Putative protective genomic variation in the Lithuanian population.

Genomic effect variants associated with survival and protection against complex diseases vary between populations due to microevolutionary processes. The aim of this study was to analyse diversity and distribution of effect variants in a context of potential positive selection. In total, 475 individuals of Lithuanian origin were genotyped using high-throughput scanning and/or sequencing technologies. Allele frequency analysis for the pre-selected effect variants was performed using the catalogue of single nucleotide polymorphisms. Comparison of the pre-selected effect variants with variants in primate species was carried out to ascertain which allele was derived and potentially of protective nature. Recent positive selection analysis was performed to verify this protective effect. Four variants having significantly different frequencies compared to European populations were identified while two other variants reached borderline significance. Effect variant in SLC30A8 gene may potentially protect against type 2 diabetes. The existing paradox of high rates of type 2 diabetes in the Lithuanian population and the relatively high frequencies of potentially protective genome variants against it indicate a lack of knowledge about the interactions between environmental factors, regulatory regions, and other genome variation. Identification of effect variants is a step towards better understanding of the microevolutionary processes, etiopathogenetic mechanisms, and personalised medicine.

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

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.