title: Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms.
abstract: BACKGROUND
  Suicidal behaviour is known to aggregate in families. Patients with psychiatric disorders are at higher risk for suicide attempts (SA), however protective and risk genetic variants for suicide appear to be independent of underlying psychiatric disorders. Here we investigate genetic variants in genes important for neurobiological pathways linked to suicidal behaviour and/or associated endophenotypes, for association with SA among patients with co-existing psychiatric illness. Selected gene-gene and gene-environment interactions were also tested.
  
  
  METHODS
  DNA was obtained from bloods of 159 patients (76 suicide attempters and 83 non-attempters), who were profiled for DSM-IV Axis I psychiatric diagnosis. Twenty-eight single nucleotide polymorphisms (SNPs) from 18 candidate genes (COMT, 5-HT2A, 5-HT1A, 5-HTR1B, TPH1, MAO-A, TPH2, DBH, CNR1, BDNF, ABCG1, GABRA5, GABRG2, GABRB2, SLC1A2, SLC1A3, NTRK2, CRHR1) were genotyped. Genotyping was performed by KBioscience. Tests of association between genetic variants and SA were conducted using Chi squared and Armitage Trend tests. Binary logistical regression analyses were performed to evaluate the contribution of individual genetic variants to the prediction of SA, and to examine SNPs for potential gene-gene and gene-environment interactions.
  
  
  RESULTS
  Our analysis identified 4 SNPs (rs4755404, rs2269272, rs6296 and rs1659400), which showed evidence of association with SA compared to a non-attempter control group. We provide evidence of a 3-locus gene-gene interaction, and a putative gene-environment interaction, whereby genetic variation at the NTRK2 locus may moderate the risk associated with history of childhood abuse.
  
  
  CONCLUSIONS
  Preliminary findings suggest that allelic variability in SLC1A2/3, 5-HTR1B and NTRK2 may be relevant to the underlying diathesis for suicidal acts.
authors.affiliation: Department of Psychiatry & Mental Health Research, St. Vincent's University Hospital, University College Dublin, Elm Park, Dublin 4, Ireland. murphyth@tcd.ie
authors.forename: Therese M
authors.initials: TM
authors.lastname: Murphy
authors.forename: Maria
authors.initials: M
authors.lastname: Ryan
authors.forename: Tom
authors.initials: T
authors.lastname: Foster
authors.forename: Chris
authors.initials: C
authors.lastname: Kelly
authors.forename: Roy
authors.initials: R
authors.lastname: McClelland
authors.forename: John
authors.initials: J
authors.lastname: O'Grady
authors.forename: Eleanor
authors.initials: E
authors.lastname: Corcoran
authors.forename: John
authors.initials: J
authors.lastname: Brady
authors.forename: Michael
authors.initials: M
authors.lastname: Reilly
authors.forename: Anne
authors.initials: A
authors.lastname: Jeffers
authors.forename: Katherine
authors.initials: K
authors.lastname: Brown
authors.forename: Anne
authors.initials: A
authors.lastname: Maher
authors.forename: Noreen
authors.initials: N
authors.lastname: Bannan
authors.forename: Alison
authors.initials: A
authors.lastname: Casement
authors.forename: Dermot
authors.initials: D
authors.lastname: Lynch
authors.forename: Sharon
authors.initials: S
authors.lastname: Bolger
authors.forename: Prerna
authors.initials: P
authors.lastname: Tewari
authors.forename: Avril
authors.initials: A
authors.lastname: Buckley
authors.forename: Leah
authors.initials: L
authors.lastname: Quinlivan
authors.forename: Leslie
authors.initials: L
authors.lastname: Daly
authors.forename: Cecily
authors.initials: C
authors.lastname: Kelleher
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Malone
mesh_terms: D000328:Adult; D058068:Endophenotypes; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics*; D027342:Excitatory Amino Acid Transporter 2; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D050491:Glutamate Plasma Membrane Transport Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000235:genetics* / Q000523:psychology; D018377:Neurotransmitter Agents / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics*; D020813:Receptor, trkB / Q000235:genetics*; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics; D013406:Suicide, Attempted / Q000523:psychology*
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; D018377:Neurotransmitter Agents; D044302:Receptor, Serotonin, 5-HT1B; C493397:SLC1A2 protein, human; C493394:SLC1A3 protein, human; D020813:Receptor, trkB