A5074696127- Genetic Associations and Epidemiology
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Monoclonal and Polyclonal Antibodies Research
- Bioinformatics and Genomic Networks
- Genetic Mapping and Diversity in Plants and Animals
- Diagnosis and Treatment of Venous Diseases
- Liver Disease Diagnosis and Treatment
- RNA modifications and cancer
- Genetic and phenotypic traits in livestock
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Lipid metabolism and disorders
- Pancreatitis Pathology and Treatment
- Medical and Biological Sciences
- Pancreatic and Hepatic Oncology Research
- Osteoarthritis Treatment and Mechanisms
- Venous Thromboembolism Diagnosis and Management
- Hip disorders and treatments
- Metabolomics and Mass Spectrometry Studies
- Cardiovascular Disease and Adiposity
- Ubiquitin and proteasome pathways
- Neuroendocrine Tumor Research Advances
- Birth, Development, and Health
- Genetics, Aging, and Longevity in Model Organisms
- Diabetes and associated disorders
Lomonosov Moscow State University
2023-2024
Human Technopole
2024
Institute of Cytology and Genetics
2014-2023
Novosibirsk State University
2014-2022
Siberian Branch of the Russian Academy of Sciences
2016-2022
Russian Academy of Sciences
2020
Abstract Aging populations face diminishing quality of life due to increased disease and morbidity. These challenges call for longevity research focus on understanding the pathways controlling healthspan. We use data from UK Biobank (UKB) cohort observe that risks major chronic diseases exponentially double every eight years, i.e., at a rate compatible with Gompertz mortality law. Assuming aging drives acceleration in morbidity rates, we build risk model predict age end healthspan depending...
Effector functions of immunoglobulin G (IgG) are regulated by the composition a glycan moiety, thus affecting activity immune system. Aberrant glycosylation IgG has been observed in many diseases, but little is understood about underlying mechanisms. We performed genome-wide association study N-glycosylation (
Joint modeling of a number phenotypes using multivariate methods has often been neglected in genome-wide association studies and if used, replication not sought. Modern omics technologies allow characterization functional phenomena large related phenotype measures, which can benefit from such joint analysis. Here, we report 23 immunoglobulin G (IgG) N-glycosylation phenotypes. In the discovery cohort, our multi-phenotype method uncovers ten significant loci, five are novel (IGH, ELL2,...
Varicose veins of lower extremities (VVs) are a common multifactorial vascular disease. Genetic factors underlying VVs development remain largely unknown. Here we report the first large-scale study performed on freely available genetic data 408,455 European-ancestry individuals. We identified 12 reliably associated loci that explain 13% SNP-based heritability, and prioritized most likely causal genes CASZ1, PIEZO1, PPP3R1, EBF1, STIM2, HFE, GATA2, NFATC2, SOX9. VVs-associated variants within...
Abstract Chronic musculoskeletal pain affects all aspects of human life. However, mechanisms its genetic control remain poorly understood. Genetic studies are complicated by the high complexity and heterogeneity phenotypes. Here, we apply principal component analysis to reduce phenotype chronic at four locations: back, neck/shoulder, hip, knee. Using matrices covariances, constructed genetically independent phenotypes (GIPs) with leading GIP (GIP1) explaining 78.4% variance analyzed...
Background and objectives Chronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia complex trait with poorly understood pathogenesis. CWP heritable (48%–54%), but its genetic architecture unknown candidate gene studies have produced inconsistent results. We conducted genome-wide association study to get insight into the background CWP. Methods Northern Europeans from UK Biobank comprising 6914 cases reporting all over body lasting >3 months 242 929 controls were studied....
Glycosylation is a common post-translational modification of proteins. associated with number human diseases. Defining genetic factors altering glycosylation may provide basis for novel approaches to diagnostic and pharmaceutical applications. Here we report genome-wide association study the blood plasma N-glycome composition in up 3811 people measured by Ultra Performance Liquid Chromatography (UPLC) technology. Starting 36 original traits UPLC, computed an additional 77 derived leading...
ZIP8 is a metal transporter with role in manganese (Mn) homeostasis. A common genetic variant (rs13107325; A391T) ranks the top 10 of pleiotropic SNPs identified GWAS; A391T has associations an increased risk schizophrenia, obesity, Crohn's disease, and reduced blood Mn. Here, we used CRISPR/Cas9-mediated knockin (KI) to generate mouse model (Zip8 393T-KI mice). Recapitulating SNP association Mn, Mn was Zip8 mice. There restricted abnormal tissue homeostasis, decreases liver kidney...
Abstract Post-translational modifications diversify protein functions and dynamically coordinate their signalling networks, influencing most aspects of cell physiology. Nevertheless, genetic regulation or influence on complex traits is not fully understood. Here, we compare the same PTM two proteins – glycosylation transferrin immunoglobulin G (IgG). By performing genome-wide association analysis glycosylation, identify 10 significantly associated loci, 9 which were reported previously....
