Medicine and Health Sciences Commons^™

Aims: Increasing Diversity In Graduate Medical Education Leadership, Lahia Yemane, Emma Omoruyi, Patricia Poitevien, Rebecca Blankenburg

Faculty, Staff and Student Publications

No abstract provided.

The Pendulum Of Fontan Fenestration, Nadia Hernandez, Sudipta Sen, Johanna Blair De Haan, Stephen Haskins, Amit Pawa

Faculty, Staff and Student Publications

No abstract provided.

Impact Of Covid19 On Maxillofacial Fractures In The Province Of L’Aquila, Abruzzo, Italy Review Of 296 Patients Treated With Statistical Comparison Of The Two-Year Pre-Covid19 And Covid19, Filippo Giovannetti, Ettore Lupi, Danilo Di Giorgio, Secondo Scarsella, Antonio Oliva, Desiderio Di Fabio, Paolo Prata, Giada Petricca, Valentino Valentini

Faculty, Staff and Student Publications

The aim of this study was to understand the impact of the COVID-19 pandemic on the epidemiology of maxillofacial trauma in a regional trauma center in L'Aquila, Abruzzo, Italy, during the first wave of the pandemic and comparted it to an equivalent period from 2015 to 2018. The authorshave retrospectively analyzed personal data, site of trauma, etiology, and mechanism of injury. Statistical analysis has been carried out utilizing IBM SPSS Statistics software (IBM Corp., Armonk, NY) and significance was accepted for P values of 0.05) as opposed to the etiology in which the road traffic accidents decreased in favor of …

Soy Diferente: A Qualitative Study On The Perceptions Of Recovery Following Traumatic Brain Injury Among Spanish-Speaking Us Immigrants, Monique R Pappadis, Angelle M Sander, Margaret A Struchen, Diana M Kurtz

Faculty, Staff and Students Publications

PURPOSE: To explore the impact of traumatic brain injury (TBI) on the quality of life (QoL) and self-concept of Spanish-speaking U.S. Hispanic immigrants with TBI.

MATERIALS AND METHODS: A prospective, qualitative study conducted in a county level I trauma center and community. Semi-structured interviews on QoL and self-concept following TBI were conducted with 24 Spanish-speaking U.S. Hispanic immigrants with TBI living in the community at least 6 months following injury.

RESULTS: Perceived facilitators of QoL included faith, hopefulness in recovery, empathy for others, and support from others. Perceived barriers to QoL mentioned were symptoms/consequences of injury, employment/financial changes, loss of …

Information Is Power: The Experiences, Attitudes And Needs Of Individuals Who Chose To Have Prenatal Genomic Sequencing For Fetal Anomalies, Catherine G Kernie, Julia Wynn, Allison Rosenbaum, Jessica De Voest, Stephanie Galloway, Jessica Giordano, Samantha Stover, Lauren Westerfield, Kelly Gilmore, Ronald J Wapner, Ignatia B Van Den Veyver, Neeta L Vora, Rebecca G Clifton, Aaron B Caughey, Wendy K Chung

Faculty, Staff and Students Publications

OBJECTIVE: This study sought to evaluate the experiences of individuals who chose to participate in a study and receive prenatal genomic sequencing (pGS) for fetuses with congenital structural anomalies.

METHOD: Individuals who received research results of prenatal sequencing were invited to participate in semi-structured interviews about their experiences. A constructivist grounded theory approach was used to code and analyze interviews.

RESULTS: Thirty-three participants from 27 pregnancies were interviewed. Participants were motivated to enroll in the study to find out more about their fetus' condition and prepare for the future. The waiting period was a time of significant anxiety for participants. …

Neurovascular Abnormalities In Retinopathy Of Prematurity And Emerging Therapies, Chang Dai, Jun Xiao, Chenguang Wang, Wei Li, Guanfang Su

Faculty, Staff and Students Publications

Blood vessels in the developing retina are formed in concert with neural growth, resulting in functional neurovascular network. Disruption of the neurovascular coordination contributes to the pathogenesis of retinopathy of prematurity (ROP), a potentially blinding retinal neovascular disease in preterm infants that currently lacks an approved drug therapy in the USA. Despite vasculopathy as predominant clinical manifestations, an increasing number of studies revealed complex neurovascular interplays among neurons, glial cells and blood vessels during ROP. Coordinated expression of glia-derived vascular endothelial growth factor (VEGF) in spatio-temporal gradients is pivotal to the formation of well-organized vascular plexuses in the healthy retina, …

