Megan Shuey

Megan Shuey
Vanderbilt University | Vander Bilt · Department of Pharmacology

About

52
Publications
1,565
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205
Citations
Introduction
Additional affiliations
August 2009 - May 2012
Northern Arizona University
Position
  • Research Assistant

Publications

Publications (52)
Article
Full-text available
Background Maintaining a healthy lifestyle to reduce type 2 diabetes (T2D) risk is challenging and additional strategies for T2D prevention are needed. We evaluated several lipid control medications as potential therapeutic options for T2D prevention using tissue-specific predicted gene expression summary statistics in a two-sample Mendelian random...
Article
e24089 Background: Cisplatin is one of the most used cytotoxic drugs worldwide, but few studies have comprehensively evaluated CIS-TINN in adult-onset cancer survivors. It is critical to identify survivors with high degrees of handicap and related risk factors, as tinnitus (TINN) is strongly related to adverse health outcomes (AHO) including reduce...
Article
e24066 Background: Cisplatin treatment is used for many cancers, including testicular, ovarian, and head and neck malignancies. Cancer survivors with multiple cisplatin-related toxicities can have poor health-related quality of life (HRQOL). Identification of clinical and genetic factors that predict the risk of these neurotoxicities is critical. M...
Article
Full-text available
Purpose: Cisplatin is a critical component of first-line chemotherapy for several cancers, but causes peripheral sensory neuropathy, hearing loss, and tinnitus. We aimed to identify comorbidities for cisplatin-induced neurotoxicities among large numbers of similarly treated patients without the confounding effect of cranial radiotherapy. Methods:...
Article
Background: One in three Americans will have atrial fibrillation (AF) during their lifetime. Obesity and metabolic derangements are key risk factors for AF. It is unclear, however, which subset of patients would benefit most from targeted interventions aimed at weight loss and control of metabolic derangements to prevent incident AF. Methods: A lan...
Preprint
Background People hospitalized with COVID-19 often exhibit hematological alterations, such as lower lymphocyte and platelet counts, which have been reported to associate with disease prognosis. It is unclear whether inter-individual variability in baseline hematological parameters prior to acute infection influences risk of SARS-CoV-2 infection and...
Preprint
African Americans (AAs) experience a high burden of hypertension but have been underrepresented in genetic studies of blood pressure. We performed common and rare variant genome-wide association studies (GWAS) of systolic (SBP) and diastolic (DBP) blood pressure, pulse pressure and hypertension in 95,457 AAs from the Million Veteran Program and Con...
Preprint
Full-text available
To enable large-scale application of polygenic risk scores in a computationally efficient manner we translate a widely used polygenic risk score construction method, Polygenic Risk Score – Continuous Shrinkage (PRS-CS), to the Julia programing language, PRS.jl. On nine different traits with varying genetic architectures, we demonstrate that PRS.jl...
Article
Objective Animal models of atherosclerosis are used extensively to interrogate molecular mechanisms in serial fashion. We tested whether a novel systems biology approach to integration of preclinical data identifies novel pathways and regulators in human disease. Approach and Results Of 716 articles published in ATVB from 1995 to 2019 using the ap...
Article
Hypertension is estimated to affect more than 49.6% of US adults 20 years and older. Of those individuals with hypertension, more than ten million are classified as apparent treatment resistant hypertensive (aTRH). The attributable risk of uncontrolled hypertension was estimated to be 49% for cardiovascular disease and 62% for stroke. We developed...
Article
Apparent treatment-resistant hypertension (ATRH) has been linked to end-stage kidney disease (ESKD) and cardiovascular disease. We tested the hypothesis that the effect of ATRH on ESKD is greater in Black patients than in White patients and investigated the effect of ATRH on ESKD independent of APOL1 genotype. In a retrospective cohort of 139 685 h...
Article
Full-text available
Objective Body mass index (BMI) is the most commonly used predictor of weight-related comorbidities and outcomes. However, the presumed relationship between height and weight intrinsic to BMI may introduce bias with respect to prediction of clinical outcomes. A series of analyses comparing the performance of models representing weight and height as...
Article
12063 Background: Platinum levels are measurable in the serum for decades after cisplatin therapy and higher levels may be related to chemotherapy-induced toxicities. Since cisplatin is cleared exclusively by the kidney, we hypothesized that a genetic predictor of kidney function, an estimated glomerular filtration rate polygenic risk score (eGFR P...
Article
Observational studies exploring whether there is a nonlinear effect of blood pressure on cardiovascular disease (CVD) risk are hindered by confounding. This limitation can be overcome by leveraging randomly allocated genetic variants in nonlinear Mendelian randomization analyses. Based on their association with blood pressure traits in a genome-wid...
Preprint
