Public Health Commons^™

Cellstaar: Incorporating Single-Cell-Sequencing-Based Functional Data To Boost Power In Rare Variant Association Testing Of Noncoding Regions, Eric Van Buren, Yi Zhang, Xihao Li, Margaret Sunitha Selvaraj, Zilin Li, Hufeng Zhou, Nicholette D Palmer, Donna K Arnett, John Blangero, Eric Boerwinkle, Brian E Cade, Jenna C Carlson, April P Carson, Yii-Der Ida Chen, Joanne Curran, Ravindranath Duggirala, Myriam Fornage, Nora Franceschini, Misa Graff, Charles Gu, Xiuqing Guo, Jiang He, Nancy Heard-Cosa, Lifang Hou, Yi-Jen Hung, Rita R Kalyani, Sharon L R Kardia, Eimear Kenny, Charles Kooperberg, Brian G Kral, Leslie Lange, Dan Levy, Changwei Li, Simin Liu, Donald Lloyd-Jones, Ruth J F Loos, Ani W Manichaikul, Lisa Warsinger Martin, Rasika Mathias, Ryan L Minster, Braxton D Mitchell, Josyf C Mychaleckyj, Take Naseri, Kari North, Jeff O'Connell, James A Perry, Patricia A Peyser, Bruce M Psaty, Laura M Raffield, Ramachandran S Vasan, Susan Redline, Alex P Reiner, Stephen S Rich, Jennifer A Smith, Brian Spitzer, Hua Tang, Kent D Taylor, Russell Tracy, Satupa'itea Viali, Lisa Yanek, Wei Zhao, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Jerome I Rotter, Gina M Peloso, Pradeep Natarajan, Xihong Lin

Faculty, Staff and Student Publications

Understanding how rare genetic variants influence complex traits remains a major challenge, particularly when these variants lie in noncoding regions of the genome. The effects of variants within candidate cis-regulatory elements (cCREs) often depend on the cell type, making interpretation difficult. Here we introduce cellSTAAR, which integrates whole-genome sequencing data with single-cell assay for transposase-accessible chromatin using sequencing data to capture variability in chromatin accessibility across cell types via the construction of cell-type-specific functional annotations and regulatory elements. To reflect the uncertainty in cCRE-gene linking, cellSTAAR uses a comprehensive strategy to link cCREs to their target genes. We applied cellSTAAR …

Multilevel Analysis Of The Food And Physical Activity Environment And Adult Obesity Across U.S. Counties And States, Ann Mary Abraham, Michael D Swartz, Alexandra E Van Den Berg, Stephen H Linder

Faculty, Staff and Student Publications

Adult obesity rates have risen steadily across the United States over the past decade, with more than 40% of adults affected. Persistent geographic and demographic disparities exist in obesity prevalence across the nation. While prior research has examined individual or environmental associated factors of obesity, limited studies have addressed both physical activity and food environments across the nation using multilevel approaches. This cross-sectional ecological study (2014-2024) used a two-level random intercept model to assess the association between county- and state-level factors and adult obesity prevalence across over 3000 U.S. counties nested within 51 states. County-level associated factors included food insecurity, …

Cross-Ancestry Comparison Of Aptamer And Antibody Protein Measures, Jayna C Nicholas, Daniel H Katz, Usman A Tahir, Catherine L Debban, Francois Aguet, Thomas Blackwell, Russell P Bowler, K Alaine Broadaway, Jingsha Chen, Clary B Clish, Josef Coresh, Elaine Cornell, Daniel E Cruz, Rajat Deo, Margaret F Doyle, Peter Durda, Lynette Ekunwe, James S Floyd, Dipender Gill, Xiuqing Guo, Ron C Hoogeveen, Craig Johnson, Leslie A Lange, Yun Li, Alisa Manning, James B Meigs, Michael Y Mi, Josyf C Mychaleckyj, Nels C Olson, Katherine A Pratte, Brucy M Psaty, Alexander P Reiner, Peifeng Ruan, Magdalena Sevilla-Gonzalez, Amil M Shah, Quan Sun, Russell P Tracy, Jia Wen, Alexis C Wood, James G Wilson, Kristin L Young, Bing Yu, Mary R Rooney, Ani Manichaikul, Ruth Dubin, Karen L Mohlke, Stephen S Rich, Jerome I Rotter, Peter Ganz, Robert E Gerszten, Kent D Taylor, Laura M Raffield

Faculty, Staff and Student Publications

Measures from affinity-proteomics platforms often correlate poorly, challenging interpretation of protein associations with genetic variants and phenotypes. Here, we examine 2157 proteins measured on both SomaScan 7k and Olink Explore 3072 across 1930 participants with genetic similarity to European, African, East Asian, and Admixed American ancestry references. Inter-platform correlation coefficients for these 2157 proteins follow a bimodal distribution (median r = 0.30). We evaluate protein measure associations with genetic variants, and find approximately 25-30% of the signals on each platform are likely driven by protein-altering variants. We highlight 80 proteins that correlate differently across ancestry groups likely in part due …

Metabolome Contribution To Sex Differences In The Link Between Alcohol Consumption And Type 2 Diabetes: A Prospective Analysis In The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Brian Wang, Kai Luo, Wenyan Ma, Yanbo Zhang, Christina Cordero, Amber Pirzada, Martha Daviglus, Krista M Perreira, Bing Yu, Eric Boerwinkle, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

Background: Light-to-moderate alcohol consumption has been linked to improved insulin resistance and lower type 2 diabetes (T2D) risk predominantly in females but not males. Potential mechanisms underlying this sex difference remain unclear.