Mucosal Immunology Of The Ocular Surface, Cintia S De Paiva, Anthony J St Leger, Rachel R Caspi

Faculty, Staff and Students Publications

The eye is a sensory organ exposed to the environment and protected by a mucosal tissue barrier. While it shares a number of features with other mucosal tissues, the ocular mucosal system, composed of the conjunctiva, Meibomian glands, and lacrimal glands, is specialized to address the unique needs of (a) lubrication and (b) host defense of the ocular surface. Not surprisingly, most challenges, physical and immunological, to the homeostasis of the eye fall into those two categories. Dry eye, a dysfunction of the lacrimal glands and/or Meibomian glands, which can both cause, or arise from, sensory defects, including those caused …

Persistent Opioid Use In Cataract Surgery Pain Management And The Role Of Nonopioid Alternatives, Richard S Davidson, Kendall Donaldson, Maggie Jeffries, Sumitra Khandelwal, Michael Raizman, Yasaira Rodriguez Torres, Terry Kim

Faculty, Staff and Students Publications

Cataracts are a leading cause of preventable blindness globally. Although care varies between developing and industrialized countries, surgery is the single effective approach to treating cataracts. From the earliest documented primitive cataract removals to today's advanced techniques, cataract surgery has evolved dramatically. As surgical techniques have developed, so have approaches to surgical pain management. With current cataract surgical procedures and advanced technology, anesthesia and intraoperative pain management have shifted to topical/intracameral anesthetics, with or without low-dose systemic analgesia and anxiolysis. Despite this, pain and discomfort persist in some patients and are underappreciated in modern cataract surgery. Although pain management has …

Age-Dependent White Matter Disruptions After Military Traumatic Brain Injury: Multivariate Analysis Results From Enigma Brain Injury, Heather C Bouchard, Paul M Thompson, Aristeidis Sotiras, Et Al.

2020-Current year OA Pubs

Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non-negative matrix factorization (NMF) is a data-driven approach that detects covarying patterns (components) within high-dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self-reported TBI history. NMF identified 12 independent components derived from fractional …

Phase I Trial Of Atm Inhibitor M3541 In Combination With Palliative Radiotherapy In Patients With Solid Tumors, Saiama N Waqar, Clifford Robinson, Anthony J Olszanski, Alexander Spira, Melissa Hackmaster, Luisa Lucas, Laura Sponton, Hulin Jin, Ursula Hering, Damien Cronier, Marianna Grinberg, Annick Seithel-Keuth, Ivan Diaz-Padilla, Jordan Berlin

2020-Current year OA Pubs

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase orchestrates DNA double strand break (DSB) repair; ATM inhibitors may therefore enhance the therapeutic effect of DSB-inducing treatments such as radiotherapy (RT). M3541 is an orally administered selective inhibitor of ATM.

METHODS: This phase I dose-escalation study evaluated the maximum-tolerated dose (MTD), recommended phase II dose(s) (RP2D), safety, pharmacokinetics (PK) and antitumor activity of M3541 in combination with fractionated palliative RT in patients with solid tumors. Fifteen patients received palliative RT (30 Gy in 10 fractions) and escalating doses of M3541 (50-300 mg administered on RT fraction days) guided by a Bayesian 2-parameter logistic …

Joint Eanm/Snmmi/Anzsnm Practice Guidelines/Procedure Standards On Recommended Use Of [18f]Fdg Pet/Ct Imaging During Immunomodulatory Treatments In Patients With Solid Tumors Version 1.0, E Lopci, R J Hicks, A Dimitrakopoulou-Strauss, L Dercle, A Iravani, R D Seban, C Sachpekidis, O Humbert, O Gheysens, A W J M Glaudemans, W Weber, R L Wahl, A M Scott, N Pandit-Taskar, N Aide

2020-Current year OA Pubs

PURPOSE: The goal of this guideline/procedure standard is to assist nuclear medicine physicians, other nuclear medicine professionals, oncologists or other medical specialists for recommended use of [

METHODS: In a cooperative effort between the EANM, the SNMMI and the ANZSNM, clinical indications, recommended imaging procedures and reporting standards have been agreed upon and summarized in this joint guideline/procedure standard.

