Bioethics and Medical Ethics Commons^™

Advancing Medical Applications Of Cancer Nanotechnology: Highlighting Two Decades Of The Nci's Nanotechnology Characterization Laboratory Service To The Research Community, Rachael M Crist, Yechezkel Barenholz, Ahuva Cern, Kate N Clark, Pieter R Cullis, Cheryl Dean, Neil Desai, Mauro Ferrari, Matthieu Germain, Carmen A Giacomantonio, Emma Grabarnik, Piotr Grodzinski, Atara Hod, Barry E Kennedy, Ruvanthi N Kularatne, Glen S Kwon, Emmanuel Loeb, Erin B Noftall, Len Pagliaro, Morteza Rasoulianboroujeni, Alexander Roth, Darren Rowles, Kulbir Singh, Nicole F Steinmetz, Zhanna Yehtina, Yao Zhang, Daniel Zilbersheid, Jeffrey D Clogston, Stephan T Stern, Marina A Dobrovolskaia

Center for Medical Ethics and Health Policy Staff Publications

The Nanotechnology Characterization Laboratory (NCL) is a US federally funded resource providing characterization and expertise to the cancer nanomedicine research community. Founded as a formal partnership among the US National Cancer Institute (NCI), the US Food and Drug Administration (FDA), and the US National Institute of Standards and Technology (NIST), the NCL has spent two decades developing a one-of-a-kind service with broad multidisciplinary expertise to meet the needs of a rapidly evolving drug development field. To mark the 20th anniversary of the lab's founding, the NCL hosted a symposium to highlight the achievements of the cancer nanomedicine field, showcase novel, …

Methadone For Critically Ill Patients Under Mechanical Ventilation In The Intensive Care Unit: A Systematic Review, Sérgio Martins Pereira, Megan Abbott, João Francisco Figueiredo Marcondes Ferraz, Akash Goel, Andrea Rigamonti, Charmaine De Castro, Lisa Burry, Airton Leonardo De Oliveira Manoel, Michael Chaim Sklar

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Pain may pose significant challenges in the intensive care unit, especially in mechanically ventilated patients. Methadone has recently emerged as an alternative option for eliciting acute analgesia. In this systematic review, we evaluated the use of methadone in mechanically ventilated patients in the intensive care unit.

Source: We searched MEDLINE, EMBASE, Wiley's Cochrane Library, CINAHL, PubMed (non-MEDLINE), Scopus, and LILACS databases from inception to January 24th, 2025. Eligible studies included randomized controlled trials and observational studies that compared the use of methadone to the standard of care or to other analgosedation strategies in mechanically ventilated patients in the intensive …

Investigative Genetic Genealogy Practices Warranting Policy Attention: Results Of A Modified Policy Delphi, Christi J Guerrini, Louiza Kalokairinou, Jill O Robinson, Whitney Bash Brooks, Stephanie M Fullerton, Sara Huston, Jacklyn Dahlquist, Diana Madden, Norah Crossnohere, Nicola Campoamor, John F P Bridges, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

A technique known as investigative genetic genealogy (IGG) was first introduced to criminal investigations in 2018, and it has since been used by U.S. law enforcement to help identify hundreds of criminal perpetrators and unidentified human remains. As expertise in IGG grows, policymakers have shown interest in regulating it. To help inform these efforts and to promote coherence in IGG governance as it expands, we recruited experts representing a spectrum of IGG-relevant professions and perspectives to identify and prioritize IGG practices for policy attention and to develop policy options for addressing them. In two rounds of a modified policy Delphi, …

Survivorship From Pediatric And Adult Brain Tumors: The 2024 Brain Tumor Epidemiology Consortium Meeting Report, Scott L Coven, Roberta Mckean-Cowdin, Michael E Scheurer, Kimberly J Johnson, Luc Bauchet, Carol Kruchko, Ching C Lau, Quinn T Ostrom, John Villano, Yan Yuan, Friederike Erdmann

