Medicine and Health Sciences Commons^™

Infections In The First Year Of Life And Development Of Beta Cell Autoimmunity And Clinical Type 1 Diabetes In High-Risk Individuals: The Trigr Cohort, Olga Kordonouri, David Cuthbertson, Malin Belteky, Bärbel Aschemeier-Fuchs, Neil H White, Elisabeth Cummings, Mikael Knip, Johnny Ludvigsson

2020-Current year OA Pubs

AIMS/HYPOTHESIS: Accumulated data suggest that infections in early life contribute to the development of type 1 diabetes. Using data from the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), we set out to assess whether children who later developed diabetes-related autoantibodies and/or clinical type 1 diabetes had different exposure to infections early in life compared with those who did not.

METHODS: A cohort of 2159 children with an affected first-degree relative and HLA-conferred susceptibility to type 1 diabetes were recruited between 2002 and 2007 and followed until 2017. Infections were registered prospectively. The relationship between infections in the …

Fatness, Fitness And The Aging Brain: A Cross Sectional Study Of The Associations Between A Physiological Estimate Of Brain Age And Physical Fitness, Activity, Sleep, And Body Composition, David Wing, Lisa T Eyler, Eric J Lenze, Julie Loebach Wetherell, Jeanne F Nichols, Romain Meeusen, Job G Godino, Joshua S Shimony, Abraham Z Snyder, Tomoyuki Nishino, Ginger E Nicol, Guy Nagels, Bart Roelands

2020-Current year OA Pubs

INTRODUCTION: Changes in brain structure and function occur with aging. However, there is substantial heterogeneity both in terms of when these changes begin, and the rate at which they progress. Understanding the mechanisms and/or behaviors underlying this heterogeneity may allow us to act to target and slow negative changes associated with aging.

METHODS: Using T1 weighted MRI images, we applied a novel algorithm to determine the physiological age of the brain (brain-predicted age) and the predicted age difference between this physiologically based estimate and chronological age (BrainPAD) to 551 sedentary adults aged 65 to 84 with self-reported cognitive complaint measured …

Direct Cd32 T-Cell Cytotoxicity: Implications For Breast Cancer Prognosis And Treatment, Giuseppe Sconocchia, Giulia Lanzilli, Valeriana Cesarini, Domenico A Silvestris, Katayoun Rezvani, Roberto Arriga, Sara Caratelli, Ken Chen, Jinzhuang Dou, Carlo Cenciarelli, Gabriele Toietta, Silvia Baldari, Tommaso Sconocchia, Francesca De Paolis, Anna Aureli, Giandomenica Iezzi, Maria Irno Consalvo, Francesco Buccisano, Maria I Del Principe, Luca Maurillo, Adriano Venditti, Alessio Ottaviani, Giulio C Spagnoli

Faculty, Staff and Student Publications

The FcγRII (CD32) ligands are IgFc fragments and pentraxins. The existence of additional ligands is unknown. We engineered T cells with human chimeric receptors resulting from the fusion between CD32 extracellular portion and transmembrane CD8α linked to CD28/ζ chain intracellular moiety (CD32-CR). Transduced T cells recognized three breast cancer (BC) and one colon cancer cell line among 15 tested in the absence of targeting antibodies. Sensitive BC cell conjugation with CD32-CR T cells induced CD32 polarization and down-regulation, CD107a release, mutual elimination, and proinflammatory cytokine production unaffected by human IgGs but enhanced by cetuximab. CD32-CR T cells protected immunodeficient mice …

Statistical Process Control To Monitor Use Of A Web-Based Autoplanning Tool, Hunter Mehrens, Raphael Douglas, Mary Gronberg, Kelly Nealon, Joy Zhang, Laurence Court

Faculty, Staff and Student Publications

PURPOSE: To investigate the use of statistical process control (SPC) for quality assurance of an integrated web-based autoplanning tool, Radiation Planning Assistant (RPA).