Objective: This study evaluated associations of sex-specific alcohol-associated metabolomic signatures (AMSs) with insulin resistance and T2D risk in US Hispanic/Latino adults.

Methods: We analyzed serum metabolome data in the HCHS/SOL, a prospective, multicenter, community-based study of Hispanics/Latinos, aged 18 to 74 years old, enrolled from four U.S. metropolitan areas between 2008 and 2011. Sex-specific AMSs were developed using Elastic Net to identify serum metabolites uniquely associated with alcohol …

Long-Term Mpox Sequelae 11 To 18 Months After Acute Illness : A Cohort Study In Two Us Cities, Preetam A Cholli, Jason Zucker, Karen J Vigil, Faisal S Minhaj, Paul J Weidle, Melanie M Taylor, Brett Gray, Dana L Haberling, Agha Ajmal, Agam K Rao, Anyelina Cantos, Sarah Anne J Guagliardo, Max Flanagan, Gilhen H Rodriguez, Irene Tamí-Maury, Siobhán M O'Connor

Faculty, Staff and Student Publications

Background: Little was known about persistent sequelae of mpox before the 2022 multinational clade II mpox virus outbreak.

Objective: To characterize post-mpox sequelae 11 to 18 months after acute mpox diagnosis and compare outbreak-associated psychosocial and behavioral impact between at-risk persons who had or did not have mpox.

Design: Cohort study.

Setting: New York City, New York, and Houston, Texas.

Participants: Adults attending HIV, pre-exposure prophylaxis, or sexually transmitted infection clinics diagnosed with mpox during May 2022 to January 2023 (post-mpox) or at risk for but never diagnosed with mpox (no-mpox).

Measurements: All participants completed psychosocial and behavioral self-assessments. A …

Pesticides Associated With Incident Diabetes Among Licensed Private Pesticide Applicators In The Agricultural Health Study Cohort (1993–2021), Christine G Parks, Qian Xiao, Jesse Wilkerson, Jonathan N Hofmann, Laura E Beane Freeman, Dale P Sandler

Faculty, Staff and Student Publications

Background: Growing evidence suggests pesticides may increase risk of type 2 diabetes, but data are limited on many specific chemicals.

Methods: In 29,527 private pesticide applicators in the Agricultural Health Study cohort (enrolled 1993-1997 in Iowa and North Carolina), 3,847 incident diabetes cases were identified by self-report during follow-up surveys in 1999-2003, 2005-2010, 2013-2015, and 2019-2021. We examined 50 pesticides reported at enrollment, updated in 1999-2003 or 2005-2010, prior to diabetes diagnosis or end of follow-up, using log-binomial regression to calculate relative risks (RR) and 95% confidence intervals (CI) for ever-use and intensity-weighted lifetime days (IWLD) use (tertiles, T1-3), adjusting …

Reducing Work-Related Screen-Time In Healthcare Workers During Leisure Time (Reduce Screen) - A Randomized Controlled Trial, Karsten Bartels, Karan Shah, Emelind Sanchez Rodriguez, Julie T Hoffman, Megan L Rolfzen, Juana Mora Valdovinos, Afton L Hassett, Daniel I Sessler

Faculty, Staff and Student Publications

The ubiquitous availability of work-related applications on personal devices makes healthcare workers prone to working during leisure time. We tested the hypothesis that an intervention to reduce work-related screen time during a weekend off reduces stress in healthcare workers in a pragmatic parallel design randomized controlled trial between November 2021 and November 2023. Healthcare workers using a smartphone with a work email application were eligible. Randomization was 1:1 to no treatment or a threefold educational intervention to: 1) activate automated responses to emails received, 2) reduce screen time, and 3) uninstall work applications from personal devices. The primary outcome was …

Whole Genome Sequence Analysis Of Pulmonary Function And Copd In 44,287 Multi-Ancestry Participants, Wonji Kim, Xiaowei Hu, Kangjin Kim, Sung Chun, Peter Orchard, Dandi Qiao, Ingo Ruczinski, Aabida Saferali, Francois Aguet, Lucinda Antonacci-Fulton, Pallavi P Balte, Traci M Bartz, Wardatul Jannat Anamika, Xiaobo Zhou, Junyi Duan, Jennifer A Brody, Brian E Cade, Martha L Daviglus, Harshavadran Doddapaneni, Shannon Dugan-Perez, Susan K Dutcher, Christian D Frazar, Stacey B Gabriel, Sina A Gharib, Namrata Gupta, Brian D Hobbs, Silva Kasela, Laura R Loehr, Ginger A Metcalf, Donna M Muzny, Elizabeth C Oelsner, Laura J Rasmussen-Torvik, Colleen M Sitlani, Joshua Smith, Tamar Sofer, Hanfei Xu, Bing Yu, David Zhang, John Ziniti, R Graham Barr, April P Carson, Myriam Fornage, Lifang Hou, Ravi Kalhan, Robert Kaplan, Tuuli Lappalainen, Stephanie J London, Alanna C Morrison, George T O'Connor, Bruce M Psaty, Laura M Raffield, Susan Redline, Stephen S Rich, Jerome I Rotter, Edwin K Silverman, Ani Manichaikul, Michael H Cho

Faculty, Staff and Student Publications

Background: Whole genome sequence (WGS) data in multi-ancestry samples supports discovery of low-frequency or population-specific genetic variants associated with chronic obstructive pulmonary disease (COPD) and lung function.