Objective Body mass index (BMI) is the most commonly used predictor of weight-related comorbidities and outcomes. However, the presumed relationship between height and weight intrinsic to BMI may introduce bias with respect to prediction of clinical outcomes. Using Vanderbilt University Medical Center’s deidentified electronic health records and la...
Article
Given the coronavirus disease 2019 (COVID-19) pandemic, investigations into host susceptibility to infectious diseases and downstream sequelae have never been more relevant. Pneumonia is a lung disease that can cause respiratory failure and hypoxia and is a common complication of infectious disease, including COVID-19. Few genome-wide association s...
Article
Dipeptidyl peptidase‐4 (DPP‐4) inhibitors increase endogenous glucagon‐like peptide‐1 (GLP‐1). We hypothesized that genetic variation in the gene encoding the GLP‐1 receptor (GLP1R) could affect the metabolic response to DPP‐4 inhibition. To evaluate the relationship between the GLP1R rs6923761 variant (G‐to‐A nucleic acid substitution) and metabol...
Article
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Left ventricular (LV) mass is a prognostic biomarker for incident heart disease and all-cause mortality. Large-scale genome-wide association studies have identified few SNPs associated with LV mass. We hypothesized that a polygenic discovery approach using LV mass measurements made in a clinical population would identify risk factors and diseases a...
Article
Full-text available
Objective Identify blood pressure (BP) response to spironolactone in patients with apparent therapy-resistant hypertension (aTRH) using electronic medical records (EMRs) in order to estimate response in a real-world clinical setting. Design Developed an algorithm to determine BP and electrolyte response to spironolactone for use in a retrospective...
Article
Background: Vascular endothelial growth factor inhibition (VEGFi) is commonly used in the treatment of cancer. One common side effect of VEGFi therapy is elevated blood pressure. Evidence suggests the renin-angiotensin- aldosterone system (RAAS) may be involved in VEGFi mediated increases in blood pressure. Objectives: We therefore postulate that...
Article
We and others have demonstrated that interleukin-17A (IL-17A) plays a critical role in the pathogenesis of cardiovascular disease and hypertension. Patients with psoriasis, an IL-17A mediated autoimmune disease, are at elevated risk for cardiovascular events. New biologic therapies for psoriasis have been developed that target IL-17A (secukinumab)...
Article
Background: Blood pressure visit-to-visit variability is a novel risk factor for deleterious long-term cardiac and renal outcomes in the general population. We hypothesized that patients with systemic lupus erythematosus (SLE) have greater blood pressure visit-to-visit variability than control subjects and that blood pressure visit-to-visit variab...
Article
Full-text available
Given the chemoattractant potential of complement factor 5 (C5) and its increased expression in adipose tissue (AT) of obese mice, we determined whether this protein of the innate immune system impacts insulin action. C5 control (C5cont) and spontaneously C5 deficient (C5def, B10.D2-Hc0 H2d H2-T18c/oSnJ) mice were placed on low and high fat diets t...
Article
Objectives To compare the risk of resistant hypertension (RHTN) in systemic lupus erythematosus (SLE) patients and controls without SLE; to define factors associated with RHTN in SLE patients. Methods We studied 1,044 SLE patients and 5,241 control subjects using de‐identified electronic health records from a tertiary care center. SLE was defined...
Conference Paper
Introduction: Vascular endothelial growth factor inhibition (VEGFi) in cancer treatment is associated with hypertension. Imbalance between the renin-angiotensin-aldosterone system (RAAS) and VEGF may contribute to VEGFi associated hypertension. We hypothesized that RAAS blockade at the time of VEGFi attenuates increases in blood pressure. Methods:...
Article
Tizanidine, a widely used muscle relaxant that can lower blood pressure, is metabolized by the cytochrome P450 1A2 (CYP1A2). We studied 1,626 patients prescribed tizanidine and 5,012 prescribed cyclobenzaprine concurrently with a strong CYP1A2 inhibitor. The primary outcome was severe hypotension, defined as systolic blood pressure (SBP)≤70 mm Hg d...
Article
Spironolactone is a recommended add-on therapy for BP control in patients with resistant hypertension (RH). We hypothesized that we could use electronic medical records (EMR) to assess the BP response to the addition of spironolactone in patients with apparent RH who were on a stable anti-hypertensive regimen of at least three antihypertensive medi...
Article
We previously showed that abatacept, an inhibitor of T cell co-stimulation, prevents and reverses experimental hypertension. We now investigated whether it lowers blood pressure (BP) in humans. Of 1624 subjects receiving this drug in our de-identified electronic health record, 320 had hypertension and adequate baseline and follow up data (1 month t...
Article
Full-text available
Increased expression of cytochrome P450 CYP2C9, together with elevated levels of its products epoxyeicosatrienoic acids (EETs), is associated with aggressiveness in cancer. Cytochrome P450 variants CYP2C9*2 and CYP2C9*3 encode proteins with reduced enzymatic activity, and individuals carrying these variants metabolize drugs more slowly than individ...
Article
Full-text available
Objective To identify patients with hypertension with resistant and controlled blood pressure (BP) using electronic health records (EHRs) in order to elucidate practices in the real-world clinical treatment of hypertension and to enable future genetic studies. Design Using EHRs, we developed and validated algorithms to identify patients with resis...
