Medicine and Health Sciences Commons^™

A Genome-Wide Association Study Discovers 46 Loci Of The Human Metabolome In The Hispanic Community Health Study/Study Of Latinos, Elena V Feofanova, Han Chen, Yulin Dai, Peilin Jia, Megan L Grove, Alanna C Morrison, Qibin Qi, Martha Daviglus, Jianwen Cai, Kari E North, Cathy C Laurie, Robert C Kaplan, Eric Boerwinkle, Bing Yu

Journal Articles

Variation in levels of the human metabolome reflect changes in homeostasis, providing a window into health and disease. The genetic impact on circulating metabolites in Hispanics, a population with high cardiometabolic disease burden, is largely unknown. We conducted genome-wide association analyses on 640 circulating metabolites in 3,926 Hispanic Community Health Study/Study of Latinos participants. The estimated heritability for 640 metabolites ranged between 0%-54% with a median at 2.5%. We discovered 46 variant-metabolite pairs (p value < 1.2 × 10

The Arabic Version Of The Personality Inventory For The Dsm-5 (Pid-5) In A Clinical Sample Of United Arab Emirates (Uae) Nationals, Olga Coelho, Rute Pires, Ana Sousa Ferreira, Bruno Gonçalves, Samia A. Alkhoori, Mohamed A. Sayed, Amany Elrasheed, Sara Belhoul, Maryam Aljassmi, Joana Stocker

All Works

Objectives: We aimed to test the potential of the Arabic version of the PID-5 to distinguish between clinical and non-clinical participants, as well as to examine its convergent validity and factor structure in an Emirati clinical sample. Methods: The Arabic version of the PID-5 was administered to a clinical sample comprised of 156 participants (Mage = 31.38, SD = 8.99, 37.8% male, 62.2% female) and a community sample also comprised of 156 participants (Mage = 31.43, SD = 9.52, 37.2% male, 62.8% female). We addressed the descriptive measures, internal consistency, mean rank scores differences, convergent validity with SCL-90-R, and PID-5's …

Representation Of Ehr Data For Predictive Modeling: A Comparison Between Umls And Other Terminologies., Laila Rasmy, Firat Tiryaki, Yujia Zhou, Yang Xiang, Cui Tao, Hua Xu, Degui Zhi

Journal Articles

OBJECTIVE: Predictive disease modeling using electronic health record data is a growing field. Although clinical data in their raw form can be used directly for predictive modeling, it is a common practice to map data to standard terminologies to facilitate data aggregation and reuse. There is, however, a lack of systematic investigation of how different representations could affect the performance of predictive models, especially in the context of machine learning and deep learning.

MATERIALS AND METHODS: We projected the input diagnoses data in the Cerner HealthFacts database to Unified Medical Language System (UMLS) and 5 other terminologies, including CCS, CCSR, …

Genetic Variant Effects On Gene Expression In Human Pancreatic Islets And Their Implications For T2d., Ana Viñuela, Arushi Varshney, Martijn Van De Bunt, Rashmi B Prasad, Olof Asplund, Amanda Bennett, Michael Boehnke, Andrew A Brown, Michael R Erdos, João Fadista, Ola Hansson, Gad Hatem, Cédric Howald, Apoorva K Iyengar, Paul Johnson, Ulrika Krus, Patrick E Macdonald, Anubha Mahajan, Jocelyn E Manning Fox, Narisu Narisu, Vibe Nylander, Peter Orchard, Nikolay Oskolkov, Nikolaos I Panousis, Anthony Payne, Michael L. Stitzel, Swarooparani Vadlamudi, Ryan Welch, Francis S Collins, Karen L Mohlke, Anna L Gloyn, Laura J Scott, Emmanouil T Dermitzakis, Leif Groop, Stephen C J Parker, Mark I Mccarthy

