Possible Association between Suicide Committed under Influence of Ethanol and a Variant in the AUTS2 Gene

Abstract

Backgroundrs6943555 in AUTS2 has been shown to modulate ethanol consumption. We hypothesized that rs6943555 might be associated with completed suicide.MethodsWe genotyped rs6943555 in 625 completed suicides and 3861 controls using real-time TaqMan Allelic Discrimination Assay. All individuals were Polish Caucasians.ResultsWe detected an association between suicide and rs6943555 A allele (OR = 1.17, P = 0.018 for allelic comparison, OR = 1.24, P = 0.013 for dominant, and OR = 1.18, P = 0.020 for co-dominant model of inheritance). The association remained significant after adjusting for age and gender (co-dominant: P = 0.002 and dominant model: P = 0.001). After stratifying suicides according to blood ethanol concentration (BAC≤ 20 mg/dl and BAC > 20 mg/dl) the association remained significant only for cases who committed suicide under influence of alcohol (co-dominant: OR = 1.37, P = 0.004 and dominant model: OR = 1.45, P = 0.006). To validate this finding we genotyped another cohort of 132 cases. We reproduced the association between rs6943555 A allele and suicide under influence of ethanol (allelic comparison: OR = 1.55, P = 0.023; co-dominant : OR = 1.54, P = 0.031; dominant model: OR = 1.84, P = 0.015). Analyzing pooled suicides with BAC >20 mg/dl (N = 300) we found the association of rs6943555 A allele not only vs. controls (allelic OR = 1.41, P = 0.00029) but also vs. cases with BAC ≤ 20 mg/dl (N = 449, allelic OR = 1.33, P = 0.019).ConclusionsIn our study rs6943555 A allele is associated with suicide committed after drinking ethanol shortly before death. The rs6943555 A allele may be linked to adverse emotional reaction to ethanol, which could explain the association with lower consumption in general population as well as the predisposition to suicide under influence of ethanol.

The role of AUTS2 in neurodevelopment and human evolution

“…In addition, the AUTS2 locus has been shown to be implicated or altered in individuals with schizoaffective disorder [45], bipolar disorder [46,47], epilepsy [48], ADHD [49], differential processing speed [50], suicidal tendencies under the influence of alcohol [51], and dyslexia [23], either through CNV or genome-wide association studies. A 2012 article sequenced balanced chromosomal abnormalities in patients with neurodevelopmental disorders, and found the AUTS2 locus to be perturbed in individuals with microcephaly, macrocephaly, ataxia, visual impairment, language disability, seizure disorder, dysmorphic features, behavioral problems, motor delay, or Rubinstein–Taybi syndrome [24].…”

The Evidence for the Contribution of the Autism Susceptibility Candidate 2 (AUTS2) Gene in Heroin Dependence Susceptibility

“…Therefore, we aimed to identify a set of tagging SNPs that efficiently tag all the known common variants and are likely to tag most of the unknown common variants. Marker selection was based on previous studies (Chen et al 2013;Chojnicka et al 2013), and preliminary analysis was performed using the HapMap data. We examined tagSNPs in the Haploview software v4.2, using the Chinese Han in Beijing (CHB) population and a minor allele frequency (MAF) cutoff ≥5 % (the HapMap data release 27).…”

Regulation of neuronal migration, an emerging topic in autism spectrum disorders

“…) (review Edenberg and Foroud ), as well as with a risk for suicide (Chojnicka et al . ; Coon et al . ).…”