CONCLUSIONS: The field of immuno-oncology is rapidly evolving, and this guideline/procedure standard should not be seen as definitive, but rather as a guidance document standardizing the use and interpretation of [

PREAMBLE: The European Association of Nuclear Medicine (EANM) is a …

Assessing Researchers' Capabilities, Opportunities, And Motivation To Conduct Equity-Oriented Dissemination And Implementation Research, An Exploratory Cross-Sectional Study, Ana A Baumann, Eva N Woodward, Rajinder Sonia Singh, Prajakta Adsul, Rachel C Shelton

2020-Current year OA Pubs

BACKGROUND: A recent paradigm shift has led to an explicit focus on enhancing health equity through equity-oriented dissemination and implementation (D&I) research. However, the integration and bidirectional learning across these two fields is still in its infancy and siloed. This exploratory study aimed to examine participants' perceived capabilities, opportunities, and motivations to conduct equity-oriented D&I research.

METHODS: We conducted an exploratory cross-sectional survey distributed online from December 2020 to April 2021. Participants were recruited at either D&I or health disparities-oriented conferences, meetings, through social media, or personal outreach via emails. Informed by the Capability, Opportunity, and Motivation Model (COM-B), the …

Association Of The Receptor For Activated C-Kinase 1 With Ribosomes In Plasmodium Falciparum, Jessey Erath, Sergej Djuranovic

2020-Current year OA Pubs

The receptor for activated C-kinase 1 (RACK1), a highly conserved eukaryotic protein, is known to have many varying biological roles and functions. Previous work has established RACK1 as a ribosomal protein, with defined regions important for ribosome binding in eukaryotic cells. In Plasmodium falciparum, RACK1 has been shown to be required for parasite growth, however, conflicting evidence has been presented about RACK1 ribosome binding and its role in mRNA translation. Given the importance of RACK1 as a regulatory component of mRNA translation and ribosome quality control, the case could be made in parasites that RACK1 either binds or does not …

Genomic And Transcriptomic Somatic Alterations Of Hepatocellular Carcinoma In Non-Cirrhotic Livers, Zachary L Skidmore, Jason Kunisaki, Yiing Lin, Kelsy C Cotto, Erica K Barnell, Jasreet Hundal, Kilannin Krysiak, Vincent Magrini, Lee Trani, Jason R Walker, Robert Fulton, Elizabeth M Brunt, Christopher A Miller, Richard K Wilson, Elaine R Mardis, Malachi Griffith, William Chapman, Obi L Griffith

2020-Current year OA Pubs

No abstract provided.

Protein Proximity Networks And Functional Evaluation Of The Casein Kinase 1 Gamma Family Reveal Unique Roles For Ck1Γ3 In Wnt Signaling, Megan J. Agajanian, Frances M. Potjewyd, Brittany M. Bowman, Smaranda Solomon, Kyle M. Lapak, Dhaval P. Bhatt, Jeffery L. Smith, Dennis Goldfarb, Alison D. Axtman, Michael B. Major

2020-Current year OA Pubs

Aberrant activation or suppression of WNT/β-catenin signaling contributes to cancer initiation and progression, neurodegeneration, and bone disease. However, despite great need and more than 40 years of research, targeted therapies for the WNT pathway have yet to be fully realized. Kinases are considered exceptionally druggable and occupy key nodes within the WNT signaling network, but several pathway-relevant kinases remain understudied and "dark." Here, we studied the function of the casein kinase 1γ (CSNK1γ) subfamily of human kinases and their roles in WNT signaling. miniTurbo-based proximity biotinylation and mass spectrometry analysis of CSNK1γ1, CSNK1γ2, and CSNK1γ3 revealed numerous components of the …

An Examination Of The Sex-Specific Nature Of Nutrition Assessment Within The Nutrition Care Process: Considerations For Nutrition And Dietetics Practitioners Working With Transgender And Gender Diverse Clients, Whitney Linsenmeyer, Sarah Garwood, Jennifer Waters

2020-Current year OA Pubs

No abstract provided.