METHODS: Automatically generated plans were downloaded and imported into two treatment planning systems (TPSs), RayStation and Eclipse, in which they were recalculated using fixed monitor units. The recalculated plans were then uploaded back to the RPA, and the mean dose differences for each contour between the original RPA and the TPSs plans were calculated. SPC was used to characterize the RPA plans in terms of two comparisons: RayStation TPS versus RPA and Eclipse TPS versus RPA for …

Reorganization Of The Functional Connectome From Rest To A Visual Perception Task In Schizophrenia And Bipolar Disorder, Philipp Riedel, Junghee Lee, Christopher G Watson, Amy M Jimenez, Eric A Reavis, Michael F Green

Faculty, Staff and Student Publications

Functional connectome organization is altered in schizophrenia (SZ) and bipolar disorder (BD). However, it remains unclear whether network reorganization during a task relative to rest is also altered in these disorders. This study examined connectome organization in patients with SZ (N = 43) and BD (N = 42) versus healthy controls (HC; N = 39) using fMRI data during a visual object-perception task and at rest. Graph analyses were conducted for the whole-brain network using indices selected a priori: three reflecting network segregation (clustering coefficient, local efficiency, modularity), two reflecting integration (characteristic path length, global efficiency). Group differences were limited …

A Cross-National Comparison Of The Linkages Between Family Structure Histories And Early Adolescent Substance Use, Haley Stritzel, Michael Green, Robert Crosnoe

Faculty, Staff and Student Publications

Family structure can influence adolescent health with cascading implications into adulthood. Life course theory emphasizes how this phenomenon is dynamic across time, contextualized in policy systems, and grounded in processes of selection and socialization. This study used data from the U.S. (National Longitudinal Survey of Youth 1979 Child and Young Adults, n = 6,236) and U.K. (Millennium Cohort Study, n = 11,095) to examine associations between a single mother family structure between ages 0-14 and early adolescent substance use at age 14 across time and place, using inverse probability of treatment weighting to explore how results varied by selection into …

Radiomics In Abdominopelvic Solid-Organ Oncologic Imaging: Current Status, Xiaoyang Liu, Mohamed G Elbanan, Antonio Luna, Masoom A Haider, Andrew D Smith, Carl F Sabottke, Bradley M Spieler, Baris Turkbey, David Fuentes, Ahmed Moawad, Serageldin Kamel, Natally Horvat, Khaled M Elsayes

Faculty, Staff and Student Publications

Radiomics is the process of extraction of high-throughput quantitative imaging features from medical images. These features represent noninvasive quantitative biomarkers that go beyond the traditional imaging features visible to the human eye. This article first reviews the steps of the radiomics pipeline, including image acquisition, ROI selection and image segmentation, image preprocessing, feature extraction, feature selection, and model development and application. Current evidence for the application of radiomics in abdominopelvic solid-organ cancers is then reviewed. Applications including diagnosis, subtype determination, treatment response assessment, and outcome prediction are explored within the context of hepatobiliary and pancreatic cancer, renal cell carcinoma, prostate …

Nocturnal Ventricular Tachycardia Storm: A Man-Made Form., Jill Swinning, Andrea Robinson, Eugene Fu

Heart and Vascular Articles

No abstract provided.

Mediterranean-Style Diet And Exercise Improve Parameters For Management And Prevention Of Type 2 Diabetes Mellitus, Stefani Ann Derrick

Master's Theses

Type 2 diabetes mellitus (T2DM) is a chronic condition recognized as the inability to maintain glucose homeostasis, typically presenting with insulin resistance and systemic inflammation. With the prevalence of T2DM and major risk factors such as prediabetes and obesity increasing each year, there is a crucial need to identify strategies for the management and prevention of this condition. Addressing lifestyle-related risk factors through consumption of a well-balanced, nutritious diet and maintaining regular moderate- to high-intensity physical activity may provide a strategy for improving glycemic control, improving metrics of body composition, and decreasing the inflammatory response associated with metabolic dysregulation. Twenty-two …

A Study Of Heart Disease Diagnosis Using Machine Learning And Data Mining, Intisar Ahmed

Electronic Theses, Projects, and Dissertations

Heart disease is the leading cause of death for people around the world today. Diagnosis for various forms of heart disease can be detected with numerous medical tests, however, predicting heart disease without such tests is very difficult. Machine learning can help process medical big data and provide hidden knowledge which otherwise would not be possible with the naked eye. The aim of this project is to explore how machine learning algorithms can be used in predicting heart disease by building an optimized model. The research questions are; 1) What Machine learning algorithms are used in the diagnosis of heart …

Impact Of A Dedicated Atrial Fibrillation Clinic On Diagnosis-To-Ablation Time., Andrea Robinson, Nagesh Chopra, Auroa G Badin, Sreedhar R Billakanty, Keaira Cooper, Eugene Y Fu, Jennifer James, Victoria Murnane, Jill Swinning, Mitchell Stelzer, Jaret D Tyler, Anish K Amin

Heart and Vascular Articles

BACKGROUND: Outcomes following catheter ablation (CA) for atrial fibrillation (AF) improve as the diagnosis-to-ablation time (DAT) shortens. Use of a protocol-based integrated care model through a dedicated atrial fibrillation clinic (AFC) may serve to standardize treatment pathways and decrease DAT.

