Digital Commons Network^™

Identifying Sex- And Gender-Specific Endocrinological, Lifestyle, Psychosocial, And Socio-Cultural Targets For Alzheimer's Disease Prevention In Africans: The Female Brain Health And Endocrine Research In Africa (Fember-Africa) Project, Chinedu Momoh, Benard Aliwa, Lukoye Atwoli, Karen Blackmon, Edna Bosire, Samuel Gitau, Harrison Kaleli, Ciru Kamanda, Linda Khakali, Rachel Maina, Peter Mativo, Sylvia Mbugua, Zul Merali, Kendi Muchungi, Anne Njogu, Douglas Nyankira, Alice Ondieki, Catherine Onyancha, Stanely Onyango, Jasmit Shah, Sheena Shah, Cynthia Smith, Dilraj Sokhi, Sheila Waa, Thomas Thesen

Brain and Mind Institute

Dementia rates are rising globally, with the burden increasing most rapidly in low- tomiddle-income countries. Despite this, research into Alzheimer’s disease and relateddementias (ADRD) among African populations remains limited, with existing modelsbased on Western cohorts that overlook sex-, gender-, and ancestry-specific factors.The Female Brain Health and Endocrine Research in Africa (FemBER-Africa) project,hosted at the Brain and Mind Institute, Aga Khan University, Kenya, will establish adeeply phenotyped cohort of 250 African individuals across the ADRD spectrum. Itwill assess sex-specific risk factors linked to ethnicity, lifestyle, and endocrinologicalvariables using fluid-based biomarkers (blood and saliva), neuroimaging (magneticresonance imaging and positron emission tomography), and …

Prevalence And Determinants Of Nomophobia Among Healthcare Workers In Nepal: A Cross-Sectional Study, Prakash Banjade, Asmita Itani, Munish Sharma, Reena Shah, Jasmit Shah, Aakansha Singh, Rahul Kashyap, Salim Surani

Brain and Mind Institute

Introduction: Nomophobia, the fear of being without a mobile phone, has become a significant concern in the current digital age. Healthcare professionals rely heavily on mobile devices for communication and information access. This cross-sectional study aimed to assess the prevalence and determinants of nomophobia among healthcare workers in Nepal.

Methods: A modified Nomophobia Questionnaire (NMP-Q) was used to determine nomophobia scores. Demographic characteristics such as age, gender, race, type of smartphone, hours spent on a smartphone, and type of medical specialty were considered to evaluate nomophobia in diverse groups of healthcare workers. Summary statistics were presented as frequencies …

Evaluating The Impact Of Alcohol On Dementia: Evidence From 13 Developing Countries, Cyprian Mostert

Brain and Mind Institute

Background: The 2024 Lancet Commission on Dementia Prevention identified alcoholconsumption as a risk factor contributing to a global increase in dementia cases by onepercent.

Method: We used a panel VAR model to analyze the impact of alcohol consumption ondementia prevalence in 13 developing countries with different alcohol tax systems.

Result: In countries with progressive alcohol tax systems, an increase in taxes onbeer and spirits leads to a 10 percent reduction in per capita alcohol consumption.This decline corresponds to a 4 percent reduction in dementia prevalence within fouryears. In countries with hybrid alcohol tax systems, a combination of alcohol bansand tax …

Recovery As Relational Care: Integrating Policy, Education, And Community Resilience In Rural Appalachia, Jon Dance, Josh Thompson

The Rural Educator

Despite national media attention and significant policy investment, substance use epidemics continue to impact Central Appalachia. Inequities affecting rural communities and persistent stigma create significant barriers to well-being and recovery. Recovery, however, is more than a healthcare issue; it is a relational and community-rooted process that must involve education, policy, and care. In this article, we reframe deficit-oriented conceptions of recovery to highlight the vital role of relational care and community collaboration in promoting wellness in rural Appalachia. We offer the Community Resiliency Model (CRM) as a practical, evidence-informed strategy to foster emotional regulation, coregulation, and community resilience. We call …

Trump’S Multi-Pronged Attack On Renewable Energy, Michael B. Gerrard

Faculty Scholarship

Federal policy on renewable energy took a 180-degree turn on the day of Donald Trump’s second inauguration. The Biden administration had rightly seen a massive expansion of clean energy, especially wind and solar and the associated storage and transmission, as key to moving away from fossil fuels and fighting climate change. But Mr. Trump denies that climate change is a serious problem and works to increase both the supply of and the demand for fossil fuels.

