Novel human genome variants associated with alcohol use disorders identified in a Lithuanian cohort

Abstract

Background.Alcohol use disorder (AUD) is a chronic relapsing brain disease characterized by compulsive alcohol use, loss of control over alcohol intake, and a negative emotional state when not using (1). Abusive alcohol consumption directly affects a person’s physical and psychological health and social life. The World Health Organization has shown that Lithuania is a leading country in pure alcohol consumption in the world (2). The aim of this study is to find novel genome variants that are associated with the AUD in the Lithuanian cohort.Materials and methods.A case-control study included 294 individuals of Lithuanian ethnicity, who were divided into two groups based on their habits of alcohol use. Single nucleotide polymorphism array analysis was performed using Illumina HiScanSQ™ genome analyzer.Results.Our study showed that rs686141T>C variant in NALCN gene is more prevalent in the non-drinker group compared to the alcohol drinker group (relative allele frequency, respectively: 0.38 and 0.27, OR = 0.60 (CI 95% 0.37–0.98), p = 0.0408). Meanwhile, rs6354C>A, in SLC6A4 gene, variant’s genotype distribution showed statistically significant difference between the non-drinker and alcohol drinker group (distribution of genotypes in the case group: 9/72/172 (CC/CA/AA) and in the control group: 5/7/29, p = 0.0264).Conclusion.We analyzed 23 genes associated with AUD and identified two novel genome variants (rs686141T>C and rs6354C>A). The study shows that genome analysis is an important tool for AUD research. The results supplement the known information about genes associated with AUD.

Sodium Leak Channel in the Nucleus Accumbens Modulates Ethanol-Induced Acute Stimulant Responses and Locomotor Sensitization in Mice: A Brief Research Report

“…NALCN is widely expressed in the central nervous system and regulates neuronal excitability ( Lu et al, 2007 ). Several studies indicated that NALCN implicated in the ethanol responses of both animals and humans being ( Speca et al, 2010 ; Cochet-Bissuel et al, 2014 ; Wetherill et al, 2014 ; Baronas et al, 2018 ). One single nucleotide polymorphism (SNP) in NALCN has been found to strongly associate with the high risk of alcohol dependence ( Wetherill et al, 2014 ).…”

“…NALCN modulates important functions such as locomotor behaviors ( Xie et al, 2013 ), respiratory rhythm ( Lu et al, 2007 ), and responsiveness to general anesthetics ( Jospin et al, 2007 ; Singaram et al, 2011 ; Ou et al, 2020 ; Yang et al, 2020 ). Previous studies reported that responses to ethanol was changed in NALCN mutations of both animals and humans ( Morgan and Sedensky, 1995 ; Speca et al, 2010 ; Wetherill et al, 2014 ; Baronas et al, 2018 ). The UNC79 heterozygous mice, which is an important auxiliary subunit of NALCN, exhibited acute hypersensitivity to and increased voluntary consumption of ethanol ( Speca et al, 2010 ), suggesting that NALCN may modulate the ethanol actions.…”