Medicine and Health Sciences Commons^™

Genetic Contributors Of Incident Stroke In 10,700 African Americans With Hypertension: A Meta-Analysis From The Genetics Of Hypertension Associated Treatments And Reasons For Geographic And Racial Differences In Stroke Studies, Nicole D. Armstrong, Vinodh Srinivasasainagendra, Amit Patki, Rikki M. Tanner, Bertha A. Hidalgo, Hemant K. Tiwari, Nita A. Limdi, Ethan M. Lange, Leslie A. Lange, Donna K. Arnett, Marguerite R. Irvin

Epidemiology and Environmental Health Faculty Publications

Background: African Americans (AAs) suffer a higher stroke burden due to hypertension. Identifying genetic contributors to stroke among AAs with hypertension is critical to understanding the genetic basis of the disease, as well as detecting at-risk individuals.

Methods: In a population comprising over 10,700 AAs treated for hypertension from the Genetics of Hypertension Associated Treatments (GenHAT) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) studies, we performed an inverse variance-weighted meta-analysis of incident stroke. Additionally, we tested the predictive accuracy of a polygenic risk score (PRS) derived from a European ancestral population in both GenHAT and REGARDS AAs …

A Cross-Sectional Survey Of Potential Factors, Motivations, And Barriers Influencing Research Participation And Retention Among People Who Use Drugs In The Rural Usa, Angela T. Hetrick, April M. Young, Miriam R. Elman, Sarann Bielavitz, Rhonda L. Alexander, Morgan Brown, Elizabeth Needham Waddell, P. Todd Korthuis, Kathryn E. Lancaster

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: Despite high morbidity and mortality among people who use drugs (PWUD) in rural America, most research is conducted within urban areas. Our objective was to describe influencing factors, motivations, and barriers to research participation and retention among rural PWUD.

METHODS: We recruited 255 eligible participants from community outreach and community-based, epidemiologic research cohorts from April to July 2019 to participate in a cross-sectional survey. Eligible participants reported opioid or injection drug use to get high within 30 days and resided in high-needs rural counties in Oregon, Kentucky, and Ohio. We aggregated response rankings to identify salient influences, motivations, and …

A 6-Cpg Validated Methylation Risk Score Model For Metabolic Syndrome: The Hypergen And Goldn Studies, Bertha A. Hidalgo, Bre Minniefield, Amit Patki, Rikki Tanner, Minoo Bagheri, Hemant K. Tiwari, Donna K. Arnett, Marguerite Ryan Irvin

Epidemiology and Environmental Health Faculty Publications

There has been great interest in genetic risk prediction using risk scores in recent years, however, the utility of scores developed in European populations and later applied to non-European populations has not been successful. The goal of this study was to create a methylation risk score (MRS) for metabolic syndrome (MetS), demonstrating the utility of MRS across race groups using cross-sectional data from the Hypertension Genetic Epidemiology Network (HyperGEN, N = 614 African Americans (AA)) and the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, N = 995 European Americans (EA)). To demonstrate this, we first selected cytosine-guanine dinucleotides …

Genomics Of Postprandial Lipidomics In The Genetics Of Lipid-Lowering Drugs And Diet Network Study, Marguerite R. Irvin, May E. Montasser, Tobias Kind, Sili Fan, Dinesh K. Barupal, Amit Patki, Rikki M. Tanner, Nicole D. Armstrong, Kathleen A. Ryan, Steven A. Claas, Jeffrey R. O’Connell, Hemant K. Tiwari, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled …

Framing Future Of Work Considerations Through Climate And Built Environment Assessment Of Volunteer Work Practices In The United States Equine Assisted Services, Kimberly I. Tumlin, Sa Liu, Jae-Hong Park