This article discusses the range of actions involved in the Trump administration’s attack on renewable energy.

Leaving Delaware? The Essential Role Of Specialized Corporate Courts, Zohar Goshen, Tomer S. Stein

Faculty Scholarship

Following the Delaware Court of Chancery’s invalidation of Elon Musk’s fifty-six- billion-dollar compensation package, Tesla moved its incorporation from Delaware to Texas. Shortly thereafter, Delaware’s legislature, seeking to protect Delaware’s dominant incorporation position, passed the most sweeping corporate law amendments in fifty years.

Both supporters of Musk and defenders of Delaware’s judiciary have accused each other of partisanship, but neither side has addressed the central question: What is the role of specialized corporate courts?

This Essay presents a novel theory of why such courts are necessary. Corporate disputes are distinct because they arise within ongoing relationships between shareholders and management, …

Ai Companions And The Lessons Of Family Law, Clare Huntington

Faculty Scholarship

Virtual friends and lovers powered by artificial intelligence are rapidly moving to the center of our emotional and social lives. Millions of people turn to AI companions every day for conversation, romance, sexual intimacy, therapy, and education. AI companionship holds promise, potentially reducing loneliness, supporting people without access to mental health treatment, helping students learn, and offering a judgment-free space for sensitive conversations. But AI companionship also raises significant concerns. The technology's addictiveness may exacerbate loneliness and can undermine human relationships. Therapy bots may prove more harmful than helpful. AI companions can be emotionally abusive. And their access to the …

The Constitutional Fight Over The Nlra And The Nlrb: A 90 Year Reprise, Kate Andrias

Faculty Scholarship

This article traces renewed constitutional challenges to the National Labor Relations Act (NLRA) and the National Labor Relations Board (NLRB), placing them in historical and doctrinal context. Contemporary attacks — advanced by major corporations and the Trump Administration — revive the constitutional conflicts of the 1930s. Drawing on arguments rooted in the unitary executive theory, as well as Article III and the Seventh Amendment, the current challenges threaten not only the NLRB’s independence but the broader administrative state and the system of labor rights it sustains. At stake is more than institutional design: the dispute reflects a deeper contest over …

Can Interpersonal Trust Predict And Account For Symptom Change During Group Cognitive Processing Therapy For Ptsd? An Investigation Of The Iterated Trust Game, M Wright Williams, Christopher Hunt, David P Graham, Matt Estey, Lia Smith, Katherine Mccurry, Brooks King-Casas, Pearl Chiu

Faculty, Staff and Students Publications

Objective: Group cognitive processing therapy (GCPT) is frequently utilized to treat PTSD within the VA healthcare system, but its mechanisms are not well understood. Interpersonal trust could be an important change process in GCPT given its relevance to group-based therapy and its role in CPT, but self-report measures are inadequate for capturing the dynamic interplay that defines interpersonal trust. Here, we examined the degree to which interpersonal could predict and account for PTSD symptom change in GCPT using the iterated trust game (ITG)-a behavioral task used to approximate real-world trust behavior.

Methods: Participants were Veterans with PTSD who participated in …

Clonal Hematopoiesis And Subsequent Venous Thromboembolism Among Survivors Of Autologous Transplantation For Lymphoma, Radhika Gangaraju, Yanjun Chen, Lindsey Hageman, Alysia Bosworth, Elizabeth Ross, Liton Francisco, Purnima Singh, Melissa A Richard, Chengcheng Yan, Rashi Kalra, Changde Cheng, Saro H Armenian, Stephen J Forman, Ravi Bhatia, Smita Bhatia

Faculty, Staff and Students Publications

Clonal hematopoiesis is associated with increased risk of venous thromboembolism (VTE). The risk of VTE is high in patients with lymphoma and after autologous peripheral blood stem cell transplantation, and clonal hematopoiesis is present in many patients with lymphoma at autologous peripheral blood stem cell transplantation. We examined whether clonal hematopoiesis increases posttransplant VTE risk in patients with lymphoma. Our study included 557 patients with lymphoma who had survived 2 or more years after receiving autologous peripheral blood stem cell transplantation between 1999 and 2014. Clonal hematopoiesis was measured by targeted sequencing of cryopreserved peripheral blood stem cell product. Median …

Neurodevelopmental Abnormalities Underlying Behavioral Deficits In A Model Of Pediatric Obstructive Sleep Apnea, Arvind Chandrakantan, Michael R Williamson, Vaishnav Krishnan, Mahyar J Hedayatpour, Adam C Adler, Nandani Adyapak, Chris S Ward, Russell Ray, David Durgan, Farrah Kheradmand, Benjamin Deneen

Faculty, Staff and Students Publications

Rationale: Pediatric Obstructive Sleep Apnea (POSA) is a relatively common childhood sleep disorder whose neurodevelopmental phenotype includes deficits in learning and memory, olfaction, and fine motor abilities.

