TY - JOUR
T1 - Risk and protective genetic variants in suicidal behaviour
T2 - Association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms
AU - Murphy, Therese M.
AU - Ryan, Maria
AU - Foster, Tom
AU - Kelly, Chris
AU - McClelland, Roy
AU - O'Grady, John
AU - Corcoran, Eleanor
AU - Brady, John
AU - Reilly, Michael
AU - Jeffers, Anne
AU - Brown, Katherine
AU - Maher, Anne
AU - Bannan, Noreen
AU - Casement, Alison
AU - Lynch, Dermot
AU - Bolger, Sharon
AU - Tewari, Prerna
AU - Buckley, Avril
AU - Quinlivan, Leah
AU - Daly, Leslie
AU - Kelleher, Cecily
AU - Malone, Kevin M.
N1 - Funding Information:
We acknowledge funding from the Craig-Dobbin Newman Fellowship in Mental Health Research and the Programme for Research in Third-Level Institutions (PRTCI) and statistical advice from the Centre for Support and Training in Analysis and Research (CSTAR), University College Dublin. We would like to acknowledge assistance from Aggie Boylan, Hammad Khan and Sharyn Carley.
PY - 2011/6/28
Y1 - 2011/6/28
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/79959617669
U2 - 10.1186/1744-9081-7-22
DO - 10.1186/1744-9081-7-22
M3 - Article
C2 - 21711518
AN - SCOPUS:79959617669
SN - 1744-9081
VL - 7
JO - Behavioral and Brain Functions
JF - Behavioral and Brain Functions
M1 - 22
ER -
