Boris Boutkov
A5055110704- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Blood Coagulation and Thrombosis Mechanisms
- Genetic and phenotypic traits in livestock
- Cancer Genomics and Diagnostics
- Genetic Mapping and Diversity in Plants and Animals
- BRCA gene mutations in cancer
- Hemophilia Treatment and Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Atrial Fibrillation Management and Outcomes
- Cardiac electrophysiology and arrhythmias
- Cardiomyopathy and Myosin Studies
- Venous Thromboembolism Diagnosis and Management
- Genetic factors in colorectal cancer
- COVID-19 Clinical Research Studies
- Glaucoma and retinal disorders
- Ear Surgery and Otitis Media
- Hearing Loss and Rehabilitation
- Machine Learning in Bioinformatics
- Aortic aneurysm repair treatments
- Otitis Media and Relapsing Polychondritis
- Receptor Mechanisms and Signaling
- Protease and Inhibitor Mechanisms
- Osteoarthritis Treatment and Mechanisms
- Cardiovascular Disease and Adiposity
Regeneron (United States)
2020-2025
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters human host cells via angiotensin-converting enzyme (ACE2) and causes disease 2019 (COVID-19). Here, through a genome-wide association study, we identify variant (rs190509934, minor allele frequency 0.2-2%) that downregulates ACE2 expression by 37% (P = 2.7 × 10-8) reduces the risk of SARS-CoV-2 infection 40% (odds ratio 0.60, P 4.5 10-13), providing genetic evidence levels influence COVID-19 risk. We also replicate...
Abstract Rare coding variants that substantially affect function provide insights into the biology of a gene 1–3 . However, ascertaining frequency such requires large sample sizes 4–8 Here we present catalogue human protein-coding variation, derived from exome sequencing 983,578 individuals across diverse populations. In total, 23% Regeneron Genetics Center Million Exome (RGC-ME) data come African, East Asian, Indigenous American, Middle Eastern and South Asian ancestry. The includes more...
The Mexico City Prospective Study is a prospective cohort of more than 150,000 adults recruited two decades ago from the urban districts Coyoacán and Iztapalapa in
Abstract Genome-wide association analysis of cohorts with thousands phenotypes is computationally expensive, particularly when accounting for sample relatedness or population structure. Here we present a novel machine learning method called REGENIE fitting whole genome regression model that orders magnitude faster than alternatives, while maintaining statistical efficiency. The naturally accommodates parallel multiple phenotypes, and only requires local segments the genotype matrix to be...
Understanding mechanisms of hepatocellular damage may lead to new treatments for liver disease, and genome-wide association studies (GWAS) alanine aminotransferase (ALT) aspartate (AST) serum activities have proven useful investigating biology. Here we report 100 loci associating with both enzymes, using GWAS across 411,048 subjects in the UK Biobank. The rare missense variant SLC30A10 Thr95Ile (rs188273166) associates largest elevation this replicates DiscovEHR study. excretes manganese...
Atrial fibrillation (AF) has a substantial genetic component. The importance of polygenic risk is well established, while the contribution rare variants to disease warrants characterization in large cohorts.
Background Five classic thrombophilias have been recognized: factor V Leiden (rs6025), the prothrombin G20210A variant (rs1799963), and protein C, S, antithrombin deficiencies. This study aimed to determine thrombotic risk of in a cohort middle-aged older adults. Methods Results Factor Leiden, protein-coding variants PROC (protein C), PROS1 S), SERPINC1 (antithrombin) anticoagulant genes were determined 29 387 subjects (born 1923-1950, 60% women) who participated Malmö Diet Cancer...
ABSTRACT Coding variants that have significant impact on function can provide insights into the biology of a gene but are typically rare in population. Identifying and ascertaining frequency such requires very large sample sizes. Here, we present largest catalog human protein-coding variation to date, derived from exome sequencing 985,830 individuals diverse ancestry serve as rich resource for studying coding variants. Individuals African, Admixed American, East Asian, Middle Eastern, South...