Objectives: To date, there has not been a validated preclinical model of POSA, hampering efforts in understanding how nocturnal episodes of intermittent hypoxia disrupt neurodevelopmental trajectories. The objective of this study was to create a faithful sculpting of the human condition in a preclinical murine model.

Methods: We used clinical data from children with POSA to develop and validate a mouse model of POSA that faithfully recapitulates several behavioral deficits seen in the …

Inhibition Of Bmper Mitigates Pulmonary Hypertension By Modulating Lrp1-Yap Interaction In Smooth Muscle Cells, Hua Mao, Claire M Li, Bing Sun, Christopher S Ward, Alan R Waich-Cohen, Ivan O Rosas, Howard J Huang, Harry Karmouty-Quintana, Liang Xie, Lavannya M Pandit, Xinchun Pi

Faculty, Staff and Students Publications

Background: BMPER (bone morphogenetic protein-binding endothelial regulator) is a secreted protein that is highly expressed in endothelial cells. It regulates the BMP (bone morphogenetic protein) pathway during vascular development and adulthood. Mutations in the BMP pathway are recognized as risk factors for pulmonary arterial hypertension group 1 pulmonary hypertension (PH). However, the roles of BMPER in pulmonary arterial hypertension remain unknown.

Methods: We assessed BMPER expression in Group 1 pulmonary arterial hypertension patient samples and examined its role in vascular remodeling using in vivo and in vitro approaches.

Results: BMPER level was elevated in pulmonary arterial hypertension lungs and significantly …

Call To Action-Pediatric Masld Requires Immediate Attention To Curb Health Crisis, Phillipp Hartmann, Marialena Mouzaki, Sara Hassan, Mohit Kehar, Krupa R Mysore, Erin Mauney, Dieudonne Nonga, Sara Karjoo, Shilpa Sood, Andrea Tou, Christine Brichta, Rachel E Herdes, Nikhil Pai, Donna K Garner, Mary E Rinella, Mazen Noureddin, Zobair Younossi, Alina M Allen, Arun Sanyal, Taisa Kohut, Rohit Kohli, Charina M Ramirez, Stavra Xanthakos, Miriam B Vos, Jeffrey B Schwimmer, Samar H Ibrahim, Jennifer Panganiban

Faculty, Staff and Students Publications

Pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) has become more prevalent on a global scale over the last decades and is associated with significant comorbidities in childhood and a 40-fold higher risk of early mortality in young adulthood. MASLD has now become the leading indication for liver transplantation in young adults in the United States. However, pediatric MASLD is still perceived as an indolent condition by many patients, families, and clinicians. In this Call to Action, we aim to raise awareness of pediatric MASLD as a public health crisis. Herein, we describe insufficient screening and disease staging practices, and a …

Predicting Craving-Related Emotions Among Opioid Use Disorder Patients: Preliminary Results, Zachary King, Zoe Setiadi, Liana Hamdan, Hajar Ahmed, Bishal Lamichhane, Ashutosh Sabharwal, Ramiro Salas, Nidal Moukaddam, Akane Sano

Faculty, Staff and Students Publications

Individuals with Opioid Use Disorder (OUD) often struggle to maintain sobriety, with many experiencing relapse within the first year. While medication-assisted treatment (MAT) is among the most effective approaches, access to intensive care is often limited by financial barriers. Mobile health (mHealth) technologies offer a promising, cost-effective alternative by enabling continuous monitoring and timely intervention through tools such as ecological momentary assessments (EMAs), wearable sensors, and smartphone data. In this study, we explore the feasibility of using mHealth data to predict emotions that align with cravings in OUD patients undergoing MAT. Using data collected from EMAs, wearables, smartphone tracking, and …

Targeting The Hippo Pathway For Cardiac Regeneration, Rich Gang Li, Fansen Meng, James F Martin