OBJECTIVE: To evaluate the DAT and clinical characteristics of patients with AF referred from an AFC vs a conventional electrophysiology clinic (EC).

METHODS: Retrospective analysis was completed in consecutive patients undergoing index AF ablation at Riverside Methodist Hospital in 2019 with minimum 1 year follow-up. Patients were categorized based off their CA referral source (AFC vs EC) and where the …

A Novel, Brief, Fully Automated Intervention To Extend The Antidepressant Effect Of A Single Ketamine Infusion: A Randomized Clinical Trial, Rebecca B Price, Crystal Spotts, Benjamin Panny, Angela Griffo, Michelle Degutis, Nicolas Cruz, Elizabeth Bell, Kevin Do-Nguyen, Meredith L Wallace, Sanjay J Mathew, Robert H Howland

Staff and Researcher Publications

Objective: Intravenous ketamine, which displays rapid antidepressant properties, is posited to reverse depression by rapidly enhancing neuroplasticity. The authors tested whether an automated, computer-based approach could efficiently leverage enhanced neuroplasticity to extend the durability of rapid clinical response.

Methods: A total of 154 adults (ages 18-60) with treatment-resistant unipolar depression were randomized in a double-blind, parallel-arm design to receive an active/active treatment combination (ketamine plus active "automated self-association training" [ASAT]; N=53) or one of two control arms that lacked either the active drug component (saline plus active ASAT; N=51) or the active behavioral component (ketamine plus sham ASAT; N=50). One …

International Pooled Patient-Level Meta-Analysis Of Ketamine Infusion For Depression: In Search Of Clinical Moderators, Rebecca B Price, Nicholas Kissel, Andrew Baumeister, Rebecca Rohac, Mary L Woody, Elizabeth D Ballard, Carlos A Zarate, William Deakin, Chadi G Abdallah, Adriana Feder, Dennis S Charney, Michael F Grunebaum, J John Mann, Sanjay J Mathew, Bronagh Gallagher, Declan M Mcloughlin, James W Murrough, Suresh Muthukumaraswamy, Rebecca Mcmillan, Rachael Sumner, George Papakostas, Maurizio Fava, Rebecca Hock, Jennifer L Phillips, Pierre Blier, Paulo Shiroma, Peter Šóš, Tung-Ping Su, Mu-Hong Chen, Mikael Tiger, Johan Lundberg, Samuel T Wilkinson, Meredith L Wallace

Children’s Nutrition Research Center Staff Publications

Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least …

Impact Of Colchicine On Mortality And Morbidity In Covid-19: A Systematic Review., Devang Sanghavi, Pankaj Bansal, Ikwinder Preet Kaur, Mohsin Sheraz Mughal, Chandana Keshavamurthy, Austin Cusick, Jennifer Schram, Siva Naga S Yarrarapu, Abhishek R Giri, Nirmaljot Kaur, Pablo Moreno Franco, Andy Abril, Fawad Aslam

Pharmacy Articles

INTRODUCTION: Colchicine, because of its anti-inflammatory and possible anti-viral properties, has been proposed as potential therapeutic option for COVID-19. The role of colchicine to mitigate "cytokine storm" and to decrease the severity and mortality associated with COVID-19 has been evaluated in many studies.

OBJECTIVE: To evaluate the role of colchicine on morbidity and mortality in COVID-19 patients.

METHODS: This systematic review was conducted in accordance with the PRISMA recommendations. The literature search was conducted in 6 medical databases from inception to February 17, 2021 to identify studies evaluating colchicine as a therapeutic agent in COVID-19. All included studies were evaluated …

The Parkinson’S Prison And The Hero’S Journey To Escape: Improvisation And Storytelling In Parkinson’S Disease, Robert David Cochrane

UNLV Theses, Dissertations, Professional Papers, and Capstones

Parkinson’s disease (PD) is the fastest growing neurological disorder in the world, with leading researchers calling it a pandemic. While there is no cure, pharmaceuticals and surgical interventions increase people with Parkinson’s (PWP) ability to lead longer and more productive lives. However, there is a lack of care available for PWP supporting their social and emotional domains. PWP report high levels of stress, anxiety, and isolation due to the chronic and unpredictably progressive nature of the disease. This leads to a vicious cycle of loss of confidence, decreased activity and socialization, and increased falls.A common phrase in the PD community …

