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

Abstract

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

A pilot integrative genomics study of GABA and glutamate neurotransmitter systems in suicide, suicidal behavior, and major depressive disorder

“…The allelic variability in SLC1A2 may be associated with the underlying diathesis for suicidal acts [Murphy et al, 2011]. The GABRG2 polymorphisms are associated with suicidal behavior in schizophrenia with alcohol dependence or abuse [Zai et al, 2014].…”

“…Some studies have reported an association of some variants in genes related to glutamate and GABA systems with suicidal behavior [Kertes et al, 2011; Chiesa et al, 2012; Myung et al, 2012] and MDD [Murphy et al, 2011], while other studies found no association [Sokolowski et al, 2013]. Postmortem microarray studies in suicide and/or MDD report differential expression of GABA receptor subunits, glutamate-ammonia ligase (GLUL), or glutamate receptors in prefrontal and/or limbic brain regions [Choudary et al, 2005; Kim et al, 2007; Klempan et al, 2009; Sequeira et al, 2007, 2009; Tripp et al, 2012].…”

GLAST But Not Least—Distribution, Function, Genetics and Epigenetics of l-Glutamate Transport in Brain—Focus on GLAST/EAAT1

“…Murphy et al [62] noted a weak association between suicidal behaviour and rs2269272 polymorphism. Turic et al [63] described association between ADHD and rs2269272 polymorphism.…”

Genetic Research on Sleep, Sleep Disturbances and Associated Difficulties

“…Ряд исследований, проведенных на трансгенных мышах, лишен-ных гена рецептора HTR1B, констатирует возможное вовлечение функци-ональных вариантов гена HTR1B в этиологию таких психических рас-стройств, как агрессивность и алкоголизм (Saudo et al, 1994;Brunner et al, 1999). Ряд независимых исследований подтвердил ассоциацию поли-морфных вариантов гена HTR1B с суицидальным поведением (Gaysina et al, 2003;Lappalainen et al, 1998;New et al, 2001), однако имеются рабо-ты, в которых данная ассоциация не выявлена (Wang et al, 2009;Zupanc et al, 2010;Murphy et al, 2011;Wrzosek et al, 2011).…”