Interactions of the GABRG2 polymorphisms and childhood trauma on suicide attempt and related traits in depressed patients

Abstract

Background: Previously, we reported that the longest variant of the GABA A receptor γ2 subunit (GABRG2) was associated with suicidal behavior. The present study therefore aimed to determine whether polymorphisms near the alternatively spliced exon of GABRG2 are associated with suicide attempt (SA) and its related traits, and how these variants might interact with reported childhood trauma (CT) in their association with suicidal behavior.

Methods: We examined 5 single nucleotide polymorphisms (SNPs) of GABRG2. Subjects were suicide Attempters (N = 94), non-suicide attempters (N = 168) with MDD or Bipolar depression, and healthy volunteers (N = 100). Data on demographics, depression severity and suicide attempts were collected. Participants also completed a set of instruments assessing CT, and lifetime aggression and impulsivity.. GABRG2 polymorphisms were genotyped using Sanger sequencing.

Results: Allele A of rs211034 was a protective factor for SA (OR = 0.50 (0.32, 0.80), p = 0.003), and had an interaction effect with emotional neglect (OR = 0.89 (0.82, 0.97), p = 0.006) on depression. One haploblock (consisting of rs211035 and rs211034) was identified within these SNPs, and subjects with haplotype GA (frequency = 7.3%), had lower rate of SA (OR=0.26(0.10, 0.67), p = 0.006). Cognitive impulsivity (OR=1.38)1.24,1.55), p < 0.001), non-planning impulsivity (OR = 1.18 (1.10,1.25), p < 0.001), anger (OR = 1.13 (1.07,1.19), p < 0.001), impulsivity total score (OR = 1.10(1.06,1.15), p < 0.001), hostility (OR = 1.10 (1.04, 1.15), p < 0.001), aggression total score (OR = 1.05 (1.03,1.07), p < 0.001) were associated with depression, meanwhile, hopelessness (OR = 2.18 (1.56, 3.04), p < 0.001) and impulsivity total score (OR = 1.05 (1.02,1.08), p < 0.001) were associated with the risk of SA, adjusted by age and gender. There was no mediation effect in the relationship among CT, gene polymorphisms and SA or depression through increased impulsivity or aggression.

Limitations: The main limitation of this study is its modest sample size. More genetic variants as well as epigenetic markers should be examined in future studies.

Conclusions: These findings add to evidence for the involvement of GABRG2 and impulsivity and hopelessness in SA independent from their association with depression. More research is needed on possible mediators of the relationship between GABA-related gene and SA.

Keywords: Childhood trauma; Gene polymorphism; Impulsivity; Suicide attempt.