Anxiety, Depression, And Suicidal Ideation Among Transgender Individuals With Gender Receiving Gender-Affirming Hormone Therapy, Rosa E. Diaz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Purpose: Gender may align with one’s sex but doesn’t always and sometimes leads to Gender Dysphoria (GD). Gender-affirming hormone therapy (GAHT) is often one of the first medical treatments used for GD yet few studies have examined the effects of GAHT on mental health (depression, anxiety, and suicidal ideation).Methods: Participants were 18 years or older and self-reported as being diagnosed with GD and recruited across the United States using snowball and convenience sampling. The Patient Health Questionnaire-9 (PHQ-9) was used to measure depression scores, General Anxiety Disorder-7 (GAD-7) was used to measure anxiety scores, and Suicidal Behaviors Questionnaire-Revised (SBQ-R) was …

Covid-19 Isolation Compliance Among Students And Employees Of A Large Public University, Nicolette Harmon

UNLV Theses, Dissertations, Professional Papers, and Capstones

Isolation has been used to prevent the spread of many infectious diseases including COVID-19. The CDC’s isolation recommendations have changed over the course of the COVID-19 pandemic, currently infected individuals must stay at home for 5 full days. The CDC cites low compliance rates as one of the reasons for the recent reduction to the number of days in isolation. However, the CDC could only cite studies from other countries due to the lack of studies on isolation compliance in the United States. This study aimed to determine what percentage of UNLV students and staff complied with the isolation guidelines …

Self-Reported Covid-19 Diagnosis And Severity And Its Association With Utilization Of And Delays In Needed Medical Care, Mohammad Hesam Alavi

UNLV Theses, Dissertations, Professional Papers, and Capstones

Covid-19, caused by the virus SARS-CoV-2, was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. The pandemic-related disruptions and the pursuant lockdowns have adversely impacted every aspect of people’s lives including access to medical care, cancer care, preventive medicine, mental health, and dental care in an already imperfect healthcare system in the US. This study utilized the 2020 self-reported data from quarters 3 and 4 of the National Health Interview Survey, a cross-sectional interview survey by the Centers for Disease Control and Prevention, to determine the possible association of self-reported COVID diagnosis, test positivity, and …

Use Of Healthcare Utilization Records For Analyzing Trends In Clinical Toxoplasmosis: A Comparison Of Nevada And The United States, Elijah Kreutzer

UNLV Theses, Dissertations, Professional Papers, and Capstones

Toxoplasmosis, a zoonotic disease caused by the parasitic protist Toxoplasma gondii, is a ubiquitous, global public health concern with a wide variety of clinical manifestations. Surveillance for the disease is lacking even in developed countries, and what surveillance is present most often focuses on pregnant women. This research investigated trends in clinical toxoplasmosis in Nevada and nationally to address the lack of knowledge concerning how Nevada discharges compare to national discharges in cases of toxoplasmosis. Specifically, this research sought to determine what characterizes toxoplasmosis in Nevada across inpatient, outpatient, and emergency department settings, as well as how these cases differ …

Dimensionality Of Natural Auditory Scene Perception: A Factor Analysis Study, Margaret A. Mcmullin

UNLV Theses, Dissertations, Professional Papers, and Capstones

Theories of auditory and visual scene analysis suggest the perception of scenes relies on the identification and segregation of objects within it, resembling a detail-oriented processing style, but it is possible that a global-oriented process also occurs while evaluating auditory scenes. There is evidence for global properties that enable rapid recognition of visual scenes, even without recognizing the individual objects comprising the scene. It is our understanding that a similar line of research has not been explored in the auditory domain; therefore, we evaluated the contributions of high-level global and low-level acoustic information to auditory scene perception. A secondary aim …

Factors Associated With Immediate Postnatal Care In Lao People's Democratic Republic: An Analysis Of The 2017 Lao People's Democratic Republic Multiple Indicator Cluster Survey, Tressa Quayle

UNLV Theses, Dissertations, Professional Papers, and Capstones

Purpose: This study aimed to identify potential factors associated with immediate postnatal care in Laotian women. Background: The World Health Organization recognizes that approximately half of all maternal deaths occur in the immediate postnatal period or 24 hours after birth. One crucial step to improving maternal mortality is a postnatal check during the first 24 hours following birth. Forty-seven percent of Lao women aged 15-49 who delivered a baby in the last two years received a postnatal health check in the first two days after delivery. Of these, 46.5% of postnatal checks were conducted prior to discharge from the facility …