Faculty Research 2020

Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. We find: (a) 7741 cis-eQTLs in islets with a replication rate across 44 GTEx tissues between 40% and 73%; (b) marked overlap between islet cis-eQTL signals and active regulatory sequences in islets, with reduced eQTL effect size observed in …

Prognostic Gene Expression Signature For High-Grade Serous Ovarian Cancer., J Millstein, T Budden, E L Goode, M S Anglesio, A Talhouk, M P Intermaggio, H S Leong, S Chen, W Elatre, B Gilks, T Nazeran, M Volchek, R C Bentley, C Wang, D S Chiu, S Kommoss, S C Y Leung, J Senz, A Lum, V Chow, H Sudderuddin, R Mackenzie, Joshy George, Aocs Group, S Fereday, J Hendley, N Traficante, H Steed, J M Koziak, M Köbel, I A Mcneish, T Goranova, D Ennis, G Macintyre, D Silva De Silva, T Ramón Y Cajal, J García-Donas, S Hernando Polo, G C Rodriguez, K L Cushing-Haugen, H R Harris, C S Greene, R A Zelaya, S Behrens, R T Fortner, P Sinn, E Herpel, J Lester, J Lubiński, O Oszurek, A Tołoczko, C Cybulski, J Menkiszak, C L Pearce, M C Pike, C Tseng, J Alsop, V Rhenius, H Song, M Jimenez-Linan, A M Piskorz, A Gentry-Maharaj, C Karpinskyj, M Widschwendter, N Singh, C J Kennedy, R Sharma, P R Harnett, B Gao, S E Johnatty, R Sayer, J Boros, S J Winham, G L Keeney, S H Kaufmann, M C Larson, H Luk, B Y Hernandez, P J Thompson, L R Wilkens, M E Carney, B Trabert, J Lissowska, L Brinton, M E Sherman, C Bodelon, S Hinsley, L A Lewsley, R Glasspool, S N Banerjee, E A Stronach, P Haluska, I Ray-Coquard, S Mahner, B Winterhoff, D Slamon, D A Levine, L E Kelemen, J Benitez, J Chang-Claude, J Gronwald, A H Wu, U Menon, M T Goodman, J M Schildkraut, N Wentzensen, R Brown, A Berchuck, G Chenevix-Trench, A Defazio, S A Gayther, M J García, M J Henderson, M A Rossing, A Beeghly-Fadiel, P A Fasching, S Orsulic, B Y Karlan, G E Konecny, D G Huntsman, D D Bowtell, J D Brenton, J A Doherty, P D P Pharoah, S J Ramus

Faculty Research 2020

BACKGROUND: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC.

PATIENTS AND METHODS: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for …

Dual Roles Of Neutrophils In Metastatic Colonization Are Governed By The Host Nk Cell Status., Peishan Li, Mingyang Lu, Jiayuan Shi, Li Hua, Zheng Gong, Qing Li, Leonard D. Shultz, Guangwen Ren

Faculty Research 2020

The role of neutrophils in solid tumor metastasis remains largely controversial. In preclinical models of solid tumors, both pro-metastatic and anti-metastatic effects of neutrophils have been reported. In this study, using mouse models of breast cancer, we demonstrate that the metastasis-modulating effects of neutrophils are dictated by the status of host natural killer (NK) cells. In NK cell-deficient mice, granulocyte colony-stimulating factor-expanded neutrophils show an inhibitory effect on the metastatic colonization of breast tumor cells in the lung. In contrast, in NK cell-competent mice, neutrophils facilitate metastatic colonization in the same tumor models. In an ex vivo neutrophil-NK cell-tumor cell …

Aluminum Reproductive Toxicity: A Summary And Interpretation Of Scientific Reports, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Publications addressing aluminum (Al)-induced reproductive toxicity were reviewed. Key details were compiled in summary tables. Approximate systemic Al exposure, a measure of bioavailability, was calculated for each exposure, based on the Al percentage in the dosed Al species, Al bioavailability, and absorption time course reports for the exposure route. This was limited to laboratory animal studies because no controlled-exposure human studies were found. Intended Al exposure was compared to unintended dietary Al exposure. The considerable and variable Al content of laboratory animal diets creates uncertainty about reproductive function in the absence of Al. Aluminum-induced reproductive toxicity in female mice and …

