Lactase deficiency in Russia: multiethnic genetic study.

BACKGROUND: Lactase persistence-the ability to digest lactose through adulthood-is closely related to evolutionary adaptations and has affected many populations since the beginning of cattle breeding. Nevertheless, the contrast initial phenotype, lactase non-persistence or adult lactase deficiency, is still observed in large numbers of people worldwide. METHODS: We performed a multiethnic genetic study of lactase deficiency on 24,439 people, the largest in Russia to date. The percent of each population group was estimated according to the local ancestry inference results. Additionally, we calculated frequencies of rs4988235 GG genotype in Russian regions using the information of current location and birthplace data from the client's questionnaire. RESULTS: The attained results show that among all studied population groups, the frequency of GG genotype in rs4988235 is higher than the average in the European populations. In particular, the prevalence of lactase deficiency genotype in the East Slavs group was 42.8% (95% CI: 42.1-43.4%). We also investigated the regional prevalence of lactase deficiency based on the current place of residence. CONCLUSIONS: Our study emphasizes the significance of genetic testing for diagnostics, i.e., specifically for lactose intolerance parameter, as well as the scale of the problem of lactase deficiency in Russia which needs to be addressed by the healthcare and food sectors.

Association of common genetic variants with body mass index in Russian population.

BACKGROUND: Overweight is the scourge of modern society and a major risk factor for many diseases. For this reason, understanding the genetic component predisposing to high body mass index (BMI) seems to be an important task along with preventive measures aimed at improving eating behavior and increasing physical activity. METHODS: We analyzed genetic data of a European cohort (n = 21,080, 47.25% women, East Slavs ancestry >80%) for 5 frequently found genes in the context of association with obesity: IPX3 (rs3751723), MC4R (rs17782313), TMEM18 (rs6548238), PPARG (rs1801282) and FTO (rs9939609). RESULTS: Our study revealed significant associations of FTO (rs9939609) (ß = 0.37 (kg/m2)/allele, p = <2 × 10-16), MC4R (rs17782313) (ß = 0.28 (kg/m2)/allele, p = 5.79 × 10-9), TMEM18 (rs6548238) (ß = 0.29 (kg/m2)/allele, p = 2.43 × 10-8) with BMI and risk of obesity. CONCLUSIONS: The results confirm the contribution of FTO, M4CR, and TMEM18 genes to the mechanism of body weight regulation and control.

GWAS of depression in 4,520 individuals from the Russian population highlights the role of MAGI2 (S-SCAM) in the gut-brain axis.

We present the results of the depression Genome-wide association studies study performed on a cohort of Russian-descent individuals, which identified a novel association at chromosome 7q21 locus. Gene prioritization analysis based on already known depression risk genes indicated MAGI2 (S-SCAM) as the most probable gene from the locus and potential susceptibility gene for the disease. Brain and gut expression patterns were the main features highlighting functional relatedness of MAGI2 to the previously known depression risk genes. Local genetic covariance analysis, analysis of gene expression, provided initial suggestive evidence of hospital anxiety and depression scale and diagnostic and statistical manual of mental disorders scales having a different relationship with gut-brain axis disturbance. It should be noted, that while several independent methods successfully in silico validate the role of MAGI2, we were unable to replicate genetic association for the leading variant in the MAGI2 locus, therefore the role of rs521851 in depression should be interpreted with caution.

Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. METHODS: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). FINDINGS: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. INTERPRETATION: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. FUNDING: Funded by Roche Sequencing Solutions, Inc.

COMICS: Cartoon Visualization of Omics Data in Spatial Context Using Anatomical Ontologies.

COMICS is an interactive and open-access web platform for integration and visualization of molecular expression data in anatomograms of zebrafish, carp, and mouse model systems. Anatomical ontologies are used to map omics data across experiments and between an experiment and a particular visualization in a data-dependent manner. COMICS is built on top of several existing resources. Zebrafish and mouse anatomical ontologies with their controlled vocabulary (CV) and defined hierarchy are used with the ontoCAT R package to aggregate data for comparison and visualization. Libraries from the QGIS geographical information system are used with the R packages "maps" and "maptools" to visualize and interact with molecular expression data in anatomical drawings of the model systems. COMICS allows users to upload their own data from omics experiments, using any gene or protein nomenclature they wish, as long as CV terms are used to define anatomical regions or developmental stages. Common nomenclatures such as the ZFIN gene names and UniProt accessions are provided additional support. COMICS can be used to generate publication-quality visualizations of gene and protein expression across experiments. Unlike previous tools that have used anatomical ontologies to interpret imaging data in several animal models, including zebrafish, COMICS is designed to take spatially resolved data generated by dissection or fractionation and display this data in visually clear anatomical representations rather than large data tables. COMICS is optimized for ease-of-use, with a minimalistic web interface and automatic selection of the appropriate visual representation depending on the input data.