Metabolic Syndrome And Associated Factors Among Hispanic Americans, Shannon L. Richard

UNLV Theses, Dissertations, Professional Papers, and Capstones

Metabolic syndrome (MetS) is a cardiometabolic condition that may develop into cardiovascular disease and type 2 diabetes mellitus. Early recognition and associated treatment of MetS can help detour disease. Lifestyle factors, sleep-disordered breathing, and psychological well-being influence the development of MetS; electrocardiogram abnormalities are associated with MetS. Hispanics living in the United States are particularly vulnerable to MetS. Although MetS is well-identified in Americans of Hispanic ethnicity, the current literature evaluating protective and contributory factors among Hispanic gender-ethnic subgroups is inconsistent and incomplete. This study aimed to examine the relationships between MetS and select health and lifestyle factors among seven …

Effects Of Patellofemoral Pain On Central Activation And Function Of The Gluteus Medius Muscle In Physically Active Females, Michelle Samuel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Patellofemoral pain (PFP) is the most common knee injury among runners, military personnel, adolescents and recreationally active persons. PFP commonly presents as diffuse pain across the anterior knee that increases with activities such as running, squatting, and walking up and down stairs. Nearly 75% of patients with PFP either alter or completely stop physical activity as a result of the pain. There are numerous mechanisms that contribute to PFP symptoms; such as muscle weakness, abnormal joint mechanics and abnormal joint stress, which make it difficult to successfully treat. In addition, PFP may lead to patellofemoral joint (PFJ) osteoarthritis, a debilitating …

The Impact Of Alzheimer Disease On Semantic Knowledge, Maileen G. Ulep

UNLV Theses, Dissertations, Professional Papers, and Capstones

The research furthers the understanding of the impact of Alzheimer disease (AD) on cognition and the organization of semantic knowledge in the brain, which might contribute to the development of diagnostic and staging tools, and interventions to palliate cognitive deficits. The disruption of semantic knowledge in AD is well documented in the literature. Much of the existing research focuses on the general impact AD has on semantic knowledge. This study explores the impact of AD on specific domains of knowledge, chiefly, living kinds and artifacts, critical to ordinary functioning. The content, organization and structure of the investigated domains of knowledge …

Customer Willingness To Pay For All-Inclusive Resorts: A Choice-Based Conjoint Analysis, Liheng Zhang

UNLV Theses, Dissertations, Professional Papers, and Capstones

This dissertation examined customers’ willingness to pay for all-inclusive resorts using choice theory, the theory of bundling, and prospect theory. This dissertation also contributed to the current research by determining (a) the attributes that affect customers’ willingness to pay for an all-inclusive resort and (b) whether a reference price will affect customers’ willingness to pay. We also take into account the effect of the COVID-19 pandemic on customers and whether the pandemic will influence customers’ purchase behavior at this particular time. The choice-based conjoint analysis results showed that all eleven attributes—price, hotel star rating, type of room, location, food options, …

Histopathologic And Transcriptomic Phenotypes Of A Conditional Rankl Transgenic Mouse Thymus, Maria M Szwarc, Lan Hai, Vineet K Maurya, Kimal Rajapakshe, Dimuthu Perera, Michael M Ittmann, Qianxing Mo, Yong Lin, Matthew L Bettini, Cristian Coarfa, John P Lydon

Faculty, Staff and Students Publications

Although conventional knockout and transgenic mouse models have significantly advanced our understanding of Receptor Activator of NF-κB Ligand (RANKL) signaling in intra-thymic crosstalk that establishes self-tolerance and later stages of lymphopoiesis, the unique advantages of conditional mouse transgenesis have yet to be explored. A main advantage of conditional transgenesis is the ability to express a transgene in a spatiotemporal restricted manner, enabling the induction (or de-induction) of transgene expression during predetermined stages of embryogenesis or during defined postnatal developmental or physiological states, such as puberty, adulthood, and pregnancy. Here, we describe the K5: RANKL bigenic mouse, in which transgene derived …

Radial Collateral Ligament Injuries Of The Thumb Metacarpophalangeal Joint, Thomas W Mitchell, Scott A Mitchell, Chia Wu

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Injuries to the radial collateral ligament (RCL) of the thumb are thought to be relatively uncommon, especially when compared to the ulnar collateral ligament. However, the radial collateral ligament is increasingly recognized as critical for the overall stability of the thumb metacarpophalangeal joint. This article sets out to provide a comprehensive review of RCL injuries of the thumb MCP joint, including epidemiology, biomechanics, diagnosis, and treatment.