Center for Medical Ethics and Health Policy Staff Publications

The Brain Tumor Epidemiology Consortium (BTEC) is an international organization with membership of individuals from the scientific community with interests related to brain tumor epidemiology, including surveillance, classification, methodology, etiology, and factors associated with morbidity and survival. The 2024 annual BTEC meeting entitled “Survivorship from Pediatric and Adult Brain Tumors” was held in Mainz, Germany, USA, on May 15–17, 2024. The meeting gathered scientists from Africa, Australia, Europe, and North America and included 4 keynote sessions focusing on brain tumor survivorship across the age spectrum. The meeting included 3 abstract sessions, which also included scientific talks around brain …

Reframing Stigma In Tourette Syndrome: An Updated Scoping Review, Kelly Pring, Melina Malli, Brandy W Hardy, Stephen R Rapp, Eric A Storch, Jonathan W Mink, Jaclyn M Martindale

Center for Medical Ethics and Health Policy Staff Publications

Persistent tic disorders (PTD) such as Tourette's syndrome (TS) are common childhood-onset neurodevelopmental disorders. Stigmatization of individuals with these disorders remains an ongoing problem. The purpose of this scoping review is to serve as an updated review of the research regarding stigmatization in youth with PTD since the publication of the original systematic review about this topic in 2016. The electronic databases Embase, Web of Science, PubMed, PsycINFO, and CINAHL were searched. Of the 4751 initial articles screened after removing duplications, 47 studies met the inclusion criteria. The studies were examined under the social-ecological stigmatization model, which helps categorize stigmatization …

Talking About Suffering In The Intensive Care Unit, Brent M Kious, Judith B Vick, Peter A Ubel, Olivia Sutton, Jennifer Blumenthal-Barby, Christopher E Cox, Deepshikha Ashana

Center for Medical Ethics and Health Policy Staff Publications

Background: Some have hypothesized that talk about suffering can be used by clinicians to motivate difficult decisions, especially to argue for reducing treatment at the end of life. We examined how talk about suffering is related to decision-making for critically ill patients, by evaluating transcripts of conversations between clinicians and patients' families.

Methods: We conducted a secondary qualitative content analysis of audio-recorded family meetings from a multicenter trial conducted in the adult intensive care units of five hospitals from 2012-2017 to look at how the term "suffering" and its variants were used. A coding guide was developed by consensus-oriented discussion …

Patient-Centric Federated Learning: Automating Meaningful Consent To Health Data Sharing With Smart Contracts, Kristin M Kostick-Quenet, Marcelo Corrales Compagnucci, Mateo Aboy, Timo Minssen

Center for Medical Ethics and Health Policy Staff Publications

Federated Learning (FL) promises to enhance data-driven health research by enabling collaborative machine learning across distributed datasets without direct data exchange. However, current FL implementations primarily reflect the data-sharing interests of institutional controllers rather than those of individual patients whose data are at stake. Existing consent mechanisms-like broad consent under HIPAA or explicit consent under the GDPR-fail to provide patients with control over how their data is used. This article explores the integration of smart contracts (SCs) into FL as a mechanism for automating, enforcing, and documenting consent in data transactions. SCs, encoded in decentralized ledger technologies, can ensure that …

Deep Brain Stimulation For Childhood Treatment-Resistant Obsessive-Compulsive Disorder: Mental Health Clinician Views On Candidacy Factors, Ilona Cenolli, Tiffany A Campbell, Natalie Dorfman, Meghan Hurley, Jared N Smith, Kristin Kostick-Quenet, Eric A Storch, Jennifer Blumenthal-Barby, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Deep brain stimulation (DBS) is approved under a humanitarian device exemption to manage treatment-resistant obsessive-compulsive disorder (TR-OCD) in adults. It is possible that DBS may be trialed or used clinically off-label in children and adolescents with TR-OCD in the future. DBS is already used to manage treatment-resistant childhood dystonia. Evidence suggests it is a safe and effective intervention for certain types of dystonia. Important questions remain unanswered about the use of DBS in children and adolescents with TR-OCD, including whether mental health clinicians would refer pediatric patients for DBS, and who would be a good candidate for DBS.

Objectives: …

Investigation Of The Relationship Between Nursing Students’ Ethical Sensitivities And Care Behaviors, Pınar Yel, Neriman Zengin, Aysenur Çetin Üçeriz

Makara Journal of Health Research

Background: Care encompassing ethical and legal aspects is essential for nursing and involves actions that aim to improve individual well-being. In this study, we assessed the relationship between nursing students’ ethical sensitivity and care behaviors.