Results: We performed single variant, structural variant, and gene-based analysis of pulmonary function (FEV1, FVC and FEV1/FVC) and COPD case-control status in 44,287 multi-ancestry participants from the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We validated findings using the UK Biobank and assessed implicated genes using lung single-cell RNA-seq (scRNA-seq) data sets. Applying a genome-wide significance threshold (P < 5 × 10-9), we replicated known loci and identified novel associations near LY86, MAGI1, GRK7, and LINC02668. Colocalization with gene expression quantitative trait loci (eQTL) from the Lung Tissue Research Consortium highlighted known candidate genes including ADAM19, THSD4, C4B, and PSMA4, which were not identified through other eQTL sources. Multi-ancestry analysis improved fine-mapping resolution (e.g., HTR4 and RIN3). Gene-based analysis identified and replicated HMCN1. In human lung scRNA-seq data sets, lung epithelial cells and immune cell types showed enriched expression, while fibroblasts showed higher expression for HMCN1. CRISPR targeting HMCN1 in IMR90 demonstrated reduced expression of collagen genes.

Conclusions: Large-scale multi-ancestry WGS analysis improves variant discovery and fine-mapping resolution for lung function and …

Rab5c Increases Endothelial Release Of Vwf By Regulating Vesicle Trafficking, Paula Reventun, Pablo Toledano-Sanz, Maria Delgado-Marin, Maria Viskadourou, D Brian Foster, Paul S De Vries, Maria Sabater-Lleal, Nunzio Alcharani, Claudia Gonzalez-Cucharero, William O Osburn, Alanna C Morrison, Alisa S Wolberg, Nicholas L Smith, Marios Arvanitis, Charles J Lowenstein

Faculty, Staff and Student Publications

Background: Abnormal levels of VWF (von Willebrand Factor) are a risk factor for venous thromboembolism (VTE) and bleeding. Genome-wide association studies for VWF have identified novel candidate genes that may regulate VWF levels in humans, including RAB5C (RAS-associated protein RAB5C). We hypothesized that RAB5C regulates VWF release from endothelial cells.

Methods: We studied the effect of RAB5C on vesicle trafficking in human endothelial cells. We performed CRISPR (clustered regularly interspaced short palindromic repeats) interference targeting 2 genetic variants linked to altered VWF levels and evaluated RAB5C expression by reverse transcription-quantitative polymerase chain reaction. We silenced RAB5C or overexpressed RAB5C wild-type, …

Genomics Reveal Staphylococcus Aureus Persists During Long-Term Urinary Catheterization Despite Antimicrobial Therapy And Catheter Exchanges, Jesus M Duran Ramirez, Chelsie E Armbruster, Blake M Hanson, Jennifer N Walker

Faculty, Staff and Student Publications

Urinary catheters, the most frequently placed medical devices in the US, increase the risk of developing symptomatic catheter-associated urinary tract infection (CAUTI) and asymptomatic bacteriuria (ASB) - the presence of bacteria in the urine - with those requiring long-term urinary catheters (LTUCs) at highest risk. While ASB and CAUTI are caused by a broad range of uropathogens, most remain understudied. We use whole-genome sequencing to investigate the understudied uropathogen, Staphylococcus aureus. Analysis of 153 longitudinal S. aureus isolates previously collected from urinary catheter or urine samples from 20 individuals with LTUCs (average of 8 longitudinal isolates/person) demonstrates that most strains …

A Novel Vision Transformer Model Produces Clock Drawing Test Scores As Accurate As Expert Human Coders, Mengyao Hu, Tian Qin, Richard Gonzalez, Vicki A Freedman, Laura B Zahodne, Edmundo R Melipillán, Yi Lu Murphey

Faculty, Staff and Student Publications

Alzheimer's disease and related dementias is a growing public health concern. The clock-drawing test, where subjects draw a clock, typically with hands showing 11:10, has been widely used for dementia screening. A limitation of including the clock-drawing test in large-scale studies is that it requires manual coding, which could result in biases if coders interpret and implement coding rules differently. This study created and evaluated an intelligent Clock Scoring system built with deep learning neural networks to automatically code clock-drawing images. We used a large, publicly available repository of clock-drawing images from the 2011-2019 National Health and Aging Trends Study …

Self-Efficacy Change Among Diverse Family Caregivers In Dementia Care, Deborah M Oyeyemi, Erich J Greene, Yunshan Xu, David R Lee, Rafael Samper-Ternent, Maya L Lichtenstein, Alan Stevens, Jeff D Williamson, Arun S Karlamangla, Debra Saliba, David B Reuben

Faculty, Staff and Student Publications

Objectives: To determine whether changes in caregiver self-efficacy (beliefs about one's ability to manage dementia-related problems and access help) differed by caregiver race and ethnicity across all participants enrolled in a large pragmatic trial of comprehensive dementia care.

Methods: In the Dementia Care Study (D-CARE), community-dwelling older adults with dementia and their unpaid family caregivers were randomized to receive usual care, community-based, or health system-based comprehensive dementia care. Caregiver self-efficacy was assessed at baseline, 6 months, and 18 months using a 4-item scale (range 4-20, higher scores indicate greater self-efficacy). Among all caregivers, we compared least squares means for overall …