RECENT FINDINGS: Although traditionally thought to respond well to conservative management, especially when compared to injuries to the ulnar collateral ligament, there is mounting evidence that chronic RCL injury leads to …

Preclinical Behavioral Assessments Of Mitraginyne, The Main Psychoactive Alkaloid In Kratom, Rachel Burroughs

Dissertations

Mitragyna speciosa (kratom) is a medicinal plant indigenous to Southeast Asia and Africa with a long history of use for a variety of ailments, including diarrhea, pain relief, cough suppression, and amelioration of opiate withdrawal symptoms. Despite its status as an herbal remedy, kratom is banned in some countries due to a myriad of negative health risks. Preclinical psychopharmacology studies of mitragynine (MG), the main alkaloid of kratom, indicate it has opioid-like effects at higher doses and psychostimulant-like effects at lower doses. The current study utilized three rodent behavioral paradigms to evaluate the putative psychostimulant effects of MG. The specific …

Characterizing Treatment Resistance In Muscle Invasive Bladder Cancer Using The Chicken Egg Chorioallantoic Membrane Patient-Derived Xenograft Model, Hugo Villanueva, Gabrielle A Wells, Malachi T Miller, Mariana Villanueva, Ravi Pathak, Patricia Castro, Michael M Ittmann, Andrew G Sikora, Seth P Lerner

Faculty, Staff and Student Publications

BACKGROUND: Non-metastatic muscle invasive urothelial bladder cancer (MIBC) has a poor prognosis and standard of care (SOC) includes neoadjuvant cisplatin-based chemotherapy (NAC) combined with cystectomy. Patients receiving NAC have at best

METHODS: We optimized engraftment conditions for primary MIBC tumors using the CAM-PDX model and tested concordance between cisplatin-based chemotherapy response of patients to matching PDX tumors using tumor growth coupled with immunohistochemistry markers of proliferation and apoptosis. We also tested select kinase inhibitor response on chemotherapy-resistant bladder cancers on the CAM-PDX using tumor growth measurements and immuno-detection of proliferation marker, Ki-67.

RESULTS: Our results show primary, NAC-resistant, MIBC tumors …

A Framework For Detecting Noncoding Rare-Variant Associations Of Large-Scale Whole-Genome Sequencing Studies, Zilin Li, Xihao Li, Hufeng Zhou, Sheila M Gaynor, Margaret Sunitha Selvaraj, Theodore Arapoglou, Corbin Quick, Yaowu Liu, Han Chen, Ryan Sun, Rounak Dey, Donna K Arnett, Paul L Auer, Lawrence F Bielak, Joshua C Bis, Thomas W Blackwell, John Blangero, Eric Boerwinkle, Donald W Bowden, Jennifer A Brody, Brian E Cade, Matthew P Conomos, Adolfo Correa, L Adrienne Cupples, Joanne E Curran, Paul S De Vries, Ravindranath Duggirala, Nora Franceschini, Barry I Freedman, Harald H H Göring, Xiuqing Guo, Rita R Kalyani, Charles Kooperberg, Brian G Kral, Leslie A Lange, Bridget M Lin, Ani Manichaikul, Alisa K Manning, Lisa W Martin, Rasika A Mathias, James B Meigs, Braxton D Mitchell, May E Montasser, Alanna C Morrison, Take Naseri, Jeffrey R O'Connell, Nicholette D Palmer, Patricia A Peyser, Bruce M Psaty, Laura M Raffield, Susan Redline, Alexander P Reiner, Muagututi'a Sefuiva Reupena, Kenneth M Rice, Stephen S Rich, Jennifer A Smith, Kent D Taylor, Margaret A Taub, Ramachandran S Vasan, Daniel E Weeks, James G Wilson, Lisa R Yanek, Wei Zhao, Jerome I Rotter, Cristen J Willer, Pradeep Natarajan, Gina M Peloso, Xihong Lin

Faculty, Staff and Student Publications

Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limited ability in analyzing the noncoding genome. We propose a computationally efficient and robust noncoding RV association detection framework, STAARpipeline, to automatically annotate a whole-genome sequencing study and perform flexible noncoding RV association analysis, including gene-centric analysis and fixed window-based and dynamic window-based non-gene-centric analysis by incorporating variant functional annotations. In gene-centric analysis, STAARpipeline uses STAAR to group noncoding variants based on functional categories of genes and incorporate …