Methods: This descriptive study included 191 students enrolled at a foundation university who consented to participate. Relevant data were gathered by using the Descriptive Information Form, Ethical Sensitivity Scale Adapted for Nursing Students, and Caring Behaviors Scale-24. Surveys were conducted face-to-face with the attending students and via Google Forms for the non-attending students.

Results: The mean total score of the ethical sensitivity …

Challenges To Reproductive Justice: An Ethical Analysis Of Reproductive Technologies And Disparities, Courtney Brenner

Electronic Theses and Dissertations

This dissertation analyzes the Reproductive Justice Framework to describe possible solutions to the ethical challenges related to reproductive healthcare disparities. Various frameworks to support reproductive equity fail to address the challenges marginalized individuals face in accessing reproductive health services. The four ethical principles of autonomy, beneficence, nonmaleficence, and justice serve as foundational tools to support reducing these disparities. This dissertation uses the Reproductive Justice Framework to analyze the unequal distribution of harms among marginalized women. It highlights how access to care, such as Assisted Reproductive Technologies (ART), is disproportionately inaccessible to marginalized women. Then, it discusses the relationship between marginalized …

Ethical Considerations In The Diagnosis And Treatment Of Autism Spectrum Disorder, Ferdinand Okafor

Electronic Theses and Dissertations

This dissertation is an ethical response to the ethical issues in the assessment, diagnosis, and treatment of autism. The problems that underlie the discussion are misconception about autism and Autistics. The misconception about autism and Autistics lead to misinterpretation of the neurological functioning, cognition, and the behaviors of Autistics. Consequently, it influences the approach and model of care in the assessment, diagnosis, and treatment of autism. Currently, the analytic approach and biomedical model of disease are applied in the assessment, diagnosis, and treatment of autism. The motive of the analytic approach and biomedical care is to cure autism. The consequence …

Muslim Spirituality As A Foundation In Bioethics For Patient Encounters In Health Care, Sara Rahman

Electronic Theses and Dissertations

Spirituality plays a major role in decision making for individuals with faith-based values. There is often hesitation to discuss the role of faith in healthcare as a core value and coping mechanism. The growing cultural diversity amongst patients and physicians has increased the need to understand eastern religious principles and incorporate them into bioethical guidance. Even as the 2nd largest religion in the world, Islam has not been sufficiently integrated into religious bioethics in western medicine. Muslim populations of patients and physicians are growing, increasing the need for better understanding of how Islamic principles impact healthcare delivery. Although Islamic law …

The Ethical Contributions Of Nudges To Healthcare, Ian Doherty

Electronic Theses and Dissertations

“The Ethical Contributions of Nudges to Healthcare” examines the ethical use, implications, and rationale for using nudges in healthcare. The use of nudges in healthcare are being empirically examined. This leaves much to be examined from the ethical perspective. To examine the ethical perspective, the dissertation lays out how nudges interact with and enhance the biomedical principles of autonomy and beneficence. The dissertation then turns to clinical ethics. Nudges, more specifically the framing effect, are paired with trust in the patient-physician relationship to discern how best to aid a patient in his or her medical decision-making. The dissertation then investigates …

The Ethics Of Involuntary Psychiatric Hospitalization: A Comprehensive Analysis Of Policies, Practice, And Ethical Oversight, Mariah Chobany

Electronic Theses and Dissertations

As a specialized field of medicine, psychiatry presents unique ethical challenges and dilemmas distinct from other medical disciplines. A particularly complex aspect of psychiatric care involves the involuntary treatment of patients who may be unable to make informed decisions about their care or participation in research due to the debilitating effects of their psychiatric condition. This presents a significant challenge for providers and researchers, particularly concerning capacity issues and the informed consent process. Despite the intricacies and complexities of ethical dilemmas in psychiatric treatment and research, there is a notable lack of comprehensive guidance in policies and practices on addressing …

From Policymaking To Legislation, The Need For A Secular Turn In Bioethics Discourse To Uphold, As A Function Of The Greater Good, Policy For Legislation Of Medically Aided Dying In The United States Of America, Scott Dyer