Faculty, Staff and Students Publications

Ischemic heart disease, which affects more than 200 million people worldwide, is caused by reduced blood flow to the heart and leads to widespread cardiomyocyte death. Due to the limited regenerative potential of cardiomyocytes, the lost tissue is replaced by a fibrotic scar, resulting in reduced cardiac function and progression to heart failure. Current therapeutic interventions aim to improve blood flow but cannot address the inability of cardiomyocytes to renew after injury. However, multiple studies have shown that modulating the Hippo signaling pathway to activate Yes-associated protein (YAP), a transcription coactivator, in adult murine and porcine cardiomyocytes induces robust cardiomyocyte …

Management Of Patients With Heart Failure At High Risk Of Hyperkalaemia: The Care-Hk In Hf Registry, Stephen J Greene, Andrew J Sauer, Michael Böhm, Biykem Bozkurt, Javed Butler, John G F Cleland, Andrew J S Coats, Nihar R Desai, Diederick E Grobbee, Ellie Kelepouris, Fausto Pinto, Giuseppe Rosano, Victoria Donachie, Solenn Fabien, Sandra Waechter, Maria G Crespo-Leiro, Martin Hülsmann, Tibor Kempf, Otmar Pfister, Anne-Catherine Pouleur, Manish Saxena, Martin Schulz, Maurizio Volterrani, Stefan D Anker, Mikhail N Kosiborod

Faculty, Staff and Students Publications

Aims: Patients with heart failure (HF) at high risk for hyperkalaemia are underrepresented in prospective HF registries. The CARE-HK in HF registry sought to characterize prospectively the clinical profile, management, and outcomes for patients with HF at high risk of hyperkalaemia.

Methods and results: CARE-HK in HF was a multinational prospective registry of outpatients with HF (regardless of left ventricular ejection fraction [LVEF]) treated with an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker/angiotensin receptor-neprilysin inhibitor (ACEI/ARB/ARNI) and either receiving or potential candidate for a mineralocorticoid receptor antagonist (MRA). All patients were at increased risk of hyperkalaemia, defined as hyperkalaemia at baseline, …

Ambulatory Acute Kidney Injury In Patients With Cirrhosis Is Common And Burdensome, Kavish R Patidar, Ruben Hernaez, Yan Liu, George Cholankeril, Jennifer R Kramer, Thom Taylor, Prasun Jalal, Tzu-Hao Lee, Avegail G Flores, Giuseppe Cullaro, Andrew S Allegretti, Pere Gines, Fasiha Kanwal

Faculty, Staff and Students Publications

Background & aims: Little is known about ambulatory acute kidney injury (A-AKI), which develops in an outpatient setting.

Methods: We conducted a retrospective cohort study of patients diagnosed with cirrhosis between January 1, 2018, and December 31, 2019 from 130 hospitals in the Veterans Affairs healthcare system. Patients were classified as having incident A-AKI if they met the International Club of Ascites AKI criteria in an outpatient setting. We used multivariable regression models to identify factors associated with A-AKI development within 1 year of cirrhosis diagnosis. We also conducted a structured implicit review of patients' medical charts to determine the …

Targeting Rbm10-Repressed Rorb Activity In Liquid Condensates Inhibits Lysosomal Biogenesis And Neuroblastoma Progression Via Affecting Nf-Κb Signaling, Yanhua Guo, Xiaojing Wang, Chunhui Yang, Zhijie Wang, Xiaolin Wang, Xinyue Li, Jiaying Qu, Shunchen Zhou, Liduan Zheng, Qiangsong Tong

Faculty, Staff and Students Publications

Neuroblastoma (NB), a pediatric solid malignancy, is distinguished by hetergenous clinical characteristics, including tumor aggressiveness or spontaneous regression. Nevertheless, the regulatory mechanisms and therapeutic approaches underlying these processes are still mainly unknown. Herein, RAR-related orphan receptor B (RORB) as a transcription factor repressing nuclear factor kappa B (NF-κB) signaling involved in lysosomal biogenesis of NB. RORB attenuated the growth, invasiveness, and metastatic spread of NB cells are identified. From a mechanistic perspective, RORB increased the transcription of nuclear receptor subfamily 1 group D member 1 (NR1D1)- or RIO kinase 3 (RIOK3)- in a circadian clock-dependent manner, resulting in suppression of …

Upregulation Of Adenosine A2a Receptor In Astrocytes Is Sufficient To Trigger Hippocampal Multicellular Dysfunctions And Memory Deficits, Agathe Launay, Miranda E Orr, Et Al.

