TY - JOUR
T1 - Genomewide association scan of suicidal thoughts and behaviour in major depression
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.
UR - http://www.scopus.com/inward/record.url?scp=79959981469&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0020690
DO - 10.1371/journal.pone.0020690
M3 - Article
C2 - 21750702
AN - SCOPUS:79959981469
SN - 1932-6203
VL - 6
JO - PloS one
JF - PloS one
IS - 7
M1 - e20690
ER -