Electronic Theses and Dissertations

A person’s right to self-determination is a central aspect of living in a democratic nation. Similarly, decisions regarding medical care are generally left up to the patient to determine what treatment is or is not appropriate. The same should apply to end-of-life care as well, especially when a patient desires to hasten his or her death via medically aided dying. However, due to the illegality of medically assisted dying in most of the United States, the right to a self-determined death is not possible for the majority of American citizens. One of the main reasons for this is due to …

Learning To Be An Autistic Therapist: Personal Steps Towards An Autism-Affirming Psychotherapy, Sasha D. Strong

Ought: The Journal of Autistic Culture

How can Autistic therapists understand and support themselves, and how can this help them support their clients? In this paper, I recount my personal journey of healing and growth as an Autistic psychotherapist, 16 months after self-identification. Here is an overview of conceptual frameworks from #actuallyautistic authors, critical theory, queer theory, and social justice that I have found helpful. I also share some of the therapeutic and wellness approaches that have been important to me, including mindfulness and bodyfulness. Organic knowing has been pivotal for me in discerning between masking and aliveness, and regaining a choice around masking behaviors. This …

Health Equity Innovation In Precision Medicine: Data Stewardship And Agency To Expand Representation In Clinicogenomics, Patrick J Silva, Vasiliki Rahimzadeh, Reid Powell, Junaid Husain, Scott Grossman, Adam Hansen, Jennifer Hinkel, Rafael Rosengarten, Marcia G Ory, Kenneth S Ramos

Center for Medical Ethics and Health Policy Staff Publications

Most forms of clinical research examine a very minute cross section of the patient journey. Much of the knowledge and evidence base driving current genomic medicine practice entails blind spots arising from underrepresentation and lack of research participation in clinicogenomic databases. The flaws are perpetuated in AI models and clinical practice guidelines that reflect the lack of diversity in data being used. Participation in clinical research and biobanks is impeded in many populations due to a variety of factors that include knowledge, trust, healthcare access, administrative barriers, and technology gaps. A recent symposium brought industry, clinical, and research participants in …

The Living Document, Camilla Lyckblad

Proceedings from the Document Academy

This physical interactive art piece of thesis research in progress aims to deepen comprehension of information behavior in clinical contexts, where the contemporary medical record, with its increasing digital properties such as open record access for patients, can be viewed as an entity that both listens and influences. The art piece sheds light on the complex dynamics of truth within clinical environments, where patients and healthcare professionals might selectively disclose or withhold information, aiming to protect both patient, clinician and the information itself. Set within a small, dimly lit room, the exhibit features eight aged medical records, each inscribed with …

The Living Document: Medical Records As A Malleable Presence, Camilla Lyckblad

Proceedings from the Document Academy

Understanding why individuals might safeguard information or keep secrets in working documents such as medical records is essential for the development of good quality care, fostering an environment where both patients and staff feel secure to part with sensitive information, encouraging more honest and open communication as well as improved quality of care. This ongoing research aims to deepen comprehension of information behavior in clinical contexts, where the contemporary medical record, with its increasing properties such as open record access for patients, can be viewed as an entity that both listens and influences. This examination sheds light on the complex …

Food Security And Its Impact On Hypertension In Urban Communities, Lauren M. Nobriga

Master's Projects and Capstones

The Quality Improvement Team proposed an intervention to increase enrollment in the Food Security Program, a six-month initiative that provides vouchers redeemable for fruits and vegetables. Long-term impacts of this Program include an improved food economy and enhanced patient disease management autonomy. This project aimed to increase the percentage of eligible adult medicine clinic patients enrolled in the Food Security Program by 25%, or 11 patients per month, based on the mean enrollment for the first four months of the Program (May to August) of nine patients. The intervention was based on bi-monthly performance reports, making the goal include enrolling …

What Patients And Caregivers Want To Know When Consenting To The Use Of Digital Behavioral Markers, Anika Sonig, Christine Deeney, Meghan E Hurley, Eric A Storch, John Herrington, Gabriel Lázaro-Muñoz, Casey J Zampella, Birkan Tunc, Julia Parish-Morris, Jenny Blumenthal-Barby, Kristin Kostick-Quenet