Conference Paper
Background Resistant hypertension (RHTN) is characterised by blood pressure that remains ≥140/90 mmHg despite concurrent use of 3 antihypertensive drugs. In the general population, RHTN is associated with a 47% increased risk of cardiovascular events.¹Patients with systemic lupus erythematosus (SLE) have increased cardiovascular risk; however, no r...
Conference Paper
http://acrabstracts.org/abstract/resistant-hypertension-is-associated-with-inflammation-renal-function-and-increased-mortality-in-patients-with-systemic-lupus-erythematosus/
Article
Using Vanderbilt University Medical Center’s electronic health record (EHR), we tested the hypothesis that we could identify patients with resistant hypertension (RH) and patterns of treatment of RH in a real-world clinical setting. Patients were identified as having RH if they had blood pressure (BP) >140/90 mmHg despite concurrent treatment with...
Article
Full-text available
Context Patients with diabetes often have co-morbidities such as hypertension. It is not known how individual characteristics influence the response to dipeptidyl peptidase-4 (DPP4) inhibitors. Objective We tested the hypothesis that individual characteristics, sitagliptin dose, and genetic variability in DPP4 influence DPP4 activity during sitagl...
Article
Full-text available
Twenty to thirty percent of patients undergoing cardiac surgery develop acute kidney injury (AKI). In mice, inhibition of soluble epoxide hydrolase (sEH) attenuates renal injury following ischemia-reperfusion. We tested the hypothesis that functional variants of EPHX2, encoding sEH, are associated with AKI after cardiac surgery. We genotyped patien...
Data
Baseline plasma DiHOME/EpOME ratio, a measure of soluble epoxide hydrolase activity, and epoxyeicosatrienoic acids (EETs) concentrations in patients who did or did not develop acute kidney injury (AKI). Data are presented as median (interquartile range) unless otherwise indicated. (PDF)
Data
Characteristics of the discovery cohort according to DNA availability. Data are presented as mean (95% confidence interval) unless otherwise indicated. Abbreviations: AKI, acute kidney injury; BMI, body mass index; eGFR, estimated glomerular filtration rate; CABG, coronary artery bypass grafting; CPB, cardio-pulmonary bypass; min, minutes. (PDF)
Data
Multivariable logistic regression model for acute kidney injury (AKI) in whites with baseline eGFR < 60 mL/min/1.73m2 in the discovery cohort. Abbreviations: BMI, body mass index; eGFR, estimated glomerular filtration rate; CPB, cardio-pulmonary bypass. (PDF)
Article
Underlying mutation rates and other evolutionary forces shape the population structure of bacteria in nature. Although easily overlooked, similar forces are at work in the laboratory and may influence observed mutations. Here, we investigated tissue samples and Yersinia pestis isolates from a rodent laboratory challenge with strain CO92 using whole...
Article
Dipeptidyl peptidase IV (DPP4) inhibitors are a class of oral antihyperglycemic agents commonly used to treat type 2 diabetes mellitus (T2DM). Evidence suggests that these medications also have cardiovascular effects. We tested the hypothesis that subject characteristics and genetic variability in DPP4 , the gene encoding DPP4, affect response to D...
Article
Full-text available
Yersinia pestis was introduced to North America around 1900 and leads to nearly 100% mortality in prairie dog (Cynomys spp.) colonies during epizootic events, which suggests this pathogen may exert a strong selective force. We characterized genetic diversity at an MHC class II locus (DRB1) in Gunnison's prairie dog (C. gunnisoni) and quantified pop...
Article
Resistant hypertension (RH) affects 8.4 to 17.4% of the hypertensive population, and is associated with an elevated risk of end-organ damage. To identify genetic or environmental factors associated with RH, we developed an algorithm to phenotype patients using electronic medical records (EMRs). We modified a previously validated algorithm for detec...
Article
Full-text available
White-nose syndrome is a fungal disease that has decimated bat populations across eastern North America. Identification of the etiologic agent, Pseudogymnoascus destructans (formerly Geomyces destructans), in environmental samples is essential to proposed management plans. A major challenge is the presence of closely related species, which are ubiq...
Conference Paper
Full-text available
Background: Systems biology represents a new approach to studying human immune responses to vaccines. We used this approach to determine if the biological pathways induced by trivalent influenza vaccination (TIV) in individual immune cell subsets are distinct from those in the pooled peripheral blood mononuclear cell (PBMC) population at early time...
Article
Abstract Prairie dogs (Cynomys spp.) are highly susceptible to Yersinia pestis, with ≥99% mortality reported from multiple studies of plague epizootics. A colony of Gunnison's prairie dogs (Cynomys gunnisoni) in the Aubrey Valley (AV) of northern Arizona appears to have survived several regional epizootics of plague, whereas nearby colonies have be...
Conference Paper
Full-text available
Systems biology represents a novel approach to comprehensively study the human immune response to vaccines at the global transcriptional and proteomic level. However, most systems vaccinology approaches utilize total PBMCs in their analyses. In this context, responses of under-represented immune cell types in the blood are potentially obscured by t...