Deep learning captures the effect of epistasis in multifactorial diseases.

Background: Polygenic risk score (PRS) prediction is widely used to assess the risk of diagnosis and progression of many diseases. Routinely, the weights of individual SNPs are estimated by the linear regression model that assumes independent and linear contribution of each SNP to the phenotype. However, for complex multifactorial diseases such as Alzheimer's disease, diabetes, cardiovascular disease, cancer, and others, association between individual SNPs and disease could be non-linear due to epistatic interactions.

[Online phenotypes of depression symptoms are associated with polygenic risk scores of somatic diseases in a population-based cohort].

Objective: To test an associations of online phenotypes of depressive symptoms with polygenic risk scores (PRS) for selected somatic diseases in a population-based cohort.

Material And Methods: Participants in a Russian population-based cohort (=4520) underwent online phenotyping based on the originally developed questionnaire using DSM-5 criteria (DSM phenotypes) and the Hospital Anxiety and Depression Scale (HADS) questionnaire (HADS phenotypes). After DNA genotyping with microarrays, PRS were calculated using summary statistics from large-scale GWASs (mostly from UK Biobank) for irritable bowel syndrome (IBS), coronary heart disease (narrow and broad phenotypes) (CHD), ischemic stroke (IS),diabetes mellitus type 2 (DT2) and migraine (MG).

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).

Genetic Associations of Anhedonia: Insights into Overlap of Mental and Somatic Disorders.

Background: Anhedonia is characterized by a reduced ability to anticipate, experience, and/or learn about pleasure. This phenomenon has a transdiagnostic nature and is one of the key symptoms of mood disorders, schizophrenia, addictions, and somatic conditions.

Aim: To evaluate the genetic architecture of anhedonia and its overlap with other mental disorders and somatic conditions.

Multiomics Picture of Obesity in Young Adults.

Obesity is a socially significant disease that is characterized by a disproportionate accumulation of fat. It is also associated with chronic inflammation, cancer, diabetes, and other comorbidities. Investigating biomarkers and pathological processes linked to obesity is especially vital for young individuals, given their increased potential for lifestyle modifications.

A case of Joubert syndrome caused by novel compound heterozygous variants in the gene.

Joubert syndrome (JS) is a recessive disorder that is characterized by midbrain-hindbrain malformation and shows the "molar tooth sign" on magnetic resonance imaging. Mutations in 40 genes, including Abelson helper integration site 1 (), inositol polyphosphate-5-phosphatase (), coiled-coil and c2 domain-containing protein 2A (), and ARL2-like protein 1 (), can cause JS. Classic JS is a part of a group of diseases associated with JS, and its manifestations include various neurological signs such as skeletal abnormalities, ocular coloboma, renal disease, and hepatic fibrosis.

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.

[Association of depression and anxiety with somatic diseases: negative lifestyle factors impact].

Objective: To assess the associations of various depression and anxiety phenotypes with manifestations of different somatic disorders and negative lifestyle factors.

Material And Methods: The study involved 5116 people. In the online questionnaire, participants provided information about age, sex, height and weight, as well as a history of smoking, alcohol use, physical activity and diagnoses/symptoms of various physical diseases.

[Anhedonia in mood disorders and somatic diseases: results of exploratory Mendelian randomization analysis].

Objective: To conduct an exploratory Mendelian randomization analysis of the causal relationships of anhedonia with a wide range of psychiatric and somatic phenotypes based on the genetic data of participants in a population study.

Material And Methods: This cross-sectional study included 4520 participants, of which 50.4% (=2280) were female.

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.

GWAS of depression in 4,520 individuals from the Russian population highlights the role of () 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 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 to the previously known depression risk genes.

Novel mutation in the gene causes early-onset but slow-progressive Charcot-Marie-Tooth disease in a Russian family: a case report.

Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous group of peripheral neuropathies most of which are associated with mutations in four genes including peripheral myelin protein-22 (, myelin protein zero (), gap junction protein beta1 () and mitofusin2 (). This current case report describes the clinical and genetic characteristics of a 6-year-old male proband. A physical examination revealed muscular hypotonia.

Screening of Depressive Symptoms in a Russian General Population Sample: A Web-based Cross-sectional Study.

Background And Objective: Web-based screening of depressive symptoms in general non-clinical population can provide better insights into actual prevalence of depressive symptoms and associated risk factors. To study the current prevalence of depressive symptoms in Russian non-clinical population we conducted screening using an online survey based on Depression subscale of Hospital Anxiety and Depression Scale (HADS-D).

