Article: Genomewide association scan of suicidal thoughts and behaviour in major depression

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TitleGenomewide association scan of suicidal thoughts and behaviour in major depression
AuthorsSchosser, 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 Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
CitationPLoS One, 2011, v. 6 n. 7, article no. e20690 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0020690
AbstractBACKGROUND: 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.
ISSN1932-6203
2011 Impact Factor: 4.092
2011 SCImago Journal Rankings: 0.519
DOIhttp://dx.doi.org/10.1371/journal.pone.0020690
PubMed Central IDPMC3130038
DC Field
Value
dc.contributor.authorSchosser, A
dc.contributor.authorButler, AW
dc.contributor.authorIsing, M
dc.contributor.authorPerroud, N
dc.contributor.authorUher, R
dc.contributor.authorNg, MY
dc.contributor.authorCohen-Woods, S
dc.contributor.authorCraddock, N
dc.contributor.authorOwen, MJ
dc.contributor.authorKorszun, A
dc.contributor.authorJones, L
dc.contributor.authorJones, I
dc.contributor.authorGill, M
dc.contributor.authorRice, JP
dc.contributor.authorMaier, W
dc.contributor.authorMors, O
dc.contributor.authorRietschel, M
dc.contributor.authorLucae, S
dc.contributor.authorBinder, EB
dc.contributor.authorPreisig, M
dc.contributor.authorPerry, J
dc.contributor.authorTozzi, F
dc.contributor.authorMuglia, P
dc.contributor.authorAitchison, KJ
dc.contributor.authorBreen, G
dc.contributor.authorCraig, IW
dc.contributor.authorFarmer, AE
dc.contributor.authorMulller-Myhsok, B
dc.contributor.authorMcGuffin, P
dc.contributor.authorLewis, CM
dc.date.accessioned2012-09-20T08:06:04Z
dc.date.available2012-09-20T08:06:04Z
dc.date.issued2011
dc.description.abstractBACKGROUND: 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.naturepublished_or_final_version
dc.identifier.citationPLoS One, 2011, v. 6 n. 7, article no. e20690 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0020690
dc.identifier.citeulike9595180
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0020690
dc.identifier.hkuros210464
dc.identifier.issn1932-6203
2011 Impact Factor: 4.092
2011 SCImago Journal Rankings: 0.519
dc.identifier.issue7, article no. e20690
dc.identifier.pmcidPMC3130038
dc.identifier.pmid21750702
dc.identifier.scopuseid_2-s2.0-79959981469
dc.identifier.urihttp://hdl.handle.net/10722/164567
dc.identifier.volume6
dc.languageeng
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
dc.publisher.placeUnited States
dc.relation.ispartofPLoS One
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
dc.subject.meshAlleles
dc.subject.meshDepressive Disorder, Major - genetics - psychology
dc.subject.meshGenome-Wide Association Study - methods
dc.subject.meshSuicidal Ideation
dc.subject.meshSuicide, Attempted
dc.titleGenomewide association scan of suicidal thoughts and behaviour in major depression
dc.typeArticle
Author Affiliations
  1. King's College London
  2. Universität Bonn
  3. Washington University in St. Louis
  4. South London and Maudsley NHS Foundation Trust
  5. The University of Hong Kong
  6. GlaxoSmithKline
  7. null
  8. Max-Planck-Institut für Psychiatrie
  9. Zentralinstitut für Seelische Gesundheit
  10. University of Birmingham
  11. Cardiff University
  12. Neurosearch AS
  13. Medizinische Universitat Wien
  14. Université de Genève
  15. University of Toronto
  16. Trinity Centre for Health Science
  17. Ârhus Universitetshospital
  18. Universität Lausanne Schweiz