2020-Current year OA Pubs

Adenosine is an ubiquitous neuromodulator that ensures cerebral homeostasis. It exerts numerous functions through the activation of G-protein-coupled adenosine receptors (ARs), in particular A

Refugee Stigma And Its Toll On Mental Health: Development And Validation Of The Refugee Stigma Scale (Rss), Hamed Abdollahpour Ranjbar, Khaled Elazab, Ibrahim Yigit, Fatema Almeamari, Ceren Acartürk, Gülşah Kurt, Janet Turan, Andrea Norcini Pala, Bulent Turan

Student Publications [Scholarly]

Background Unprecedented, forced displacement, especially from conflict and war areas, requires addressing resultant mental health issues. Aim Refugees experience mental and physical health problems due to post-displacement stressors, and the pervasive stigma associated with refugee status can exacerbate these difficulties, highlighting the need for a comprehensive assessment tool to understand various facets of refugee stigma. Method We developed the refugee stigma scale (RSS), consisting of 43 items informed by the literature, qualitative and quantitative data. The scale includes four theoretical dimensions of stigma: perceived community stigma, experienced stigma, anticipated stigma and internalised stigma. To examine convergent validity, validated self-report measures …

Preface, Catherine Claire A. Smith

University of Richmond Law Review

No abstract provided.

Foreword, The Honorable Stephen R. Mccullough

University of Richmond Law Review

No abstract provided.

Election Law, Maureen A. Edobor, John J. Martin

University of Richmond Law Review

This is the first year the University of Richmond Law Review has surveyed recent developments in Virginia’s campaign and election laws since 2015. Since then, Virginia’s voting and election statutes have changed significantly, making it one of the most accessible states to vote in, although the campaign finance regulatory framework remains relatively weak. This Article provides a general overview of the state of the law governing (1) campaign finance; (2) voter access and list maintenance; (3) election systems and administration; and (4) redistricting, focusing on significant updates in the past two decades. …

"Creating An Institution": Celebrating The Fortieth Anniversary Of Virginia's Intermediate Appellate Court That Nearly Wasn't, Trevor S. Cox

University of Richmond Law Review

This year marks forty years that the Court of Appeals of Virginia has been in service to the Commonwealth. It is a fitting milestone for celebrating the contributions of the dedicated public servants who have ensured its success. It also is an occasion for recounting how narrowly the court came to be at all. Professor John Douglass touched on that theme in his remarks on the thirtieth anniversary of the court, reminding attendees at a ceremony hosted by the Supreme Court of Virginia, “Today, it is easy to see the necessity for giving birth to the Court of Appeals[,]” but …

Civil Practice And Procedure, Christopher S. Dadak

University of Richmond Law Review

Procedural issues can be seen as dry or hyper technical. Their importance, however, should not be overlooked. The author’s civil procedure professor in law school would consistently share the maxim, paraphrased as: “You can write the substance of the law. I will write the procedure, and I will win every time.” Knowing the proper procedure is often the difference between winning and losing a case. When you lose a case on procedural grounds, it means that your client never got a chance on the actual substance of their case. This article discusses decisions from the Supreme Court of Virginia and …

A Historical Cohort Comparison After Inpatient Admission For Adolescents With Anorexia Nervosa: Feasibility Of Virtual Group Therapy, Elizabeth V Franklin, Margaret Mathias, Rachel Wolfe, Duc T Nguyen, Drusilla M Rosales, Sofia Pedroza, Albert C Hergenroeder, Constance M Wiemann

Center for Medical Ethics and Health Policy Staff Publications

Objective: Access to follow-up care after a medical admission for adolescents with anorexia nervosa (AN) is important; yet access can be delayed or unavailable. This study assessed the feasibility and acceptability of a supplemental virtual 8-week outpatient group therapy program following inpatient care. A secondary aim explored the outpatient program's impact on self-reported anxiety, disordered eating, and depression symptoms, and readmission rates.