Sustained Effect Of Lactin-V (Lactobacillus Crispatus Ctv-05) On Genital Immunology Following Standard Bacterial Vaginosis Treatment: Results From A Randomised, Placebo-Controlled Trial, Eric Armstrong, Anke Hemmerling, Steve Miller, Kerianne E. Burke, Sara J. Newmann, Sheldon R. Morris, Hilary Reno, Sanja Huibner, Maria Kulikova, Nico Nagelkerke, Bryan Coburn, Craig R. Cohen, Rupert Kaul

2020-Current year OA Pubs

BACKGROUND: Bacterial vaginosis might increase HIV risk by eliciting genital inflammation and epithelial barrier disruption, whereas vaginal Lactobacillus crispatus is associated with immune quiescence and HIV protection. We investigated the effect of a live biotherapeutic containing L crispatus CTV-05 (LACTIN-V) on genital immunology and key vaginal bacteria.

METHODS: This substudy included women aged 18-45 years who participated in the randomised, placebo-controlled, phase 2b trial of LACTIN-V to reduce bacterial vaginosis recurrence, conducted at four universities and hospitals in the USA. Women with negative results for sexually transmitted infection, pregnancy, and urinary tract infection were provided a 5-day course of vaginal …

Determination Of The Electronic Portal Imaging Device Pixel-Sensitivity-Map For Quality Assurance Applications. Part 2: Photon Beam Dependence, Michael Paul Barnes, Baozhou Sun, Brad Michael Oborn, Bishnu Lamichhane, Stuart Szwec, Matthew Schmidt, Bin Cai, Frederick Menk, Peter Greer

2020-Current year OA Pubs

PURPOSE: The EPID PSM is a useful EPID calibration method for QA applications. The dependence of the EPID PSM on the photon beam used to acquire it has been investigated in this study for the four available PSM methods. The aim is to inform upon the viability of applying a single PSM for all available photon beams to simplify PSM implementation and maintenance.

METHODS: Four methods of PSM determination were each measured once in a single session on a single TrueBeam ® STx linac using 6 MV, 10 MV, 6 MV Flattening-Filter-Free (FFF), and 10 MV FFF photon beams. The …

Determination Of The Electronic Portal Imaging Device Pixel-Sensitivity-Map For Quality Assurance Applications. Part 1: Comparison Of Methods, Michael Paul Barnes, Baozhou Sun, Brad Michael Oborn, Bishnu Lamichhane, Stuart Szwec, Matthew Schmidt, Bin Cai, Frederick Menk, Peter Greer

2020-Current year OA Pubs

PURPOSE: Calibration of a radiotherapy electronic portal imaging device (EPID) using the pixel-sensitivity-map (PSM) in place of the flood field correction improves the utility of the EPID for quality assurance applications. Multiple methods are available for determining the PSM and this study provides an evaluation to inform on which is superior.

METHODS: Three different empirical methods ("Calvary Mater Newcastle" [CMN], "Varian," and "WashU") and a Monte Carlo-based method of PSM determination were investigated on a single Varian TrueBeam STx linear accelerator (linac) with an aS1200 EPID panel. PSM measurements were performed for each empirical method three successive times using the …

Association Of State Medicaid Expansion Status With Rates Of Suicide Among Us Adults, Hetal Patel, Justin Barnes, Nosayaba Osazuwa-Peters, Laura Jean Bierut

2020-Current year OA Pubs

Importance: In the US, suicide is the 10th leading cause of death and a serious mental health emergency. National programs that address suicide list access to mental health care as key in prevention, and more large-scale policies are needed to improve access to mental health care and address this crisis. The Patient Protection and Affordable Care Act (ACA) Medicaid Expansion Program was implemented in several states with the goal of increasing access to the health care system.

Objective: To compare changes in suicide rates in states that expanded Medicaid under the ACA vs states that did not.