Facial Shape And Allometry Quantitative Trait Locus Intervals In The Diversity Outbred Mouse Are Enriched For Known Skeletal And Facial Development Genes., David C Katz, J David Aponte, Wei Liu, Rebecca M Green, Jessica M Mayeux, K Michael Pollard, Daniel Pomp, Steven C. Munger, Stephen A Murray, Charles C Roseman, Christopher J Percival, James Cheverud, Ralph S Marcucio, Benedikt Hallgrímsson

Faculty Research 2020

The biology of how faces are built and come to differ from one another is complex. Discovering normal variants that contribute to differences in facial morphology is one key to untangling this complexity, with important implications for medicine and evolutionary biology. This study maps quantitative trait loci (QTL) for skeletal facial shape using Diversity Outbred (DO) mice. The DO is a randomly outcrossed population with high heterozygosity that captures the allelic diversity of eight inbred mouse lines from three subspecies. The study uses a sample of 1147 DO animals (the largest sample yet employed for a shape QTL study in …

Evidence For Gene-Smoking Interactions For Hearing Loss And Deafness In Japanese American Families, Jia Y Wan, Christina Cataby, Andrew Liem, Emily Jeffrey, Trina M Norden-Krichmar, Deborah Goodman, Stephanie A Santorico, Karen L Edwards

Journal Articles

BACKGROUND: This study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identified genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with …

Digilego For Peripartum Depression: A Novel Patient-Facing Digital Health Instantiation, J Rodin, C Timko, S Harris

Journal Articles

Digital health technologies offer unique opportunities to improve health outcomes for mental health conditions such as peripartum depression (PPD), a disorder that affects approximately 10-15% of women in the U.S. every year. In this paper, we present the adaption of a digital technology development framework, Digilego, in the context of PPD. Methods include mapping of the Behavior Intervention Technology (BIT) model and the Patient Engagement Framework (PEF) to translate patient needs captured through focus groups. This informs formative development and implementation of digital health features for optimal patient engagement in PPD screening and management. Results show an array ofPPD-specific Digilego …

Kinematic And Coordination Variability In Runners With And Without Patellofemoral Pain, Jessica Mutchler, Klarie Macias, Barry Munkasy, Samuel J. Wilson, John C. Garner Iii, Li Li

Department of Health Sciences and Kinesiology Faculty Publications

Background: Patellofemoral pain (PFP) is a common overuse injury that has been suggested to cause abnormal gait kinematics and variability in runners with PFP. Conflicting results have been presented as to the variability of joint kinematics and joint coordination. Objective: The purpose of this study was to examine the variability of lower extremity kinematics and joint coordination in the presence of PFP and exertion. Methods: Six female runners with PFP and matched controls (CON) ran at a self-selected pace on an instrumented treadmill until exertion or pain criteria was met. Sixteen anatomical retroreflective markers and seven tracking clusters were placed …

Effects Of A Strength Training Intervention And Quality Of Life: Case Study On A Sedentary Adult Female, Lucas Frazier

Williams Honors College, Honors Research Projects

The purpose of the project is to evaluate physiological and quality of life changes in a

sedentary, senior-aged (55 or older) female using a six-week strength training

intervention. This case study will instruct how to perform a push-pull-legs split

routine by going to the gym three times per week. Prior to the six week intervention,

both quantitative and qualitative variables will be collected to assess baseline data,

including the subject’s resting heart rate, resting blood pressure, grip strength, one-

repetition maximum on seven whole body exercises (dumbbell bicep curl, tricep

pushdown, barbell bench press, wide-grip lat pull-down, seated dumbbell press, …