Method: A retrospective chart review study compared 68 adolescents (aged 11-18) with AN enrolled in an 8-week group therapy program (Recovery and Prevention Program [RAPP]) to 64 adolescents who were not enrolled in RAPP (historical cohort). "RAPP completers" …

Sensory-Selective Peripheral And Neuraxial Nerve Blockade With 2',6'-Pipecoloxylidide, Claire A Ostertag-Hill, Shuanglong Chen, Tianrui Xue, Rachelle Shao, Matthew Torre, Bin Feng, Zahra Vahedi, Longtu Chen, Steven J Staffa, Yueqin Zheng, Daniel S Kohane

Duncan NRI Faculty and Staff Publications

Background: Safe sensory-selective local anesthetics would be a major advance in the management of acute and chronic pain. This articles describes the sensory-selective local anesthetic properties and the toxicity profile of a known metabolite of amino-amide local anesthetics, 2',6'-pipecoloxylidide (PPX).

Methods: PPX was synthesized and made into its hydrochloride salt. PPX or ropivacaine (ROP) were injected at the sciatic nerve or intrathecally in rats, who then underwent modified hotplate (sensory) testing and weight-bearing (motor) testing. Rats injected with PPX or ROP were assessed for clinical toxicity endpoints. Conduction blockade was studied with single-unit recordings in mice. Biocompatibility was assessed histologically. …

Genome Sequencing Reveals The Impact Of Pseudoexons In Rare Genetic Disease, Georgia Pitsava, Megan Hawley, Light Auriga, Ivan De Dios, Arthur Ko, Sofia Marmolejos, Miguel Almalvez, Ingrid Chen, Kaylee Scozzaro, Jianhua Zhao, Rebekah Barrick, Nicholas Ah Mew, Vincent A Fusaro, Jonathan Lotempio, Matthew Taylor, Luisa Mestroni, Sharon Graw, Dianna Milewicz, Dongchuan Guo, David R Murdock, Kinga M Bujakowska, Changrui Xiao, Emmanuèle C Délot, Seth I Berger, Eric Vilain

Faculty, Staff and Student Publications

Purpose: Advancements in sequencing technologies have significantly improved clinical genetic testing; yet, the diagnostic yield remains around 30% to 40%. Emerging technologies are now being deployed to address the remaining diagnostic gap.

Methods: We tested whether short-read genome sequencing could increase the diagnostic yield in individuals enrolled into the UCI-GREGoR research study, who had suspected Mendelian conditions and prior inconclusive testing. Two other collaborative research cohorts, focused on aortopathy and dilated cardiomyopathy, consisted of individuals who were undiagnosed but had not undergone harmonized prior testing.

Results: We sequenced 353 families (754 participants) and found a molecular diagnosis in 54 (15.3%) …

Restricting Metabolic Plasticity Enhances Stress Adaptation Through The Modulation Of Pdh And Hif1a In Trap1-Depleted Colon Cancer, Hong-Yuan Tsai, Miao-Hsueh Chen, Jihye Yun, Lisa A Lai, John F Valentine, Mary P Bronner, Teresa A Brentnall, Sheng Pan, Ru Chen

Faculty, Staff and Student Publications

Metabolic plasticity allows cancer cells to survive under adverse conditions. To investigate the role of mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) in this process, we used CRISPR/Cas9 mediated genetic deletion to knock out (KO) TRAP1 in colon cancer cells. Depletion of TRAP1 triggered a series of events: induced metabolic reprogramming, increased glycolytic flux, downregulation of mitochondrial complex I, and elevated ROS generation. TRAP1-deficient cells showed tolerance to Oxidative Phosphorylation (OXPHOS) inhibitors and exhibited a higher extracellular acidification rate (ECAR). Additionally, TRAP1 depletion activated hypoxia response elements (HREs) and upregulated HIF1A target genes such as GLUT1 and MCT1. …

Risk Score Roulette: A Cautionary Tale Of Polygenic Risk Score Reliability, Diane Xue, Elizabeth E Blue, Alexis C Wood, Jerome I Rotter, Alison E Fohner

Children’s Nutrition Research Center Staff Publications

Genetic risk prediction for Alzheimer's disease (AD) has high potential impact, yet few studies have assessed the reliability of various polygenic risk score (PRS) methods at the individual level. Here, we evaluated the reliability of AD PRS estimates among 6338 participants from the Multi-Ethnic Study of Atherosclerosis. We compared four PRS models that have been previously associated with dementia risk. Despite similar population-level performance metrics, inter-model reliability of individual-level risk assessment was low, even among individuals classified in the top and bottom deciles. These findings raise serious concerns about the downstream application of PRS for guiding interventions for AD.