Design, Setting, and …

Risk For Post-Colonoscopy Irritable Bowel Syndrome In Patients With And Without Antibiotic Exposure: A Retrospective Cohort Study, Ravy K Vajravelu, Jordan M Shapiro, Josephine Ni, Shivani U Thanawala, James D Lewis, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Laboratory studies have demonstrated that antibiotic use in conjunction with bowel purgatives causes alterations to the gut microbiota. Because gut microbiota changes may be a trigger for the development of irritable bowel syndrome (IBS), we sought to assess whether individuals who undergo bowel cleansing for colonoscopy and have concurrent antibiotic exposure develop IBS at higher rates than individuals who undergo colonoscopy without antibiotic exposure.

METHODS: We used data from Optum's de-identified Clinformatics Data Mart Database in the United States to study a cohort of 50- to 55-year-olds who underwent screening colonoscopy. Individuals exposed to antibiotics within 14 …

Intracorporeal And Extracorporeal Anastomosis For Robotic-Assisted And Laparoscopic Right Colectomy: Short-Term Outcomes Of A Multi-Center Prospective Trial, Robert K Cleary, Matthew Silviera, Et Al.

2020-Current year OA Pubs

BACKGROUND: Studies to date show contrasting conclusions when comparing intracorporeal and extracorporeal anastomoses for minimally invasive right colectomy. Large multi-center prospective studies comparing perioperative outcomes between these two techniques are needed. The purpose of this study was to compare intracorporeal and extracorporeal anastomoses outcomes for robotic assisted and laparoscopic right colectomy.

METHODS: Multi-center, prospective, observational study of patients with malignant or benign disease scheduled for laparoscopic or robotic-assisted right colectomy. Outcomes included conversion rate, gastrointestinal recovery, and complication rates.

RESULTS: There were 280 patients: 156 in the robotic assisted and laparoscopic intracorporeal anastomosis (IA) group and 124 in the robotic …

Modelmatcher: A Scientist-Centric Online Platform To Facilitate Collaborations Between Stakeholders Of Rare And Undiagnosed Disease Research, J Michael Harnish, Lucian Li, Sanja Rogic, Guillaume Poirier-Morency, Seon-Young Kim, Kym M Boycott, Michael F Wangler, Hugo J Bellen, Philip Hieter, Paul Pavlidis, Zhandong Liu, Shinya Yamamoto

Duncan NRI Faculty and Staff Publications

Next-generation sequencing is a prevalent diagnostic tool for undiagnosed diseases and has played a significant role in rare disease gene discovery. While this technology resolves some cases, others are given a list of possibly damaging genetic variants necessitating functional studies. Productive collaborations between scientists, clinicians, and patients (affected individuals) can help resolve such medical mysteries, and provide insights into in vivo function of human genes. Furthermore, facilitating interactions between scientists and research funders, including non-profit organizations or commercial entities, can dramatically reduce the time to translate discoveries from bench to bedside. Several systems designed to connect clinicians and researchers with …

Parental Mosaicism For Apparent De Novo Genetic Variants: Scope, Detection, And Counseling Challenges, Roni Zemet, Ignatia B Van Den Veyver, Paweł Stankiewicz

Duncan NRI Faculty and Staff Publications

The disease burden of de novo mutations (DNMs) has been evidenced only recently when the common application of next-generation sequencing technologies enabled their reliable and affordable detection through family-based clinical exome or genome sequencing. Implementation of exome sequencing into prenatal diagnostics revealed that up to 63% of pathogenic or likely pathogenic variants associated with fetal structural anomalies are apparently de novo, primarily for autosomal dominant disorders. Apparent DNMs have been considered to primarily occur as germline or zygotic events, with consequently negligible recurrence risks. However, there is now evidence that a considerable proportion of them are in fact inherited from …

Aberrant Uterine Folding In Mice Disrupts Implantation Chamber Formation And Alignment Of Embryo-Uterine Axes, Manoj K Madhavan, Francesco J Demayo, John P Lydon, Niraj R Joshi, Asgerally T Fazleabas, Ripla Arora

Faculty, Staff and Students Publications

The uterine luminal epithelium folds characteristically in mammals, including humans, horses and rodents. Improper uterine folding in horses results in pregnancy failure, but the precise function of folds remains unknown. Here, we uncover dynamic changes in the 3D uterine folding pattern during early pregnancy with the entire lumen forming pre-implantation transverse folds along the mesometrial-antimesometrial axis. Using a time course, we show that transverse folds are formed before embryo spacing, whereas implantation chambers form as the embryo begins attachment. Thus, folds and chambers are two distinct structures. Transverse folds resolve to form a flat implantation region, after which an embryo …