Epidemiology and Environmental Health Faculty Publications

The foundation of healthy workplace design is an understanding of work practices. Volunteers comprise the majority of the workforce in care centers using horses to address human health issues. Documentation is lacking on protections for worker well-being in equestrian microenvironments which are known to have the potential for dust exposures. Climate acts as a master variable in equestrian facility design and ventilation usage to address dust and temperature concerns. Using climate as an independent variable, our objective was to characterize space usage, safety, environmental control, and organizational practices through a national survey of equine assisted programs. We found that more …

Association Of Body Composition With Odds Of Breast Cancer By Molecular Subtype: Analysis Of The Mechanisms For Established And Novel Risk Factors For Breast Cancer In Nigerian Women (Mend) Study, Tomi Akinyemiju, Kelley Jones, Anjali Gupta, Taofik Oyekunle, Veeral Saraiya, April Deveaux, Omolola Salako, Allison Hall, Olusegun Alatise, Gabriel Ogun, Adewale Adeniyi, Omobolaji Ayandipo, Thomas Olajide, Olalekan Olasehinde, Olukayode Arowolo, Adewale Adisa, Oludolapo Afuwape, Aralola Olusanya, Aderemi Adegoke, Trygve O. Tollefsbol, Donna K. Arnett, H3 Africa Kidney Research Network, Adetola Daramola

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: The association between obesity and breast cancer (BC) has been extensively studied among US, European and Asian study populations, with often conflicting evidence. However, despite the increasing prevalence of obesity and associated conditions in Africa, the continent with the highest age-standardized BC mortality rate globally, few studies have evaluated this association, and none has examined in relation to molecular subtypes among African women. The current analysis examines the association between body composition, defined by body mass index (BMI), height, and weight, and BC by molecular subtype among African women.

METHODS: We estimated odds ratios (ORs) and 95% confidence intervals …

Association Of Manganese Biomarker Concentrations With Blood Pressure And Kidney Parameters Among Healthy Adolescents: Nhanes 2013–2018, Maria D. Politis, Jacob C. Freedman, Erin N. Haynes, Alison P. Sanders

Epidemiology and Environmental Health Faculty Publications

Deficiency or excess exposure to manganese (Mn), an essential mineral, may have potentially adverse health effects. The kidneys are a major organ of Mn site-specific toxicity because of their unique role in filtration, metabolism, and excretion of xenobiotics. We hypothesized that Mn concentrations were associated with poorer blood pressure (BP) and kidney parameters such as estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), and albumin creatinine ratio (ACR). We conducted a cross-sectional analysis of 1931 healthy U.S. adolescents aged 12–19 years participating in National Health and Nutrition Examination Survey cycles 2013–2014, 2015–2016, and 2017–2018. Blood and urine Mn concentrations …

Apobec Mutagenesis Is Concordant Between Tumor And Viral Genomes In Hpv-Positive Head And Neck Squamous Cell Carcinoma, Daniel L. Faden, Krystle A. Lang Kuhs, Maoxuan Lin, Adam Langenbucher, Maisa Pinheiro, Meredith Yeager, Michael Cullen, Joseph F. Boland, Mia Steinberg, Sara Bass, James S. Lewis, Michael S. Lawrence, Robert L. Ferris, Lisa Mirabello

Epidemiology and Environmental Health Faculty Publications

APOBEC is a mutagenic source in human papillomavirus (HPV)-mediated malignancies, including HPV+ oropharyngeal squamous cell carcinoma (HPV + OPSCC), and in HPV genomes. It is unknown why APOBEC mutations predominate in HPV + OPSCC, or if the APOBEC-induced mutations observed in both human cancers and HPV genomes are directly linked. We performed sequencing of host somatic exomes, transcriptomes, and HPV16 genomes from 79 HPV + OPSCC samples, quantifying APOBEC mutational burden and activity in both host and virus. APOBEC was the dominant mutational signature in somatic exomes. In viral genomes, there was a mean of five (range 0–29) mutations per …

