc.contributor.author | Owen, MJ |
| dc.contributor.author | Korszun, A |
| dc.contributor.author | Jones, L |
| dc.contributor.author | Jones, I |
| dc.contributor.author | Gill, M |
| dc.contributor.author | Rice, JP |
| dc.contributor.author | Maier, W |
| dc.contributor.author | Mors, O |
| dc.contributor.author | Rietschel, M |
| dc.contributor.author | Lucae, S |
| dc.contributor.author | Binder, EB |
| dc.contributor.author | Preisig, M |
| dc.contributor.author | Perry, J |
| dc.contributor.author | Tozzi, F |
| dc.contributor.author | Muglia, P |
| dc.contributor.author | Aitchison, KJ |
| dc.contributor.author | Breen, G |
| dc.contributor.author | Craig, IW |
| dc.contributor.author | Farmer, AE |
| dc.contributor.author | Mulller-Myhsok, B |
| dc.contributor.author | McGuffin, P |
| dc.contributor.author | Lewis, CM |
| dc.date.accessioned | 2012-09-20T08:06:04Z |
| dc.date.available | 2012-09-20T08:06:04Z |
| dc.date.issued | 2011 |
| dc.description.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. |
| dc.description.nature | published_or_final_version |
| dc.identifier.citation | PLoS One, 2011, v. 6 n. 7, article no. e20690 [How to Cite?] DOI: http://dx.doi.org/10.1371/journal.pone.0020690 |
| dc.identifier.citeulike | 9595180 |
| dc.identifier.doi | http://dx.doi.org/10.1371/journal.pone.0020690 |
| dc.identifier.hkuros | 210464 |
| dc.identifier.issn | 1932-6203 2011 Impact Factor: 4.092 2011 SCImago Journal Rankings: 0.519 |
| dc.identifier.issue | 7, article no. e20690 |
| dc.identifier.pmcid | PMC3130038 |
| dc.identifier.pmid | 21750702 |
| dc.identifier.scopus | eid_2-s2.0-79959981469 |
| dc.identifier.uri | http://hdl.handle.net/10722/164567 |
| dc.identifier.volume | 6 |
| dc.language | eng |
| dc.publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action |
| dc.publisher.place | United States |
| dc.relation.ispartof | PLoS One |
| dc.rights | Creative Commons: Attribution 3.0 Hong Kong License |
| dc.subject.mesh | Alleles |
| dc.subject.mesh | Depressive Disorder, Major - genetics - psychology |
| dc.subject.mesh | Genome-Wide Association Study - methods |
| dc.subject.mesh | Suicidal Ideation |
| dc.subject.mesh | Suicide, Attempted |
| dc.title | Genomewide association scan of suicidal thoughts and behaviour in major depression |
| dc.type | Article |
Author Affiliations
- King's College London
- Universität Bonn
- Washington University in St. Louis
- South London and Maudsley NHS Foundation Trust
- The University of Hong Kong
- GlaxoSmithKline
- null
- Max-Planck-Institut für Psychiatrie
- Zentralinstitut für Seelische Gesundheit
- University of Birmingham
- Cardiff University
- Neurosearch AS
- Medizinische Universitat Wien
- Université de Genève
- University of Toronto
- Trinity Centre for Health Science
- Ârhus Universitetshospital
- Universität Lausanne Schweiz