Center for Medical Ethics and Health Policy Staff Publications

Artificial intelligence (AI)-based computational tools for deriving digital behavioral markers are increasingly able to automatically detect clinically relevant patterns in mood and behavior through algorithmic analysis of continuously and passively collected data. The integration of these technologies into clinical care is imminent, most notably in clinical psychology and psychiatry but also other disciplines (e.g., cardiology, neurology, neurosurgery, pain management). Meanwhile, ethical guidelines for implementation are lacking, as are insights into what patients and caregivers want and need to know about these technologies to ensure acceptability and informed consent. In this work, we present qualitative findings from interviews with 40 adolescent …

The Challenge Of Regulating Pharmaceutical Clinical Trials In The 21st Century With A Focus On Guatemala, Alejandro Cerón, Antonio Ricafort, Carter Saccocio, Maria Delmonte, Jordan Vasquez, Amarri Bishop, Julia Atwood, Addison Bucsko, Jordan Lewis, Alexandra Welch, Itzael Garcia, Ella Wald, Selena Johnson, Crystal Jin, Talya Riciputi, Lindsey Speer, Vanessa Udo-Obong, Soren Engberg, Tessa Lindstrom

Anthropology: Undergraduate Student Scholarship

This report was prepared by the students and instructor of the "Right to Health in Theory and Practice" class taught in the fall of 2024 at the University of Denver. The report was prepared for the Vice Ministry of Health Regulation, Surveillance and Control of the Ministry of Public Health and Social Assistance of Guatemala. The work used the following guiding question: What can a country like Guatemala do to regulate international pharmaceutical clinical trials in the context of research commercialization? In other words, the work was guided by three important elements. First, the regulatory aspect of clinical trials. Second, …

Inflammation Mediated By Gut Microbiome Alterations Promotes Lung Cancer Development And An Immunosuppressed Tumor Microenvironment, Zahraa Rahal, Yuejiang Liu, Fuduan Peng, Sujuan Yang, Mohamed A Jamal, Manvi Sharma, Hannah Moreno, Ashish V Damania, Matthew C Wong, Matthew C Ross, Ansam Sinjab, Tieling Zhou, Minyue Chen, Inti Tarifa Reischle, Jiping Feng, Chidera Chukwuocha, Elizabeth Tang, Camille Abaya, Jamie K Lim, Cheuk Hong Leung, Heather Y Lin, Nathaniel Deboever, Jack J Lee, Boris Sepesi, Don L Gibbons, Jennifer A Wargo, Junya Fujimoto, Linghua Wang, Joseph F Petrosino, Nadim J Ajami, Robert R Jenq, Seyed Javad Moghaddam, Tina Cascone, Kristi Hoffman, Humam Kadara

Center for Medical Ethics and Health Policy Staff Publications

Accumulating evidence indicates that the gut microbiome influences cancer progression and therapy. We recently showed that progressive changes in gut microbial diversity and composition are closely coupled with tobacco-associated lung adenocarcinoma in a human-relevant mouse model. Furthermore, we demonstrated that the loss of the antimicrobial protein Lcn2 in these mice exacerbates protumor inflammatory phenotypes while further reducing microbial diversity. Yet, how gut microbiome alterations impinge on lung adenocarcinoma development remains poorly understood. In this study, we investigated the role of gut microbiome changes in lung adenocarcinoma development using fecal microbiota transfer and delineated a pathway by which gut microbiome alterations …

Excess Mortality In Persons With Concurrent Hiv And Cancer Diagnoses: A Retrospective Cohort Study, Kamaria L Lee, Varada Sarovar, Jennifer O Lam, Wendy A Leyden, Stacey E Alexeeff, Alexandra N Lea, Rulin C Hechter, Haihong Hu, Julia L Marcus, Qing Yuan, Jennifer R Kramer, Lilie L Lin, Elizabeth Y Chiao, William J Towner, Michael A Horberg, Michael J Silverberg

Center for Medical Ethics and Health Policy Staff Publications

Background: With extended lifespans for people with human immunodeficiency virus (PWH), there is a corresponding increased burden of chronic illnesses, including cancer. Our objective was to estimate the excess mortality among PWH with cancer compared with people without HIV (PWoH), accounting for the higher background mortality in the general PWH population.