Large-Scale Blood Pressure Gwas Accounting For Gene-Depression Interactions In 564,680 Individuals From Diverse Populations, Songmi Lee, Clint L Miller, Amy R Bentley, Michael R Brown, Pavithra Nagarajan, Raymond Noordam, John L Morrison, Karen Schwander, Kenneth Westerman, Minjung Kho, Aldi T Kraja, Paul S De Vries, Farah Ammous, Hughes Aschard, Traci M Bartz, Anh Do, Charles T Dupont, Mary F Feitosa, Valborg Gudmundsdottir, Xiuqing Guo, Sarah E Harris, Keiko Hikino, Zhijie Huang, Christophe Lefevre, Leo-Pekka Lyytikäinen, Yuri Milaneschi, Giuseppe Giovanni Nardone, Aurora Santin, Helena Schmidt, Botong Shen, Tamar Sofer, Quan Sun, Ye An Tan, Jingxian Tang, Sébastien Thériault, Peter J Van Der Most, Erin B Ware, Stefan Weiss, Wang Ya Xing, Chenglong Yu, Wei Zhao, Md Abu Yusuf Ansari, Pramod Anugu, John R Attia, Lydia A Bazzano, Joshua C Bis, Max Breyer, Brian Cade, Guanjie Chen, Stacey Collins, Janie Corley, Gail Davies, Marcus Dörr, Jiawen Du, Todd L Edwards, Tariq Faquih, Jessica D Faul, Alison E Fohner, Amanda M Fretts, Srushti Gangireddy, Adam Gepner, Mariaelisa Graff, Edith Hofer, Georg Homuth, Michelle M Hood, Xu Jie, Mika Kähönen, Sharon L R Kardia, Carrie A Karvonen-Gutierrez, Lenore J Launer, Daniel Levy, Maitreiyi Maheshwari, Lisa W Martin, Koichi Matsuda, John J Mcneil, Ilja M Nolte, Tomo Okochi, Laura M Raffield, Olli T Raitakari, Lorenz Risch, Martin Risch, Ana Diez Roux, Edward A Ruiz-Narvaez, Tom C Russ, Takeo Saito, Pamela J Schreiner, Rodney J Scott, James Shikany, Jennifer A Smith, Harold Snieder, Beatrice Spedicati, E Shyong Tai, Adele M Taylor, Kent D Taylor, Paola Tesolin, Rob M Van Dam, Rujia Wang, Wei Wenbin, Tian Xie, Jie Yao, Kristin L Young, Ruiyuan Zhang, Alan B Zonderman, Biobank Japan Project, Lifelines Cohort Study, Maria Pina Concas, David Conen, Simon R Cox, Michele K Evans, Ervin R Fox, Lisa De Las Fuentes, Ayush Giri, Giorgia Girotto, Hans J Grabe, Charles Gu, Vilmundur Gudnason, Sioban D Harlow, Elizabeth Holliday, Jonas B Jost, Paul Lacaze, Seunggeun Lee, Terho Lehtimäki, Changwei Li, Ching-Ti Liu, Alanna C Morrison, Kari E North, Brenda W J H Penninx, Patricia A Peyser, Michael M Province, Bruce M Psaty, Susan Redline, Frits R Rosendaal, Charles N Rotimi, Jerome I Rotter, Reinhold Schmidt, Xueling Sim, Chikashi Terao, David R Weir, Xiaofeng Zhu, Nora Franceschini, Jeffrey R O'Connell, Cashell E Jaquish, Heming Wang, Alisa Manning, Patricia B Munroe, Dabeeru C Rao, Han Chen, W James Gauderman, Laura J Bierut, Thomas W Winkler, Myriam Fornage

Faculty, Staff and Student Publications

Gene-environment interactions may enhance our understanding of blood pressure (BP) biology. We conducted a meta-analysis of multi-population genome-wide association studies (GWASs) of BP traits accounting for gene-depressive symptomatology (DEPR) interactions. Our study included 564,680 adults from 67 cohorts and four population backgrounds: African (5%), Asian (7%), European (85%), and Hispanic (3%). We discovered seven previously unreported BP loci showing gene-DEPR interaction. These loci mapped to genes implicated in neurogenesis (TGFA and CASP3), lipid metabolism (ACSL1), neuronal apoptosis (CASP3), and synaptic activity (CNTN6 and DBI). We also showed evidence for gene-DEPR interaction at nine known BP loci, further suggesting links between …

Association Of Neighborhood Economic Trajectories And Risk Of Mortality Among Older Adults, Erika Figueroa-Solis, Qian Xiao

Faculty, Staff and Student Publications

Background

Lower neighborhood socioeconomic status (SES) and decline in neighborhood SES have been linked to detrimental health outcomes, such as cardiovascular disease (CVD), cancer, and mortality. However, few studies have investigated distinct types of neighborhood economic trajectories in relation to mortality. We examined the association between the recently developed multidimensional measure of neighborhood trajectories and mortality in older adults enrolled in the National Institutes of Health-AARP Diet and Health Study (NIH-AARP).

Methods

Neighborhoods were classified into five groups based on economic change patterns from 2000 to 2016 using American Community Survey data: Stability, Growth, Displacement, Abandonment, and Poverty Concentration. Mortality …

Characteristics And Effectiveness Of Maternal Health Interventions To Prevent Mother-To-Child Transmission (Pmtct) Of Syphilis In A Global Setting: A Scoping Review Using Intervention Mapping As A Framework, Jinni Tang, Anusha Sajja, Christine Markham, Emily T Hebert, Irene Stafford, Sheryl Dacso, Melissa F Peskin

Faculty, Staff and Student Publications

Background: Despite the availability of cost-effective treatments, maternal syphilis continues to contribute significantly to preventable stillbirths and congenital syphilis cases worldwide. This scoping review aimed to identify and characterize maternal health interventions designed to prevent mother-to-child transmission (PMTCT) of syphilis globally, using a modified Intervention Mapping (IM) framework.