Predictors Of Chronic Opioid Therapy In Medicaid Beneficiaries With Hiv Who Initiated Antiretroviral Therapy, Gyeon Oh, Emily S. Brouwer, Erin L. Abner, David W. Fardo, Patricia R. Freeman, Chris Delcher, Daniela C. Moga

Epidemiology and Environmental Health Faculty Publications

The factors associated with chronic opioid therapy (COT) in patients with HIV is understudied. Using Medicaid data (2002-2009), this retrospective cohort study examines COT in beneficiaries with HIV who initiated standard combination anti-retroviral therapy (cART). We used generalized estimating equations on logistic regression models with backward selection to identify significant predictors of COT initiation. COT was initiated among 1014 out of 9615 beneficiaries with HIV (male: 10.4%; female: 10.7%). Those with older age, any malignancy, Hepatitis C infection, back pain, arthritis, neuropathy pain, substance use disorder, polypharmacy, (use of) benzodiazepines, gabapentinoids, antidepressants, and prior opioid therapies were positively associated with …

Association Of Nonacute Opioid Use And Cardiovascular Diseases: A Scoping Review Of The Literature, Jade H. Singleton, Erin L. Abner, Peter D. Akpunonu, Anna M. Kucharska-Newton

Epidemiology and Environmental Health Faculty Publications

BACKGROUND

In this scoping review, we identified and reviewed 23 original articles from the PubMed database that investigated the relationship between nonacute opioid use (NOU) and cardiovascular outcomes.

METHODS AND RESULTS

We defined NOU to include both long-term opioid therapy and opioid use disorder. We summarized the association between NOU and 5 classes of cardiovascular disease, including infective endocarditis, coronary heart disease (including myocardial infarction), congestive heart failure, cardiac arrythmia (including cardiac arrest), and stroke. The most commonly studied outcomes were coronary heart disease and infective endocarditis. There was generally consistent evidence of a positive association between community prevalence of …

Identification Of Novel And Rare Variants Associated With Handgrip Strength Using Whole Genome Sequence Data From The Nhlbi Trans-Omics In Precision Medicine (Topmed) Program, Chloé Sarnowski, Han Chen, Mary L. Biggs, Sylvia Wassertheil-Smoller, Jan Bressler, Marguerite R. Irvin, Kathleen A. Ryan, David Karasik, Donna K. Arnett, L. Adrienne Cupples, David W. Fardo, Stephanie M. Gogarten, Benjamin D. Heavner, Deepti Jain, Hyun Min Kang, Charles Kooperberg, Arch G. Mainous, Braxton D. Mitchell, Alanna C. Morrison, Jeffrey R. O'Connell

Epidemiology and Environmental Health Faculty Publications

Handgrip strength is a widely used measure of muscle strength and a predictor of a range of morbidities including cardiovascular diseases and all-cause mortality. Previous genome-wide association studies of handgrip strength have focused on common variants primarily in persons of European descent. We aimed to identify rare and ancestry-specific genetic variants associated with handgrip strength by conducting whole-genome sequence association analyses using 13,552 participants from six studies representing diverse population groups from the Trans-Omics in Precision Medicine (TOPMed) Program. By leveraging multiple handgrip strength measures performed in study participants over time, we increased our effective sample size by 7-12%. Single-variant …

Factors That Influence Enrollment In Syringe Services Programs In Rural Areas: A Qualitative Study Among Program Clients In Appalachian Kentucky, Umedjon Ibragimov, Katherine E. Cooper, Evan Batty, April M. Ballard, Monica Fadanelli, Skylar B. Gross, Emma M. Klein, Scott Lockard, April M. Young, Hannah L. F. Cooper

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: Enrolling sufficient number of people who inject drugs (PWID) into syringe services programs (SSP) is important to curtail outbreaks of drug-related harms. Still, little is known about barriers and facilitators to SSP enrollment in rural areas with no history of such programs. This study's purpose was to develop a grounded theory of the role of the risk environment and individual characteristics of PWID in shaping SSP enrollment in rural Kentucky.

