A5034126524- Genetic Mapping and Diversity in Plants and Animals
- Genetic and phenotypic traits in livestock
- Acute Myeloid Leukemia Research
- Genetics and Plant Breeding
- Cancer Genomics and Diagnostics
- Otitis Media and Relapsing Polychondritis
- Hemoglobinopathies and Related Disorders
- Vasculitis and related conditions
- Gene Regulatory Network Analysis
- Hematological disorders and diagnostics
- Electrolyte and hormonal disorders
- Genomic variations and chromosomal abnormalities
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Gene expression and cancer classification
- Statistical Methods in Clinical Trials
- Blood disorders and treatments
- Congenital Ear and Nasal Anomalies
- Energy Load and Power Forecasting
- Chronic Myeloid Leukemia Treatments
- Inflammatory Myopathies and Dermatomyositis
- Advanced Clustering Algorithms Research
- Radiology practices and education
- Delphi Technique in Research
- Innovations in Educational Methods
- Genetic Associations and Epidemiology
Vanderbilt University Medical Center
2022-2025
Vanderbilt University
2025
University of North Carolina at Chapel Hill
2015-2021
The University of Texas Southwestern Medical Center
2018
Pediatrics and Genetics
2017
University of North Carolina Health Care
2016
Case Western Reserve University
2011
University of Missouri
2011
University of Iowa
2011
In this paper, we provide background and context regarding the potential for a new data-sharing platform, Project Data Sphere (PDS) initiative, funded by financial in-kind contributions from CEO Roundtable on Cancer, to transform cancer research improve patient outcomes. Given relatively modest decline in death rates over past several years, paradigm is needed accelerate therapeutic approaches oncologic diseases. Phase III clinical trials generate large volumes of potentially usable...
Somatic variants in UBA1 cause VEXAS, a recently described, systemic autoinflammatory disease. Research on VEXAS has largely focused highly symptomatic patients. We sought to determine the prevalence of canonical, VEXAS-associated somatic and their disease penetrance diverse, unselected population.
Clinical trials of tolvaptan showed it to be a promising candidate for the treatment Autosomal Dominant Polycystic Kidney Disease (ADPKD) but also revealed potential idiosyncratic drug-induced liver injury (DILI) in this patient population. To identify risk factors and mechanisms underlying DILI, 8 mice each 45 strains genetically diverse Collaborative Cross (CC) mouse population were treated with single oral dose either or vehicle. Significant elevations plasma alanine aminotransferase...
Purpose Medical podcasts have grown in popularity, but little is known about their didactic methods. This study sought to systemically describe the pedagogical approach employed by 100 most popular medical United States. also aimed assess factors related quality control and conflicts of interest podcasting.Methods The authors averaged rank positions for Apple Medicine category States from 06/01/18 09/30/20 generate a list highest-ranked podcasts. They developed validated categorization...
To develop an algorithm using routine clinical laboratory measurements to identify people at risk for systematic underestimation of glycated hemoglobin (HbA1c) due p.Val68Met glucose-6-phosphate dehydrogenase (G6PD) deficiency. We analyzed 122,307 participants self-identified Black race across four large cohorts with blood glucose, HbA1c, and red cell distribution width from a single draw. In UK Biobank, we used recursive partitioning criteria possible likely G6PD validated the in NIH All...
The study objective was to determine if a common single nucleotide polymorphism in the interleukin 6 (IL-6) receptor (rs2228145, p.Asp358Ala) predicted treatment response tocilizumab giant cell arteritis (GCA). Genetic sequencing of rs2228145 locus performed 2 independent cohorts patients with GCA. Peripheral blood mononuclear cells (PBMCs) from and controls were evaluated for expression (IL-6R) its coreceptor, gp130, using flow cytometry. same PBMCs stimulated IL-6 downstream targets IL-6:...
Abstract Mosaic chromosomal alterations of the autosomes (aut-mCAs) are large structural somatic mutations which cause clonal hematopoiesis and increase cancer risk. Here, we detected aut-mCAs in 1,011,269 participants across four biobanks. Through integrative analysis minimum critical region inherited genetic variation, found that proto-oncogenes exclusively drive gains, tumor suppressors losses, copy-neutral events can be driven by either. We identified three novel risk loci CHI3L2, HLA...
Preclinical evidence has demonstrated that common intratumor bacteria metabolize the chemotherapeutic drug gemcitabine. The significance of this bacterial metabolism pathway, relative to known metabolic pathways by host enzymes, is not known. We hypothesized clinically significant and "knockdown" antibacterial therapy unintended effect increasing effective dose gemcitabine, thereby risk for gemcitabine-associated toxicities.
Abstract Background. Mitoxantrone was approved for use in metastatic castrate-resistant prostate cancer (mCRPC) based on pain palliation without observed survival benefit a small phase III trial 1996. To re-evaluate possible benefits larger contemporary sample and to demonstrate analytic uses of the newly available Project Data Sphere online resource, we used data from control arms completed clinical trials compare toxicity among patients with postdocetaxel mCRPC treated mitoxantrone...