Methods: We identified 39,000 PWH and 387,767 demographically matched PWoH in three integrated healthcare systems from 2000 to 2016. We estimated excess mortality among PWH with cancer, computed as the cancer mortality rate difference-in-difference comparing PWH and PWoH. We evaluated five cancer groups: any cancer; virus-, human papillomavirus-, and …

Citation Bias, Diversity, And Ethics, Keisha S Ray, Perry Zurn, Jordan D Dworkin, Dani S Bassett, David B Resnik

Faculty and Staff Publications

How often a researcher is cited usually plays a decisive role in that person's career advancement, because academic institutions often use citation metrics, either explicitly or implicitly, to estimate research impact and productivity. Research has shown, however, that citation patterns and practices are affected by various biases, including the prestige of the authors being cited and their gender, race, and nationality, whether self-attested or perceived. Some commentators have proposed that researchers can address biases related to social identity or position by including a Citation Diversity Statement in a manuscript submitted for publication. A Citation Diversity Statement is a paragraph placed …

Metagenomic Sequencing For Early Detection Of Future Engineered Pandemics: Foreshadowing The Privacy Challenge, Nir Eyal, Bridget Williams, Kevin M. Esvelt, Jane R. Bambauer

UF Law Faculty Publications

In this commentary, we imagine how a global system of metagenomic sequencing could be governed in order to reap the benefits and manage the risks. Global institutional engineers and their academic partners would need to develop a new governance model to ensure that all partners involved in a global metagenomic surveillance system cooperate as needed.

Addressing Ethical Issues In Healthcare Artificial Intelligence Using A Lifecycle-Informed Process, Benjamin X Collins, Jean-Christophe Bélisle-Pipon, Barbara J Evans, Kadija Ferryman, Xiaoqian Jiang, Camille Nebeker, Laurie Novak, Kirk Roberts, Martin Were, Zhijun Yin, Vardit Ravitsky, Joseph Coco, Rachele Hendricks-Sturrup, Ishan Williams, Ellen W Clayton, Bradley A Malin, Bridge2ai Ethics And Trustworthy Ai Working Group

Faculty, Staff and Student Publications

OBJECTIVES: Artificial intelligence (AI) proceeds through an iterative and evaluative process of development, use, and refinement which may be characterized as a lifecycle. Within this context, stakeholders can vary in their interests and perceptions of the ethical issues associated with this rapidly evolving technology in ways that can fail to identify and avert adverse outcomes. Identifying issues throughout the AI lifecycle in a systematic manner can facilitate better-informed ethical deliberation.

MATERIALS AND METHODS: We analyzed existing lifecycles from within the current literature for ethical issues of AI in healthcare to identify themes, which we relied upon to create a lifecycle …

The Ethics Of Vulnerability In Health Care, Hannah Dieterle

Electronic Theses and Dissertations

This dissertation seeks to address vulnerability within clinical healthcare settings. Currently, clinical vulnerability is underrecognized and insufficiently researched which leads to the perpetuation of negative health outcomes for vulnerable populations. Specifically, there is a lack of a consistent and universal definition of vulnerability which has built a shaky foundation on which to discuss vulnerability. This dissertation begins to address these issues and increase awareness on clinical vulnerability due to some populations experiencing the devastating effects of vulnerability at a higher and disproportionate rate when compared to other populations. There is a clear need for increased attention from ethicists and medical …

Implementing And Assessing Climate Change Education In A Pediatrics Residency Curriculum, Mark Mcshane, Shelley Kumar, Linessa Zuniga

Center for Medical Ethics and Health Policy Staff Publications

Background For physicians to effectively combat the growing health crisis that is climate change, they should begin learning during medical training about its health implications. However, there is little data on residents' knowledge of the climate crisis, and even less data regarding the effectiveness and acceptability of climate change education in graduate medical training programs. Objective To incorporate a new educational session on the health implications of climate change into a residency curriculum and evaluate the acceptability of the session and its effects on residents' knowledge, attitudes, and perceptions of the topic.

Methods In July 2021, a 90-minute, interactive, small-group …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

Methods: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

Results: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10-8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p = 1.9 × 10-9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p = 7.2 × 10-8).

Discussion: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

Highlights: We determine the association of genetic variants with Alzheimer's disease (AD) using …