Methods: We conducted a scoping review of maternal health interventions targeting PMTCT of syphilis published between January 2010 and August 2023. Searches were performed in PubMed, Medline Ovid, and Embase, supplemented by manual reference screening. Eligible studies described at least one maternal health intervention addressing syphilis PMTCT and were analyzed using a …

Fibrinogen-Associated Plasma Metabolites And Implications For Coagulation, Inflammation, And Vascular Diseases, Jayna C Nicholas, Taryn Alkis, Joshua C Bis, Eric Boerwinkle, Jennifer A Brody, Clary B Clish, Paul S De Vries, Yan Gao, Robert E Gerzsten, Xiuqing Guo, Andrew D Johnson, Martin G Larson, Rozenn N Lemaitre, Bruce M Psaty, Vasan Ramachandran, Alexander P Reiner, Stephen S Rich, Benjamin Rodriguez, Jian Rong, Jerome I Rotter, Jeanette Simino, Nicholas L Smith, James Wilson, Jie Yao, Alanna C Morrison, Bing Yu, Laura M Raffield

Faculty, Staff and Student Publications

Background: Fibrinogen is a critical coagulation factor that plays an essential role in thrombosis and is elevated in individuals with chronic inflammation. Here, we used fibrinogen as a representative quantitative measure of pro-coagulant risk and evaluated metabolites associated with fibrinogen levels through non-targeted plasma metabolomic profiling (Broad and Metabolon platforms).

Methods: Our analysis included 10,533 individuals across six U.S. based cohorts representing diverse population groups. The cross-sectional relationship between each of 789 tested metabolites and plasma fibrinogen concentration was assessed with adjustment for relevant covariates such as age, sex, body mass index, and circulating lipoprotein levels.

Results: Meta-analysis of per-cohort …

Cost-Effectiveness Of Home-Based Self-Sampling Vs Clinician Sampling For Anal Precancer Screening, Haluk Damgacioglu, Timothy L Mcauliffe, Timothy J Ridolfi, Elizabeth Chiao, Maria E Fernandez, Vanessa Schick, Jennifer S Smith, Bridgett Brzezinski, Jenna Nitkowski, Ashish A Deshmukh, Alan G Nyitray

Faculty, Staff and Student Publications

Importance: Anal cancer screening is recommended for high-risk populations, particularly sexual and gender minority (SGM) individuals. However, the cost-effectiveness of home-based self-sampling in increasing anal cancer screening uptake has not yet been evaluated in the US.

Objective: To evaluate the cost-effectiveness of home-based anal self-sampling compared with clinic-based screening among SGM individuals.

Design, setting, and participants: This economic evaluation used data from a 2-group randomized clinical trial conducted in Milwaukee, Wisconsin, from January 2020 to August 2022, enrolling SGM individuals aged 25 years or older. Participants were randomized to home-based self-sampling or clinic-based screening. Costs for home-based screening were obtained …

Genome-Wide Gene-Sleep Interaction Study Identifies Novel Lipid Loci In 732,564 Participants, Raymond Noordam, Wenyi Wang, Pavithra Nagarajan, Heming Wang, Michael R Brown, Amy R Bentley, Qin Hui, Aldi T Kraja, John L Morrison, Jeffrey R O'Connel, Songmi Lee, Karen Schwander, Traci M Bartz, Lisa De Las Fuentes, Mary F Feitosa, Xiuqing Guo, Xu Hanfei, Sarah E Harris, Zhijie Huang, Mart Kals, Christophe Lefevre, Massimo Mangino, Yuri Milaneschi, Peter J Van Der Most, Natasha L Pacheco, Nicholette D Palmer, Varun Rao, Rainer Rauramaa, Quan Sun, Yasuharu Tabara, Dina Vojinovic, Yujie Wang, Stefan Weiss, Qian Yang, Wei Zhao, Wanying Zhu, Md Abu Yusuf Ansari, Hugues Aschard, Pramod Anugu, Themistocles L Assimes, John Attia, Laura D Baker, Christie Ballantyne, Lydia Bazzano, Eric Boerwinkle, Brain Cade, Hung-Hsin Chen, Wei Chen, Yii-Der Ida Chen, Zekai Chen, Kelly Cho, Ileana De Anda-Duran, Latchezar Dimitrov, Anh Do, Todd Edwards, Tariq Faquih, Aroon Hingorani, Susan P Fisher-Hoch, J Michael Gaziano, Sina A Gharib, Ayush Giri, Mohsen Ghanbari, Hans Jörgen Grabe, Mariaelisa Graff, C Charles Gu, Jiang He, Sami Heikkinen, James Hixson, Yuk-Lam Ho, Michelle M Hood, Serena C Houghton, Carrie A Karvonen-Gutierrez, Takahisa Kawaguchi, Tuomas O Kilpeläinen, Pirjo Komulainen, Henry J Lin, Gregorio V Linchangco, Annemarie I Luik, Jintao Ma, James B Meigs, Joseph B Mccormick, Cristina Menni, Ilja M Nolte, Jill M Norris, Lauren E Petty, Hannah G Polikowsky, Laura M Raffield, Stephen S Rich, Renata L Riha, Thomas C Russ, Edward A Ruiz-Narvaez, Colleen M Sitlani, Jennifer A Smith, Harold Snieder, Tamar Sofer, Botong Shen, Jingxian Tang, Kent D Taylor, Maris Teder-Laving, Rima Triatin, Michael Y Tsai, Henry Völzke, Kenneth E Westerman, Rui Xia, Jie Yao, Kristin L Young, Ruiyuan Zhang, Alan B Zonderman, Xiaofeng Zhu, Jennifer E Below, Simon R Cox, Michelle Evans, Myriam Fornage, Ervin R Fox, Nora Franceschini, Sioban D Harlow, Elizabeth Holliday, M Arfan Ikram, Tanika Kelly, Timo A Lakka, Deborah A Lawlor, Changwei Li, Ching-Ti Liu, Reedik Mägi, Alisa K Manning, Fumihiko Matsuda, Alanna C Morrison, Matthias Nauck, Kari E North, Brenda Wjh Penninx, Michael A Province, Bruce M Psaty, Jerome I Rotter, Tim D Spector, Lynne E Wagenknecht, Ko Willems Van Dijk, Lifelines Cohort Study, Million Veteran Program, Cashell E Jaquish, Peter Wf Wilson, Patricia A Peyser, Patricia B Munroe, Paul S De Vries, W James Gauderman, Yan V Sun, Han Chen, Clint L Miller, Thomas W Winkler, Dabeeru C Rao, Susan Redline, Diana Van Heemst

