Behavioral and Brain Functions (Jun 2011)

Risk and protective genetic variants in suicidal behaviour: association with <it>SLC1A2, SLC1A3, 5-HTR1B </it>&<it>NTRK2 </it>polymorphisms

  • Buckley Avril,
  • Tewari Prerna,
  • Bolger Sharon,
  • Lynch Dermot,
  • Casement Alison,
  • Bannan Noreen,
  • Maher Anne,
  • Brown Katherine,
  • Jeffers Anne,
  • Reilly Michael,
  • Brady John,
  • O'Grady John,
  • Corcoran Eleanor,
  • McClelland Roy,
  • Foster Tom,
  • Kelly Chris,
  • Ryan Maria,
  • Murphy Therese M,
  • Quinlivan Leah,
  • Daly Leslie,
  • Kelleher Cecily,
  • Malone Kevin M

DOI
https://doi.org/10.1186/1744-9081-7-22
Journal volume & issue
Vol. 7, no. 1
p. 22

Abstract

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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. Conclusion Preliminary findings suggest that allelic variability in SLC1A2/3, 5-HTR1B and NTRK2 may be relevant to the underlying diathesis for suicidal acts.