Joshua Backman
A5086605628- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Antiplatelet Therapy and Cardiovascular Diseases
- Genetic Mapping and Diversity in Plants and Animals
- Cardiomyopathy and Myosin Studies
- Lipoproteins and Cardiovascular Health
- Genetic and phenotypic traits in livestock
- Cardiovascular Function and Risk Factors
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- BRCA gene mutations in cancer
- SARS-CoV-2 and COVID-19 Research
- Diabetes Treatment and Management
- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- COVID-19 Clinical Research Studies
- Genomic variations and chromosomal abnormalities
- Platelet Disorders and Treatments
- Nutrition, Genetics, and Disease
- RNA Research and Splicing
- interferon and immune responses
- PARP inhibition in cancer therapy
- Cell Adhesion Molecules Research
- Cerebrovascular and genetic disorders
- Liver Disease Diagnosis and Treatment
Regeneron (United States)
2018-2025
Division of Program Coordination Planning and Strategic Initiatives
2022
University of Maryland, Baltimore
2015-2020
Cancer Institute (WIA)
2017
Science Applications International Corporation (United States)
2017
National Cancer Institute
2017
United States Department of Veterans Affairs
2017
University of Baltimore
2015
Abstract A major goal in human genetics is to use natural variation understand the phenotypic consequences of altering each protein-coding gene genome. Here we used exome sequencing 1 explore protein-altering variants and their 454,787 participants UK Biobank study 2 . We identified 12 million coding variants, including around loss-of-function 1.8 deleterious missense variants. When these were tested for association with 3,994 health-related traits, found 564 genes trait associations at P ≤...
The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world
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...
SUMMARY The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world. Here we describe first tranche large-scale exome sequence 49,960 participants, revealing approximately 4 million coding variants (of which ~98.4% have frequency < 1%). includes 231,631 predicted loss function variants, >10-fold increase compared to imputed same participants. Nearly all genes (>97%) had ≥1...
Abstract Aims Clopidogrel is prescribed for the prevention of atherothrombotic events. While investigations have identified genetic determinants inter-individual variability in on-treatment platelet inhibition (e.g. CYP2C19*2), evidence that these variants clinical utility to predict major adverse cardiovascular events (CVEs) remains controversial. Methods and results We assessed impact 31 candidate gene polymorphisms on adenosine diphosphate (ADP)-stimulated reactivity 3391...
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
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.
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...
Antiplatelet response to clopidogrel shows wide variation, and poor is correlated with adverse clinical outcomes. CYP2C19 loss‐of‐function alleles play an important role in this response, but account for only a small proportion of variability clopidogrel. An aim the International Clopidogrel Pharmacogenomics Consortium (ICPC) identify other genetic determinants pharmacodynamics response. A genomewide association study (GWAS) was performed using DNA from 2,750 European ancestry individuals,...
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 SARS-CoV-2 enters host cells by binding angiotensin-converting enzyme 2 (ACE2). Through a genome-wide association study, we show that rare variant (MAF = 0.3%, odds ratio 0.60, P =4.5x10 -13 ) down-regulates ACE2 expression reduces risk of COVID-19 disease, providing human genetics support for the hypothesis levels influence risk. Further, common genetic variants define score predicts severe disease among cases.
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...
A major challenge in genetic association studies is that most associated variants fall the non-coding part of human genome. We searched for with bone mineral density (BMD) after enriching discovery cohort loss-of-function (LoF) mutations by sequencing a subset Nord-Trøndelag Health Study, followed imputation remaining sample (N = 19,705), and identified ten known BMD loci. However, one previously unreported variant, LoF mutation MEPE, p.(Lys70IlefsTer26, minor allele frequency [MAF] 0.8%),...
ABSTRACT Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19), a illness that can result in hospitalization or death. We investigated associations between rare genetic variants and seven COVID-19 outcomes 543,213 individuals, including 8,248 with COVID-19. After accounting for multiple testing, we did not identify any clear either exome-wide when specifically focusing on (i) 14 interferon pathway genes which deleterious have been reported...
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 Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation. We report genome-wide association study multi-trait analysis DCM (14,256 cases) three left ventricular traits (36,203 UK Biobank participants). identified 80 genomic risk loci prioritized 62 putative effector genes, including several with rare variant associations ( MAP3K7 , NEDD4L SSPN ). Using single-nucleus transcriptomics, we identify cellular states, biological pathways, intracellular...