Faculty, Staff and Student Publications

Background and aims: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets.

Methods: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) …

De Novo And Inherited Dominant Variants In U4 And U6 Snrna Genes Cause Retinitis Pigmentosa, Mathieu Quinodoz, Kim Rodenburg, Zuzana Cvackova, Karolina Kaminska, Suzanne E De Bruijn, Ana Belén Iglesias-Romero, Erica G M Boonen, Mukhtar Ullah, Nick Zomer, Marc Folcher, Jacques Bijon, Lara K Holtes, Stephen H Tsang, Zelia Corradi, K Bailey Freund, Stefanida Shliaga, Daan M Panneman, Rebekkah J Hitti-Malin, Manir Ali, Ala'a Altalbishi, Sten Andréasson, Georg Ansari, Gavin Arno, Galuh D N Astuti, Carmen Ayuso, Radha Ayyagari, Sandro Banfi, Eyal Banin, Tahsin Stefan Barakat, Mirella T S Barboni, Miriam Bauwens, Tamar Ben-Yosef, Virginie Bernard, David G Birch, Pooja Biswas, Fiona Blanco-Kelly, Beatrice Bocquet, Camiel J F Boon, Kari Branham, Dominique Bremond-Gignac, Alexis Ceecee Britten-Jones, Kinga M Bujakowska, Cyril Burin Des Roziers, Elizabeth L Cadena, Giacomo Calzetti, Francesca Cancellieri, Luca Cattaneo, Naomi Chadderton, Peter Charbel Issa, Luísa Coutinho-Santos, Stephen P Daiger, Elfride De Baere, Marieke De Bruyne, Berta De La Cerda, John N De Roach, Julie De Zaeytijd, Ronny Derks, Claire-Marie Dhaenens, Lubica Dudakova, Jacque L Duncan, G Jane Farrar, Nicolas Feltgen, Beau J Fenner, Lidia Fernández-Caballero, Juliana M Ferraz Sallum, Simone Gana, Alejandro Garanto, Jessica C Gardner, Christian Gilissen, Roser Gonzàlez-Duarte, Kensuke Goto, Sam Griffiths-Jones, Tobias B Haack, Lonneke Haer-Wigman, Alison J Hardcastle, Takaaki Hayashi, Elise Héon, Lies H Hoefsloot, Alexander Hoischen, Josephine P Holtan, Carel B Hoyng, Manuel Benjamin B Ibanez, Chris F Inglehearn, Takeshi Iwata, Brynjar O Jensson, Kaylie Jones, Vasiliki Kalatzis, Smaragda Kamakari, Marianthi Karali, Ulrich Kellner, Caroline C W Klaver, Krisztina Knézy, Robert K Koenekoop, Susanne Kohl, Taro Kominami, Laura Kühlewein, Tina M Lamey, Rina Leibu, Bart P Leroy, Petra Liskova, Irma Lopez, Victor R De J López-Rodríguez, Quinten Mahieu, Omar A Mahroo, Gaël Manes, Luke Mansard, M Pilar Martín-Gutiérrez, Nelson Martins, Laura Mauring, Martin Mckibbin, Terri L Mclaren, Isabelle Meunier, Michel Michaelides, José M Millán, Kei Mizobuchi, Rajarshi Mukherjee, Zoltán Zsolt Nagy, Kornelia Neveling, Monika Ołdak, Michiel Oorsprong, Yang Pan, Anastasia Papachristou, Antonio Percesepe, Maximilian Pfau, Eric A Pierce, Emily Place, Raj Ramesar, Francis Ramond, Florence Andrée Rasquin, Gillian I Rice, Lisa Roberts, María Rodríguez-Hidalgo, Javier Ruiz-Ederra, Ataf H Sabir, Ai Fujita Sajiki, Ana Isabel Sánchez-Barbero, Asodu Sandeep Sarma, Riccardo Sangermano, Cristina M Santos, Margherita Scarpato, Hendrik P N Scholl, Dror Sharon, Sabrina G Signorini, Francesca Simonelli, Ana Berta Sousa, Maria Stefaniotou, Kari Stefansson, Katarina Stingl, Akiko Suga, Patrick Sulem, Lori S Sullivan, Viktória Szabó, Jacek P Szaflik, Gita Taurina, Alberta A H J Thiadens, Carmel Toomes, Viet H Tran, Miltiadis K Tsilimbaris, Pavlina Tsoka, Veronika Vaclavik, Marie Vajter, Sandra Valeina, Enza Maria Valente, Casey Valentine, Rebeca Valero, Sophie Valleix, Joseph Van Aerschot, L Ingeborgh Van Den Born, Mattias Van Heetvelde, Virginie J M Verhoeven, Andrea L Vincent, Andrew R Webster, Laura Whelan, Bernd Wissinger, Georgia G Yioti, Kazutoshi Yoshitake, Juan C Zenteno, Roberta Zeuli, Theresia Zuleger, Chaim Landau, Allan I Jacob, Siying Lin, Frans P M Cremers, Winston Lee, Jamie M Ellingford, David Stanek, Susanne Roosing, Carlo Rivolta

