Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms.
Authors
Murphy, Therese MRyan, Maria
Foster, Tom
Kelly, Chris
McClelland, Roy
O'Grady, John
Corcoran, Eleanor
Brady, John
Reilly, Michael
Jeffers, Anne
Brown, Katherine
Maher, Anne
Bannan, Noreen
Casement, Alison
Lynch, Dermot
Bolger, Sharon
Tewari, Prerna
Buckley, Avril
Quinlivan, Leah
Daly, Leslie
Kelleher, Cecily
Malone, Kevin M
Affiliation
Department of Psychiatry & Mental Health Research, St. Vincent's University, Hospital, University College Dublin, Elm Park, Dublin 4, Ireland. murphyth@tcd.ieIssue Date
2012-02-01T10:28:30ZMeSH
AdultEndophenotypes
Excitatory Amino Acid Transporter 1/*genetics
Female
Genetic Association Studies/*methods
Genetic Predisposition to Disease/genetics
Genotype
Glutamate Plasma Membrane Transport Proteins/*genetics
Humans
Male
Mental Disorders/complications/*genetics/psychology
Neurotransmitter Agents/genetics
Polymorphism, Single Nucleotide
Receptor, Serotonin, 5-HT1B/*genetics
Receptor, trkB/*genetics
Risk Factors
Signal Transduction/genetics
Suicide, Attempted/*psychology
Metadata
Show full item recordCitation
Behav Brain Funct. 2011 Jun 28;7:22.Journal
Behavioral and brain functions : BBFDOI
10.1186/1744-9081-7-22PubMed ID
21711518Abstract
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.Language
engISSN
1744-9081 (Electronic)1744-9081 (Linking)
ae974a485f413a2113503eed53cd6c53
10.1186/1744-9081-7-22
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