Abstract Sequencing of large cohorts offers an unprecedented opportunity to identify rare genetic variants and find novel contributors human disease. We used gene-based collapsing tests genes associated with glucose, HbA1c type 2 diabetes (T2D) diagnosis in 379,066 exome-sequenced participants the UK Biobank. identified associations for GCK, HNF1A PDX1 , which are known be involved Mendelian forms diabetes. Notably, we uncovered GIGYF1 a gene not previously implicated by genetics predicted...
Background Cardiometabolic diseases are highly comorbid, but their relationship with female-specific or overwhelmingly female-predominant health conditions (breast cancer, endometriosis, pregnancy complications) is understudied. This study aimed to estimate the cross-trait genetic overlap and influence of burden cardiometabolic traits on unique women. Methods Results Using electronic record data from 71 008 ancestrally diverse women, we examined relationships between 23...
Abstract Human genetic studies of smoking behavior have been thus far largely limited to common variants. Studying rare coding variants has the potential identify drug targets. We performed an exome-wide association study phenotypes in up 749,459 individuals and discovered a protective CHRNB2 , encoding β2 subunit α4β2 nicotine acetylcholine receptor. Rare predicted loss-of-function likely deleterious missense aggregate were associated with 35% decreased odds for heavily (odds ratio (OR) =...
PURPOSE Breast and ovarian tumors in germline BRCA1/2 carriers undergo allele-specific loss of heterozygosity, resulting homologous recombination deficiency (HRD) sensitivity to poly-ADP-ribose polymerase (PARP) inhibitors. This study investigated whether biallelic HRD also occur primary nonbreast/ovarian that arise carriers. METHODS A clinically ascertained cohort with a cancer was identified, including canonical (prostate pancreatic cancers) noncanonical (all other) tumor types....
Abstract Whole-genome sequencing (WGS), whole-exome (WES) and array genotyping with imputation (IMP) are common strategies for assessing genetic variation its association medically relevant phenotypes. To date, there has been no systematic empirical assessment of the yield these approaches when applied to hundreds thousands samples enable discovery complex trait signals. Using data 100 traits from 149,195 individuals in UK Biobank, we systematically compare relative studies. We find that WGS...
Glaucoma is a leading cause of blindness. Current glaucoma medications work by lowering intraocular pressure (IOP), risk factor for glaucoma, but most treatments do not directly target the pathological changes to increased IOP, which can manifest as medication resistance disease progresses. To identify physiological modulators we performed genome- and exome-wide association analysis in >129,000 individuals with IOP measurements extended these findings an risk. We report identification...
Abstract Background Up to one of every six individuals diagnosed with cancer will be a second primary in their lifetime. Genetic factors contributing the development multiple cancers, beyond known syndromes, have been underexplored. Methods To characterize genetic susceptibility we conducted pan-cancer, whole-exome sequencing study drawn from two large multi-ancestry populations (6429 cases, 165,853 controls). We created groupings cancers: (1) an overall combined set at least cancers across...
Human genomic diversity has been shaped by both ancient and ongoing challenges from viruses. The current coronavirus disease 2019 (COVID-19) pandemic caused severe acute respiratory syndrome 2 (SARS-CoV-2) had a devastating impact on population health. However, genetic evolutionary forces impacting host genes related to SARS-CoV-2 infection are not well understood. We investigated global patterns of variation signatures natural selection at relevant (angiotensin converting enzyme [ACE2],...
Abstract Whole genome sequencing (WGS), whole exome (WES), and array genotyping with imputation (IMP) are common strategies for assessing genetic variation its association medically relevant phenotypes. To date there has been no systematic empirical assessment of the yield these approaches when applied to 100,000s samples enable discovery complex trait signals. Using data 100 traits in 149,195 individuals UK Biobank, we systematically compare relative studies. We find that WGS WES combined...