Faculty, Staff and Student Publications

Small nuclear RNAs (snRNAs) combine with specific proteins to generate small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. U4 snRNA forms a duplex with U6 and, together with U5, contributes to the tri-snRNP spliceosomal complex. Variants in RNU4-2, which encodes U4, have recently been implicated in neurodevelopmental disorders. Here we show that heterozygous inherited and de novo variants in RNU4-2 and in four RNU6 paralogs (RNU6-1, RNU6-2, RNU6-8 and RNU6-9), which encode U6, recur in individuals with nonsyndromic retinitis pigmentosa (RP), a genetic disorder causing progressive blindness. These variants cluster within the three-way junction of the U4/U6 duplex, …

Geospatial Disparities In Adolescent Mental Health Resources: School- And Community-Level Evidence From Travis County, Texas, Sharon V Munroe, Jingjing Gao, Gayla Ferguson, Muinat Abolore Idris, Eric C Jones

Faculty, Staff and Student Publications

Background: Adolescents in the United States face growing mental health challenges, with nearly one in three high school students reporting poor mental health in the past 30 days. Schools increasingly serve as key access points for mental health care. However, geographic disparities in access to school-based mental health services remain underexplored.

Purpose: This study examines the spatial distribution of adolescent mental health resources in Travis County, Texas, and evaluates how school- and community-level factors are associated with the presence of on-site school social workers.

Methods: School locations, enrollment data, and the presence of on-site social workers were mapped and analyzed …

Understanding Ehlers-Danlos Syndrome: A Claims-Based Analysis Of Healthcare Cost Patterns, Samson A Oyediran, Youngran Kim, Zhanna Novikov, Trudy M Krause

Faculty, Staff and Student Publications

Background: Ehlers-Danlos Syndrome (EDS) is a rare connective tissue disorder associated with substantial clinical complexity and healthcare utilization. Despite increasing recognition of EDS, little is known about its economic burden in the United States.

Objective: To assess the all-cause healthcare costs for individuals with newly diagnosed EDS during the pre-diagnosis year and the first 2 years post-diagnosis.

Methods: A retrospective cohort study was conducted using the Merative™ MarketScan® Commercial Claims and Encounters Database (2016-2022). Newly diagnosed patients were identified using ICD-10-CM codes, with the first observed diagnosis defined as the index date. Continuous enrollment for 12 months pre-index and 24 …

Latent Classification Of Time-Dependent Transition Rates In Longitudinal Binary Outcome Data, Joonha Chang, Wenyaw Chan

Faculty, Staff and Student Publications

Continuous-time Markov chain (CTMC) models and latent classification methods are commonly used to analyze longitudinal categorical outcomes in medical research. While CTMC models are popular for their simplicity and effectiveness, their assumption of constant transition rates presents limitations in capturing dynamic behaviors. To address this, non-homogeneous continuous-time Markov chains (NH-CTMCs) have been developed, incorporating time-varying transition rates to enhance model flexibility. In this study, we leverage closed-form transition probabilities for a fully ergodic two-state NH-CTMC model and propose a latent class clustering approach to identify heterogeneous transition rate patterns within the population. We emphasize the potential advantages of these models …

“If He Did It, I Can Do It, Too. I Can Change My Life Around”: The Social Model Of Recovery Within The Context Of Recovery Homes Accepting Residents Prescribed Medications For Opioid Use Disorder, Jodie M Dewey, Kathryn R Gallardo, Meenakshi S Subbaraman, Amy A Mericle

Faculty, Staff and Student Publications

Introduction: This paper provides an in-depth examination of examines four recovery residences, that serve individuals prescribed medications for opioid use disorder (MOUD). The study has two primary aims: first, to deepen understanding of how recovery residences adopt and operationalize Social Model of Recovery principles; and second, to identify gaps in staff integration of residents receiving MOUD-gaps that may either support or undermine the integrity of the social model within these settings.

Methods: We conducted semi-structured interviews with 17 residents receiving MOUD living in four participating recovery homes. The interviews were conducted between August 2022 and January 2024 using a semi-structured …

Corrigendum To 'Continuous Vital Sign Monitoring On Surgical Wards: The Cosmos Pilot, Nikola Anusic, Alper Gulluoglu, Elyad Ekrami, Edward J Mascha, Shuyi Li, René Coffeng, Alparslan Turan, Amber Clemens, Christine Perez, John W Beard, Daniel I Sessler, Cosmos Pilot Investigators

Faculty, Staff and Student Publications

Study objectives: Alerts for vital sign abnormalities seek to identify meaningful patient instability while limiting alarm fatigue. Optimal vital sign alarm settings for postoperative patients remain unknown, as is whether alerts lead to effective clinical responses reducing vital sign disturbances. We conducted a 2-phase pilot study to identify thresholds and delays and test the hypothesis that alerts from continuous monitoring reduce the duration of vital sign abnormalities.

Design: Two-phase pilot.

Patients: 250 adults having major non-cardiac surgery.

Setting: Surgical wards.

