GWAS and polygenic risk score of severe COVID-19 in Eastern Europe.

Background: COVID-19 disease has infected more than 772 million people, leading to 7 million deaths. Although the severe course of COVID-19 can be prevented using appropriate treatments, effective interventions require a thorough research of the genetic factors involved in its pathogenesis.

Methods: We conducted a genome-wide association study (GWAS) on 7,124 individuals (comprising 6,400 controls who had mild to moderate COVID-19 and 724 cases with severe COVID-19).

Associations of the AVPR1A RS1 Microsatellite Locus with the Level of Hormones of the Anterior Pituitary Gland and Personality Traits.

The arginine vasopressin receptor gene (AVPR1A) is one of the genes affecting mental processes. The aim of this study was to search for associations of microsatellite locus RS1, which is related to the AVPR1A expression level, with the level of hormones of the anterior pituitary gland and personality traits. The study sample included Yakut men aged 18-26 years (n = 121).

Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions.

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10).

Gene pool preservation across time and space In Mongolian-speaking Oirats.

The Oirats are a group of Mongolian-speaking peoples residing in Russia, China, and Mongolia, who speak Oirat dialects of the Mongolian language. Migrations of nomadic ethnopolitical formations of the Oirats across the Eurasian Steppe during the Late Middle Ages/early Modern times resulted in a wide geographic spread of Oirat ethnic groups from present-day northwestern China in East Asia to the Lower Volga region in Eastern Europe. In this study, we generate new genome-wide and mitochondrial DNA data for present-day Oirat-speaking populations from Kalmykia in Eastern Europe, Western Mongolia, and the Xinjiang region of China, as well as Issyk-Kul Sart-Kalmaks from Central Asia, and historically related ethnic groups from Altai, Tuva, and Northern Mongolia to study the genetic structure and history of the Oirats.

Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction.

The 313-variant polygenic risk score (PRS) provides a promising tool for breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed. Here, we explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 225,105 female participants from the UK Biobank.

Non-Coding RNAs as Key Regulators in Lung Cancer.

For several decades, most lung cancer investigations have focused on the search for mutations in candidate genes; however, in the last decade, due to the fact that most of the human genome is occupied by sequences that do not code for proteins, much attention has been paid to non-coding RNAs (ncRNAs) that perform regulatory functions. In this review, we principally focused on recent studies of the function, regulatory mechanisms, and therapeutic potential of ncRNAs including microRNA (miRNA), long ncRNA (lncRNA), and circular RNA (circRNA) in different types of lung cancer.

Epigenetics of the far northern Yakutian population.

Background: Yakuts are one of the indigenous populations of the subarctic and arctic territories of Siberia characterized by a continental subarctic climate with severe winters, with the regular January average temperature in the regional capital city of Yakutsk dipping below - 40 °C. The epigenetic mechanisms of adaptation to such ecologies and environments and, in particular, epigenetic age acceleration in the local population have not been studied before.

Results: This work reports the first epigenetic study of the Yakutian population using whole-blood DNA methylation data, supplemented with the comparison to the residents of Central Russia.

miRNA Expression Patterns in Early- and Late-Stage Prostate Cancer Patients: High-Throughput Analysis.

Prostate cancer (PCa) is one of the most common types of cancer among men. To date, there have been no specific markers identified for the diagnosis and prognosis or response to treatment of this disease. Thus, there is an urgent need for promising markers, which may be fulfilled by small non-coding RNAs known as microRNAs (miRNAs).

MiRNA-146a-A Key Player in Immunity and Diseases.

miRNA-146a, a single-stranded, non-coding RNA molecule, has emerged as a valuable diagnostic and prognostic biomarker for numerous pathological conditions. Its primary function lies in regulating inflammatory processes, haemopoiesis, allergic responses, and other key aspects of the innate immune system. Several studies have indicated that polymorphisms in miRNA-146a can influence the pathogenesis of various human diseases, including autoimmune disorders and cancer.

A Combined Effect of Polygenic Scores and Environmental Factors on Individual Differences in Depression Level.

The risk of depression could be evaluated through its multifactorial nature using the polygenic score (PGS) approach. Assuming a "clinical continuum" hypothesis of mental diseases, a preliminary assessment of individuals with elevated risk for developing depression in a non-clinical group is of high relevance. In turn, epidemiological studies suggest including social/lifestyle factors together with PGS to address the "missing heritability" problem.

Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively.

Study of The Molecular Nature of Congenital Cataracts in Patients from The Volga-Ural Region.

Hereditary cataracts are characterized by significant clinical and genetic heterogeneity, which can pose challenges for early DNA diagnosis. To comprehensively address this problem, it is essential to investigate the epidemiology of the disease, perform population studies to determine the spectrum and frequencies of mutations in the responsible genes, and examine clinical and genetic correlations. Based on modern concepts, non-syndromic hereditary cataracts are predominantly caused by genetic disease forms associated with mutations in crystallin and connexin genes.

Perspective for Studying the Relationship of miRNAs with Transposable Elements.

Transposable elements are important sources of miRNA, long non-coding RNAs genes, and their targets in the composition of protein-coding genes in plants and animals. Therefore, the detection of expression levels of specific non-coding RNAs in various tissues and cells in normal and pathological conditions may indicate a programmed pattern of transposable elements' activation. This reflects the species-specific composition and distribution of transposable elements in genomes, which underlie gene regulation in every cell division, including during aging.

MicroRNA Expression Signatures in Clear Cell Renal Cell Carcinoma: High-Throughput Searching for Key miRNA Markers in Patients from the Volga-Ural Region of Eurasian Continent.

Clear cell renal cell carcinoma (ccRCC) is characterized by high molecular genetic heterogeneity, metastatic activity and unfavorable prognosis. MicroRNAs (miRNA) are 22-nucleotide noncoding RNAs that are aberrantly expressed in cancer cells and have gained serious consideration as non-invasive cancer biomarkers. We investigated possible differential miRNA signatures that may differentiate high-grade ccRCC from primary disease stages.

Exosomal MicroRNA Levels Associated with Immune Checkpoint Inhibitor Therapy in Clear Cell Renal Cell Carcinoma.

Immunotherapy with immune checkpoint inhibitors (ICIs) has shown high efficiency in clear cell renal cell carcinoma (ccRCC) treatment. However, the response to therapy among patients varies greatly. Modern studies demonstrate the high potential of exosomal miRNAs as diagnostic and prognostic markers in oncopathology.

COVID-19: Mechanisms, risk factors, genetics, non-coding RNAs and neurologic impairments.

The novel coronavirus infection (COVID-19) causes a severe acute illness with the development of respiratory distress syndrome in some cases. COVID-19 is a global problem of mankind to this day. Among its most important aspects that require in-depth study are pathogenesis and molecular changes in severe forms of the disease.

Whole Exome Sequencing Study Suggests an Impact of , and Genes on Diffuse Gastric Cancer Development.

Gastric cancer (GC) is one of the most common cancer types in the world with a high mortality rate. Hereditary predisposition for GC is not fully elucidated so far. The aim of this study was identification of possible new candidate genes, associated with the increased risk of gastric cancer development.

FANCM missense variants and breast cancer risk: a case-control association study of 75,156 European women.

Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCM confer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCM missense variants (MVs) and breast cancer risk has been postulated. In this study, we further used the BRIDGES study to test 689 FANCM MVs for association with breast cancer risk, overall and in ER-negative and TNBC subtypes, in 39,885 cases (7566 selected for family history) and 35,271 controls of European ancestry.

Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry.

Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.

Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls.