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

Hdl Handle:
http://hdl.handle.net/10147/207023
Title:
Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms.
Authors:
Murphy, Therese M; Ryan, 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.ie
Citation:
Behav Brain Funct. 2011 Jun 28;7:22.
Journal:
Behavioral and brain functions : BBF
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207023
DOI:
10.1186/1744-9081-7-22
PubMed ID:
21711518
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.
Language:
eng
MeSH:
Adult; Endophenotypes; 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
ISSN:
1744-9081 (Electronic); 1744-9081 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorMurphy, Therese Men_GB
dc.contributor.authorRyan, Mariaen_GB
dc.contributor.authorFoster, Tomen_GB
dc.contributor.authorKelly, Chrisen_GB
dc.contributor.authorMcClelland, Royen_GB
dc.contributor.authorO'Grady, Johnen_GB
dc.contributor.authorCorcoran, Eleanoren_GB
dc.contributor.authorBrady, Johnen_GB
dc.contributor.authorReilly, Michaelen_GB
dc.contributor.authorJeffers, Anneen_GB
dc.contributor.authorBrown, Katherineen_GB
dc.contributor.authorMaher, Anneen_GB
dc.contributor.authorBannan, Noreenen_GB
dc.contributor.authorCasement, Alisonen_GB
dc.contributor.authorLynch, Dermoten_GB
dc.contributor.authorBolger, Sharonen_GB
dc.contributor.authorTewari, Prernaen_GB
dc.contributor.authorBuckley, Avrilen_GB
dc.contributor.authorQuinlivan, Leahen_GB
dc.contributor.authorDaly, Leslieen_GB
dc.contributor.authorKelleher, Cecilyen_GB
dc.contributor.authorMalone, Kevin Men_GB
dc.date.accessioned2012-02-01T10:28:30Z-
dc.date.available2012-02-01T10:28:30Z-
dc.date.issued2012-02-01T10:28:30Z-
dc.identifier.citationBehav Brain Funct. 2011 Jun 28;7:22.en_GB
dc.identifier.issn1744-9081 (Electronic)en_GB
dc.identifier.issn1744-9081 (Linking)en_GB
dc.identifier.pmid21711518en_GB
dc.identifier.doi10.1186/1744-9081-7-22en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207023-
dc.description.abstractBACKGROUND: 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAdulten_GB
dc.subject.meshEndophenotypesen_GB
dc.subject.meshExcitatory Amino Acid Transporter 1/*geneticsen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGenetic Association Studies/*methodsen_GB
dc.subject.meshGenetic Predisposition to Disease/geneticsen_GB
dc.subject.meshGenotypeen_GB
dc.subject.meshGlutamate Plasma Membrane Transport Proteins/*geneticsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMental Disorders/complications/*genetics/psychologyen_GB
dc.subject.meshNeurotransmitter Agents/geneticsen_GB
dc.subject.meshPolymorphism, Single Nucleotideen_GB
dc.subject.meshReceptor, Serotonin, 5-HT1B/*geneticsen_GB
dc.subject.meshReceptor, trkB/*geneticsen_GB
dc.subject.meshRisk Factorsen_GB
dc.subject.meshSignal Transduction/geneticsen_GB
dc.subject.meshSuicide, Attempted/*psychologyen_GB
dc.titleRisk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms.en_GB
dc.contributor.departmentDepartment of Psychiatry & Mental Health Research, St. Vincent's University, Hospital, University College Dublin, Elm Park, Dublin 4, Ireland. murphyth@tcd.ieen_GB
dc.identifier.journalBehavioral and brain functions : BBFen_GB
dc.description.provinceLeinster-

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