Relationship Between Arterial Stiffness And Subsequent Cardiac Structure And Function In Young Adults With Youth-Onset Type 2 Diabetes: Results From The Today Study, Amy S Shah, Samuel S Gidding, Laure El Ghormli, Jeanie B Tryggestad, Kristen J Nadeau, Fida Bacha, Lorraine E Levitt Katz, Steven M Willi, Joao Lima, Elaine M Urbina

Faculty, Staff and Students Publications

BACKGROUND: Higher arterial stiffness may contribute to future alterations in left ventricular systolic and diastolic function. We tested this hypothesis in individuals with youth-onset type 2 diabetes from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.

METHODS: Arterial stiffness (pulse wave velocity [carotid-femoral, femoral-foot, and carotid-radial], augmentation index, brachial distensibility) was measured in 388 participants with type 2 diabetes (mean age, 21 years; diabetes duration, 7.7 ± 1.5 years). To reflect overall (composite) vascular stiffness, the five arterial stiffness measures were aggregated. An echocardiogram was performed in the same cohort 2 years later. Linear regression …

Prune1 C933g>A Synonymous Variant Induces Exon 7 Skipping, Disrupts The Dhha2 Domain, And Leads To An Atypical Nmihba Syndrome Presentation: Case Report And Review Of The Literature, Christina L Magyar, David R Murdock, Lindsay C Burrage, Hongzheng Dai, Seema R Lalani, Richard A Lewis, Yuezhen Lin, Marcela F Astudillo, Jill A Rosenfeld, Alyssa A Tran, James B Gibson, Undiagnosed Diseases Network, Carlos A Bacino, Brendan H Lee, Hsiao-Tuan Chao

Faculty, Staff and Students Publications

Prune exopolyphosphatase-1 (PRUNE1) encodes a member of the aspartic acid-histidine-histidine (DHH) phosphodiesterase superfamily that regulates cell migration and proliferation during brain development. In 2015, biallelic PRUNE1 loss-of-function variants were identified to cause the neurodevelopmental disorder with microcephaly, hypotonia, and variable brain abnormalities (NMIHBA, OMIM#617481). NMIHBA is characterized by the namesake features and structural brain anomalies including thinning of the corpus callosum, cerebral and cerebellar atrophy, and delayed myelination. To date, 47 individuals have been reported in the literature, but the phenotypic spectrum of PRUNE1-related disorders and their causative variants remains to be characterized fully. Here, we report a novel homozygous …

Radiopharmaceutical Quality Control Considerations For Accelerator-Produced Actinium Therapies, Diane S Abou, Patrick Zerkel, James Robben, Mark Mclaughlin, Tim Hazlehurst, David Morse, Thaddeus J Wadas, Darpan N Pandya, Reiko Oyama, Gregory Gaehle, Michael L Nickels, Daniel L J Thorek

2020-Current year OA Pubs

No abstract provided.

Joint Eanm, Snmmi And Iaea Enabling Guide: How To Set Up A Theranostics Centre, Ken Herrmann, Richard L Wahl, Et Al.

2020-Current year OA Pubs

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumours and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine. The roll-out of radioligand therapy for treating a high-incidence tumour such as prostate cancer requires the expansion of …

Gene-Lifestyle Interactions In The Genomics Of Human Complex Traits, Vincent Laville, Yun J Sung, Karen Schwander, Mary F Feitosa, Aldi T Kraja, Mike Province, C Charles Gu, D C Rao, Et Al

2020-Current year OA Pubs

The role and biological significance of gene-environment interactions in human traits and diseases remain poorly understood. To address these questions, the CHARGE Gene-Lifestyle Interactions Working Group conducted series of genome-wide interaction studies (GWIS) involving up to 610,475 individuals across four ancestries for three lipids and four blood pressure traits, while accounting for interaction effects with drinking and smoking exposures. Here we used GWIS summary statistics from these studies to decipher potential differences in genetic associations and G×E interactions across phenotype-exposure-ancestry combinations, and to derive insights on the potential mechanistic underlying G×E through in-silico functional analyses. Our analyses show first that …