Idelalisib is a phosphatidylinositol 3-kinase inhibitor highly selective for the delta isoform that has shown good efficacy in treating chronic lymphocytic leukemia and follicular lymphoma. In clinical trials, however, idelalisib was associated with rare, but potentially serious liver lung toxicities. this study, we used Collaborative Cross (CC) mouse population to identify genetic factors drug response may inform risk management strategies humans. Eight male mice (4 matched pairs) from 50...
Hand impairment is a frequently reported complaint in systemic sclerosis (SSc) patients and leading cause of disability diminished quality life. Managing hand pain can be particularly challenging due to the coexistence non-inflammatory arthralgias, inflammatory arthritis, acro-osteolysis, tenosynovitis, joint contractures, tendon friction rubs, nerve entrapment, Raynaud’s phenomenon (RP), digital ulcers (DU), sclerodactyly, calcinosis, chronic pain. While physical examination radiographs are...
Sample sizes set on the basis of desired power and expected effect size are often too small to yield a confidence interval narrow enough provide precise estimate population value.Formulae presented achieve width for four common statistical tests: finding value correlation coefficient (Pearson r), mean difference between two populations (independent- dependent-samples t tests), proportions (chi-square contingency tables).Use formulae is discussed in context goals research: (a) determining...
Standard QTL mapping procedures seek to identify genetic loci affecting the phenotypic mean while assuming that all individuals have same residual variance. But when variance differs systematically between groups, perhaps due a or environmental factor, such standard can falter: in testing for associations, they attribute too much weight observations are noisy and little those precise, resulting reduced power increased susceptibility false positives. The negative effects of "background...
Clonal hematopoiesis of indeterminate potential (CHIP) is an asymptomatic condition associated with elevated risk for myeloid neoplasms (MN). Patients CHIP and cytopenia are at greater MN. Quantifying the incidence identifying factors among patients critical improving clinical management. We analyzed sequencing data from 805,249 participants in NIH All Us Research Program (AoU), Vanderbilt's BioVU repository, UK Biobank (UKB). Genetic mutations, laboratory values, MN diagnoses were included...
We present vqtl, an R package for mean-variance QTL mapping. This mapping approach tests genetic loci that influence the mean of phenotype, termed QTL, variance or some combination two, QTL. It is unique in its ability to correct heterogeneity arising not only from itself but also nuisance factors, such as sex, batch, housing. provides functions conduct genome scans, run permutations assess statistical significance, and make informative plots communicate results. Because it inter-operable...
Abstract We illustrate, through two case studies, that “mean-variance QTL mapping”—QTL mapping models effects on the mean and variance simultaneously—can discover traditional interval cannot. Mean-variance is based double generalized linear model, which extends standard model used in by incorporating not only a set of genetic covariate for but also such residual variance. Its potential use has been described previously, it remains underutilized, with certain key advantages undemonstrated...
ABSTRACT We present vqtl , an R package for mean-variance QTL mapping. This mapping approach tests genetic loci that influence the mean of phenotype, termed QTL, variance or some combination two, QTL. It is unique in its ability to correct heterogeneity arising not only from itself but also nuisance factors, such as sex, batch, housing. provides functions conduct genome scans, run permutations assess statistical significance, and make informative plots communicate results. Because it...
ABSTRACT We illustrate, through two case studies, that “mean-variance QTL mapping” can discover traditional interval mapping cannot. Mean-variance is based on the double generalized linear model, which elaborates standard model by incorporating not only a for data itself, but also residual variance. Its potential use in has been described previously, it remains underutilized, with certain key advantages undemonstrated until now. In first study, we mean-variance to reanalyze reduced...
ABSTRACT Most QTL mapping approaches seek to identify “mean QTL”, genetic loci that influence the phenotype mean, after assuming all individuals in population have equal residual variance. Recent work has broadened scope of variance, termed “variance or some combination mean and which we term “mean-variance QTL”. Even these approaches, however, fail address situations where other factor, be it an environmental factor a distant locus, influences We this situation “background variance...
Abstract Gene-gene (GxG) interactions play an important role in human genetics, potentially explaining part of the “missing heritability” polygenic traits and variable expressivity monogenic traits. Many GxG have been identified model organisms through experimental breeding studies, but they difficult to identify populations. To address this challenge, we applied two complementary variance QTL (vQTL)-based approaches that contribute blood blood-related disease risk. First, used previously...
Objective: Rheumatoid arthritis (RA) is a systemic autoimmune disease with complex pathogenesis involving the innate and adaptive immune system. Clonal hematopoiesis of indeterminate potential (CHIP) defined by clonal proliferation one hematopoietic stem cell typically asymptomatic. Both are common among older adults. CHIP associated multiple diseases, but has not been thoroughly evaluated for its relationship RA. Methods: We examined three large biobanks where status participants determined...