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.
  
  
  RESULTS
  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
  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.
authors.affiliation: MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schosser
authors.forename: Amy W
authors.initials: AW
authors.lastname: Butler
authors.forename: Marcus
authors.initials: M
authors.lastname: Ising
authors.forename: Nader
authors.initials: N
authors.lastname: Perroud
authors.forename: Rudolf
authors.initials: R
authors.lastname: Uher
authors.forename: Mandy Y
authors.initials: MY
authors.lastname: Ng
authors.forename: Sarah
authors.initials: S
authors.lastname: Cohen-Woods
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Ania
authors.initials: A
authors.lastname: Korszun
authors.forename: Lisa
authors.initials: L
authors.lastname: Jones
authors.forename: Ian
authors.initials: I
authors.lastname: Jones
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Susanne
authors.initials: S
authors.lastname: Lucae
authors.forename: Elisabeth B
authors.initials: EB
authors.lastname: Binder
authors.forename: Martin
authors.initials: M
authors.lastname: Preisig
authors.forename: Julia
authors.initials: J
authors.lastname: Perry
authors.forename: Federica
authors.initials: F
authors.lastname: Tozzi
authors.forename: Pierandrea
authors.initials: P
authors.lastname: Muglia
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Aitchison
authors.forename: Gerome
authors.initials: G
authors.lastname: Breen
authors.forename: Ian W
authors.initials: IW
authors.lastname: Craig
authors.forename: Anne E
authors.initials: AE
authors.lastname: Farmer
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Lewis
mesh_terms: D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000235:genetics* / Q000523:psychology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D059020:Suicidal Ideation; D013406:Suicide, Attempted