Methods: The online survey covered 2610 Russian-speaking respondents and included HADS-D, questions about sex, age and presence of cardiovascular diseases (CVD) diagnoses or symptoms in respondents.

Non-linear interaction between physical activity and polygenic risk score of body mass index in Danish and Russian populations.

Body mass index (BMI) is a highly heritable polygenic trait. It is also affected by various environmental and behavioral risk factors. We used a BMI polygenic risk score (PRS) to study the interplay between the genetic and environmental factors defining BMI.

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.

Genome assembly using quantum and quantum-inspired annealing.

Recent advances in DNA sequencing open prospects to make whole-genome analysis rapid and reliable, which is promising for various applications including personalized medicine. However, existing techniques for de novo genome assembly, which is used for the analysis of genomic rearrangements, chromosome phasing, and reconstructing genomes without a reference, require solving tasks of high computational complexity. Here we demonstrate a method for solving genome assembly tasks with the use of quantum and quantum-inspired optimization techniques.

[GWAS-based polygenic risk scores for depression with clinical validation: methods and study design in the Russian population].

Depression is one of the leading causes of decreased quality of life and social functioning of patients. In the context of preventive medicine, the prevention of depression becomes a priority. To achieve the goals of prevention, it is necessary to identify specific population risk groups - individuals with a high genetic risk of depression.

ClassifyCNV: a tool for clinical annotation of copy-number variants.

Copy-number variants (CNVs) are an important part of human genetic variation. They can be benign or can play a role in human disease by creating dosage imbalances and disrupting genes and regulatory elements. Accurate identification and clinical annotation of CNVs is essential, however, manual evaluation of individual CNVs by clinicians is challenging on a large scale.

Two novel PCDH19 mutations in Russian patients with epilepsy with intellectual disability limited to females: a case report.

Background: Epilepsy with intellectual disability limited to females (Epileptic encephalopathy, early infantile, 9; EIEE9) is a rare early infantile epileptic encephalopathy characterized by an unusual X-linked inheritance: females with heterozygous mutations are affected, while hemizygous males are not.

Case Presentation: We describe the clinical and molecular characteristics of 2 Russian patients with EIEE9 (females, ages 3 years and 7 years). In these patients seizures developed at the age of 3 years.

NIPT Technique Based on the Use of Long Chimeric DNA Reads.

Non-invasive prenatal testing (NIPT) for aneuploidy on Chromosomes 21 (T21), 18 (T18) and 13 (T13) is actively used in clinical practice around the world. One of the limitations of the wider implementation of this test is the high cost of the analysis itself, as high-throughput sequencing is still relatively expensive. At the same time, there is an increasing trend in the length of reads yielded by sequencers.

Neuronal ceroid lipofuscinosis in the Russian population: Two novel mutations and the prevalence of heterozygous carriers.

Background: Neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative disorders characterized by an accumulation of lipofuscin in the body's tissues. NCLs are associated with variable age of onset and progressive symptoms including seizures, psychomotor decline, and loss of vision.

Methods: We describe the clinical and molecular characteristics of four Russian patients with NCL (one female and three males, with ages ranging from 4 to 5 years).

Liddle syndrome due to a novel mutation in the γ subunit of the epithelial sodium channel (ENaC) in family from Russia: a case report.

Background: Liddle syndrome is a monogenic disease with autosomal dominant inheritance. Basic characteristics of this disease are hypertension, reduced concentration of aldosterone and renin activity, as well as increased excretion of potassium leading to low level of potassium in serum and metabolic alkalosis. The cause of Liddle syndrome is missense or frameshift mutations in SCNN1A, SCNN1B, or SCNN1G genes that encode epithelial sodium channel subunits.

[Perspectives of the use of pharmacogenetic tests in neurology and psychiatry].

The review is devoted to the analysis of the current state of pharmacogenetic research and their use in psychiatric practice. The main genes responsible for the pharmacodynamics and pharmacokinetics of drugs used in psychiatry are listed. Foreign pharmacogenetic clinical recommendations and progress on their implementation in medical practice in various countries of Europe and the USA are analyzed.

A novel elastin gene frameshift mutation in a Russian family with cutis laxa: a case report.

Background: Cutis laxa (CL) is a rare connective tissue disorder characterized by loose, redundant, inelastic and wrinkled skin. Patients develop a prematurely aged appearance. Inheritance can be autosomal dominant or autosomal recessive.