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

Hdl Handle:
http://hdl.handle.net/10147/582343
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
Citation:
Behavioral and Brain Functions. 2011 Jun 28;7(1):22
Issue Date:
28-Jun-2011
URI:
http://dx.doi.org/10.1186/1744-9081-7-22; http://hdl.handle.net/10147/582343
Abstract:
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:
en
Keywords:
SUICIDE; GENETICS

Full metadata record

DC FieldValue Language
dc.contributor.authorMurphy, Therese Men
dc.contributor.authorRyan, Mariaen
dc.contributor.authorFoster, Tomen
dc.contributor.authorKelly, Chrisen
dc.contributor.authorMcClelland, Royen
dc.contributor.authorO'Grady, Johnen
dc.contributor.authorCorcoran, Eleanoren
dc.contributor.authorBrady, Johnen
dc.contributor.authorReilly, Michaelen
dc.contributor.authorJeffers, Anneen
dc.contributor.authorBrown, Katherineen
dc.contributor.authorMaher, Anneen
dc.contributor.authorBannan, Noreenen
dc.contributor.authorCasement, Alisonen
dc.contributor.authorLynch, Dermoten
dc.contributor.authorBolger, Sharonen
dc.contributor.authorTewari, Prernaen
dc.contributor.authorBuckley, Avrilen
dc.contributor.authorQuinlivan, Leahen
dc.contributor.authorDaly, Leslieen
dc.contributor.authorKelleher, Cecilyen
dc.contributor.authorMalone, Kevin Men
dc.date.accessioned2015-11-18T16:21:29Zen
dc.date.available2015-11-18T16:21:29Zen
dc.date.issued2011-06-28en
dc.identifier.citationBehavioral and Brain Functions. 2011 Jun 28;7(1):22en
dc.identifier.urihttp://dx.doi.org/10.1186/1744-9081-7-22en
dc.identifier.urihttp://hdl.handle.net/10147/582343en
dc.description.abstractAbstract 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.en
dc.language.isoenen
dc.subjectSUICIDEen
dc.subjectGENETICSen
dc.titleRisk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B & NTRK2 polymorphismsen
dc.language.rfc3066enen
dc.rights.holderMurphy et al; licensee BioMed Central Ltd.en
dc.date.updated2015-11-03T17:03:47Zen
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