METHODS: We conducted one-on-one semi-structured interviews with 41 clients of 5 SSPs that were established in rural counties in Appalachian Kentucky in 2017-2018. Interviews covered PWID needs, the process …

Epigenome-Wide Association Study Of Kidney Function Identifies Trans-Ethnic And Ethnic-Specific Loci, Charles E. Breeze, Anna Batorsky, Mi Kyeong Lee, Mindy D. Szeto, Xiaoguang Xu, Daniel L. Mccartney, Rong Jiang, Amit Patki, Holly J. Kramer, James M. Eales, Laura Raffield, Leslie Lange, Ethan Lange, Peter Durda, Yongmei Liu, Russ P. Tracy, David Van Den Berg, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Mesa Multi-Omics Working Group, Kathryn L. Evans, William E. Kraus, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach.

METHODS: The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear …

Whole-Exome Sequencing And Hipsc Cardiomyocyte Models Identify Myrip, Trappc11, And Slc27a6 Of Potential Importance To Left Ventricular Hypertrophy In An African Ancestry Population, Marguerite R. Irvin, Praful Aggarwal, Steven A. Claas, Lisa De Las Fuentes, Anh N. Do, C. Charles Gu, Andrea Matter, Benjamin S. Olson, Amit Patki, Karen Schwander, Joshua D. Smith, Vinodh Srinivasasainagendra, Hemant K. Tiwari, Amy J. Turner, Deborah A. Nickerson, Dabeeru C. Rao, Ulrich Broeckel, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Indices of left ventricular (LV) structure and geometry represent useful intermediate phenotypes related to LV hypertrophy (LVH), a predictor of cardiovascular (CV) disease (CVD) outcomes.

Methods and Results: We conducted an exome-wide association study of LV mass (LVM) adjusted to height^2.7, LV internal diastolic dimension (LVIDD), and relative wall thickness (RWT) among 1,364 participants of African ancestry (AAs) in the Hypertension Genetic Epidemiology Network (HyperGEN). Both single-variant and gene-based sequence kernel association tests were performed to examine whether common and rare coding variants contribute to variation in echocardiographic traits in AAs. We then used a data-driven …

Sex, Diabetes Status And Cognition: Findings From The Study Of Longevity In Diabetes, Chris Moran, Paola Gilsanz, Michal S. Beeri, Rachel A. Whitmer, Mary E. Lacy

Epidemiology and Environmental Health Faculty Publications

INTRODUCTION: Women comprise two-thirds of people with dementia, making female sex a significant dementia risk factor. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are known dementia risk factors with an increasing global incidence. Understanding whether subtle sex differences persist in cognitive function prior to dementia in the context of diabetes may help elucidate the magnitude of sex effects on dementia risk.

RESEARCH DESIGN AND METHODS: We examined cross-sectional data from the Study of Longevity in Diabetes (SOLID), a prospective cohort study of members of Kaiser Permanente Northern California aged 60 years and older with T1D (n=758), T2D …

Estimating The Population Attributable Fraction Of Asthma Due To Electronic Cigarette Use And Other Risk Factors Using Kentucky Behavioral Risk Factor Survey Data, 2016-2017, W. Jay Christian, Courtney J. Walker

Epidemiology and Environmental Health Faculty Publications

Introduction: Electronic nicotine delivery systems ENDS have become popular in the United States among both new users of nicotine and those seeking less harmful alternatives to traditional cigarettes. Users often perceive ENDS as being less harmful than traditional cigarettes. This study investigated the relationship between use of ENDS and asthma in a representative sample of adults. Methods: For this cross-sectional study, we used data from the Kentucky Behavioral Risk Factor Surveillance System telephone survey data from 2016-2017. Using a weighted multivariable logistic regression analysis, we identified important covariates to adjust for to calculate the population attributable fraction (PAF) of asthma …