Abstract Human protein glycosylation is a complex process, and its in vivo regulation poorly understood. Changes patterns are associated with many human diseases conditions. Understanding the biological determinants of glycome provides basis for future diagnostic therapeutic applications. Genome-wide association studies (GWAS) allow to study biology via hypothesis-free search loci genetic variants trait interest. Sixteen were identified by three previous GWAS plasma proteome N-glycosylation....
<ns4:p>To raise the power of genome-wide association studies (GWAS) and avoid false-positive results in structured populations, one can rely on mixed model based tests. When large samples are used, when multiple traits to be studied ’omics’ context, this approach becomes computationally challenging. Here we consider problem mixed-model GWAS for arbitrary number traits, demonstrate that analysis single-trait multiple-trait scenarios different computational algorithms optimal. We implement...
Most human-secreted and membrane-bound proteins have covalently attached oligosaccharide chains or glycans. Glycosylation influences the physical chemical properties of proteins, as well their biological functions. Unsurprisingly, alterations in protein glycosylation been implicated a growing number human diseases, glycans are increasingly being considered potential therapeutic targets, an essential part therapeutics, biomarkers. Although pathways biochemically well-studied, little is known...
The N-glycosylation of immunoglobulin G (IgG) affects its structure and function. It has been demonstrated that IgG patterns are inherited as complex quantitative traits. Genome-wide association studies identified loci harboring genes encoding enzymes directly involved in protein glycosylation well likely to be regulation biochemical pathways. Many these could linked immune functions risk inflammatory autoimmune diseases. aim the present study was discover replicate new associated with...
Abstract Background Genome-wide association studies have identified hundreds of loci that influence a wide variety complex human traits; however, little is known regarding the biological mechanism action these loci. The recent accumulation functional genomics (“omics”), including metabolomics data, has created new opportunities for studying role specific changes in genome. Functional genomic data are characterized by their high dimensionality, presence (strong) statistical dependency between...
Hundreds of genome-wide association studies (GWAS) human traits are performed each year. The results GWAS often published in the form summary statistics. Information from statistics can be used for multiple purposes – fundamental research biology and genetics to search potential biomarkers therapeutic targets. While amount collected by scientific community is rapidly increasing, use this data limited lack generally accepted standards. In particular, researchers who would like their have...
Changes in the N-glycosylation of immunoglobulin G (IgG) are often observed pathological states, such as autoimmune, inflammatory, neurodegenerative, cardiovascular diseases and some types cancer. However, most cases, it is not clear if disease onset causes these changes, or changes IgG among risk factors for diseases. The aim this study was to investigate casual relationships between traits 12 diseases, which alterations N-glycome were previously reported, using two sample Mendelian...
We propose a novel effective framework for the analysis of shared genetic background set genetically correlated traits using SNP-level GWAS summary statistics. This called SHAHER is based on construction linear combination by maximizing proportion its variance explained factors. requires only full statistics and matrices phenotypic correlations between as inputs. Our allows both unshared factors to be effectively analyzed. tested our simulation studies, compared it with previous...
Abstract Glycans are an essential structural component of Immunoglobulin G (IgG) that modulate its structure and function. However, regulatory mechanisms behind this complex posttranslational modification not well known. Previous genome-wide association studies (GWAS) identified 29 genomic regions involved in regulation IgG glycosylation, but only a few were functionally validated. One the key functional features glycosylation is addition galactose (galactosylation). We performed GWAS...
Abstract The ever-growing genome-wide association studies (GWAS) have revealed widespread pleiotropy. To exploit this, various methods which consider variant with multiple traits jointly been developed. However, most effort has put on improving discovery power: how to replicate and interpret these discovered pleiotropic loci using multivariate yet be discussed fully. Using only publicly available single-trait GWAS summary statistics, we develop a fast flexible multi-trait framework that...
Abstract Homeostatic control of blood glucose requires different physiological responses in the fasting and post-prandial states. We reasoned that measurements under non-standardised conditions (random glucose; RG) may capture diverse glucoregulatory processes more effectively than previous genome-wide association studies (GWAS) glycaemia or after standardised loads. Through GWAS meta-analysis RG 493,036 individuals without diabetes ethnicities we identified 128 associated loci represented...
The mounting challenge of preserving the quality life in an aging population directs focus longevity science to regulatory pathways controlling healthspan. To understand nature relationship between healthspan and lifespan uncover genetic architecture two phenotypes, we studied incidence major age-related diseases UK Biobank (UKB) cohort. We observed that rates chronic increase exponentially. risk disease acquisition doubled approximately every eight years, i.e., at a rate compatible with...
The ever-growing genome-wide association studies (GWAS) have revealed widespread pleiotropy. To exploit this, various methods that jointly consider associations of a genetic variant with multiple traits been developed. Most efforts made concerning improving GWAS discovery power. However, how to replicate these discovered pleiotropic loci has yet be discussed thoroughly. Unlike single-trait scenario, multi-trait replication is not trivial considering the underlying genotype-multi-phenotype...