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.
Highlights
Suicidal behavior encompasses a spectrum ranging from the suicidal thoughts to suicide attempts and completed suicide [1]
Balanced and/or unbalanced chromosomal rearrangements including AUTS2 were found in other cases of autism [16,17,18] as well as mental retardation [19], epilepsy [20], dyslexia [13] and attention deficit hyperactivity disorder (ADHD) [21]
The information about clinical variables, such as age, gender, suicide method, blood ethanol concentration, psychiatric diagnosis and history of addiction was collected from the post-mortem medical and forensic examination protocols
Summary
Suicidal behavior encompasses a spectrum ranging from the suicidal thoughts to suicide attempts and completed suicide [1]. There is considerable evidence for contribution of genetic factors in suicidal behavior, both from twin [2,3], family [4,5] and molecular studies [6,7]. The function of AUTS2 is not known, it has been implicated in neurobehavioral disorders [13]. AUTS2 was first associated with autism by studies of monozygotic twin pairs with an identical balanced translocation [14,15]. Balanced and/or unbalanced chromosomal rearrangements including AUTS2 were found in other cases of autism [16,17,18] as well as mental retardation [19], epilepsy [20], dyslexia [13] and attention deficit hyperactivity disorder (ADHD) [21]
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