Intervention: All patients had routine vital sign monitoring by nurses at 4-h intervals. We initially continuously recorded clinician-blinded saturation, heart …

Pregnancy And Breastfeeding Are Associated With Less Later-Life Cognitive Decline In A Longitudinal, Prospective Cohort, Molly M Fox, Jennifer E Bramen, Dayoon Kwon, Mark A Espeland, Yijia Sun, Li Zhang, Aladdin H Shadyab, Ramon Casanova, Joann E Manson, Marcus Y Chang, Verna R Porter, Leslie V Farland, Qian Xiao, Robert A Wild, Prabha Siddarth, Carolyn J Crandall

Faculty, Staff and Student Publications

Introduction: The brains of female mammals evolved to undergo structural and functional changes during pregnancy and lactation, equipping them for motherhood. However, long-term cognitive health implications of these adaptations in women are poorly understood.

Methods: In the Women's Health Initiative (WHI) Memory Study (WHIMS; n = 7427) and WHI Study of Cognitive Aging (WHISCA; n = 2304), postmenopausal women completed reproductive history interviews, annual global cognitive assessment from mean age 70 for up to 13 years, and multi-domain cognitive testing for up to 8 years.

Results: Each additional month pregnant was associated with higher scores of global cognition. Each additional …

Artificial Light At Night Extends Pollen Season And Elevates Allergen Exposure, Brandt Geist, Lin Meng, Daniel S W Katz, Huidong Li, Franz Hölker, Qian Xiao

Faculty, Staff and Student Publications

Artificial light at night (ALAN), a growing environmental stressor in urban ecosystems, disrupts natural light-dark cycles and alters plant phenological events such as leaf-out and flowering. However, the extent to which ALAN influences airborne pollen season timing and exacerbates allergy-related health risks remains largely understudied. This study investigates how ALAN influences the timing and duration of the airborne pollen season across the Northeastern United States from 2012 to 2023 and the consequences of allergenic pollen exposure. Using daily pollen concentrations from the National Allergy Bureau, ALAN data from the Visible Infrared Imaging Radiometer Suite product, and gridded Daymet climate data, …

Plasma Proteomic Profile Of Dietary Potassium And Incident Ckd, Jiaqi Yang, Lauren Bernard, Jingsha Chen, Valerie K Sullivan, Bing Yu, Eugene P Rhee, Paul A Welling, Casey M Rebholz

Faculty, Staff and Student Publications

Background:: There is a need for objective biomarkers of dietary potassium. The mechanisms through which dietary potassium influences kidney health are incompletely understood.

Methods:: Atherosclerosis Risk in Communities study participants at visit 3 (1993–1995) with dietary and proteomics data were randomly divided into discovery (N=6,814) and replication (N=3,380) sets. We examined associations between dietary potassium and 4,955 aptamers using multivariable linear regression, adjusting for sociodemographic factors, health behaviors, and estimated glomerular filtration rate, with a false discovery rate of 0.05. Then, we tested the prospective associations between potassium-related proteins and incident chronic kidney disease (CKD).

Results:: …

Examining Tobacco Prevention And Cessation Among Dental Students In Southern Italy, Olga Di Fede, Samuel Tundealao, David Okuji, Gaetano La Mantia, Irene Tamí-Maury

Faculty, Staff and Student Publications

Background: Previous studies have reported that tobacco use among healthcare providers (HCPs) has a negative impact on their beliefs and attitudes toward tobacco prevention and control measures. However, little is known about these among Italian dental students. Therefore, this single-site study examined tobacco use behaviors and the knowledge, attitudes, and perceptions of dental students at a public university in Southern Italy regarding tobacco prevention and control.

Methods: A cross-sectional study through an online survey was conducted among 115 students aged 18 + years enrolled in dentistry and dental hygiene programs at a Southern Italy university. Chi-squared, Fisher's, t-tests, and …

Adapting A Smartphone-Based Auricular Point Acupressure Self-Management Program For Rural Chronic Musculoskeletal Pain: Qualitative Study, Jungkyung Min, Peiyin Hung, Jane N Bolin, Rupsikha Bora, Sarah Pace, Patricia Pitones, Hulin Wu, Jennifer Kawi

Faculty, Staff and Student Publications

Background: Chronic musculoskeletal pain is more prevalent in rural areas where access to pain interventions, including complementary approaches like Auricular Point Acupressure (APA), remains limited. APA is a non-invasive, needle-free approach, and its smartphone-based self-management delivery model has not been optimized for rural contexts.

Objectives: To explore the perspectives of rural partners on adapting a smartphone-based Auricular Point Acupressure-Self-Management (APA-SM) program to better meet rural needs. Study objectives were to: (1) refine the APA-SM program for rural adults, (2) identify implementation barriers, (3) understand practice workflows and engagement, and (4) identify strategies to integrate the APA-SM program into rural pain …

Subgroup Identification Of Disparities In Buprenorphine Discontinuation In Opioid-Use Disorder: A Virtual Twins Machine Learning Approach Using Nationwide United States Claims Data, 2006–2022, Kehe Zhang, Paula A Jaimes-Buitron, Wanru Guo, Yanmin Gong, Yuanxiong Guo, Carolina Vivas Valencia, Cici Bauer

Faculty, Staff and Student Publications

Buprenorphine retention is crucial for effective treatment of opioid use disorder (OUD), yet disparities in treatment discontinuation persist. This study aims to identify and quantify disparities in buprenorphine treatment retention using a machine learning framework adapted from Virtual Twins approach focusing on disparities related to sex, age, insurance type, geographic region, mental health status and community-level Social Vulnerability Index (SVI). Using a nationwide longitudinal cohort, we applied a two-stage machine learning approach. In Stage one, we trained classification models to estimate the counterfactual differences in treatment discontinuation across disparity types. Model performance was assessed using C-statistics and precision-recall curve. In …