Medical Genetics Commons^™

Law Enforcement Use Of Genetic Genealogy Databases In Criminal Investigations: Nomenclature, Definition And Scope, Oliver M Tuazon, Ray A Wickenheiser, Ricky Ansell, Christi J Guerrini, Gerrit-Jan Zwenne, Bart Custers

Center for Medical Ethics and Health Policy Staff Publications

Although law enforcement use of commercial genetic genealogy databases has gained prominence since the arrest of the Golden State Killer in 2018, and it has been used in hundreds of cases in the United States and more recently in Europe and Australia, it does not have a standard nomenclature and scope. We analyzed the more common terms currently being used and propose a common nomenclature: investigative forensic genetic genealogy (iFGG). We define iFGG as the use by law enforcement of genetic genealogy combined with traditional genealogy to generate suspect investigational leads from forensic samples in criminal investigations. We describe iFGG …

Perspectives From Cystinosis: Access To Healthcare May Be A Confounding Factor For Variant Classification, Chen-Han Wilfred Wu, Alicja Tomaszewski, Louisa Stark, Fernando Scaglia, Ewa Elenberg, Fredrick R Schumaker

Faculty, Staff and Students Publications

Genetic variability persists across diverse populations, and it may impact the characterization of heritable diseases in different ancestral groups. Cystinosis is a metabolic disease caused by pathogenic variants in the CTNS gene causing the cellular accumulation of cystine. We attempted to assess the currently poorly characterized prevalence of cystinosis by employing a population genetics methodology. However, we encountered a significant challenge due to genetic variations across different populations, and the consideration of potential disparities in access to healthcare made our results inconclusive. Pathogenic CTNS variants were identified in a representative global population cohort using The Human Gene Mutation Database (HGMD) …

Development Of A Multi-Level/Multi-Modal Intervention For Health Care Transition Preparation, Beth H Garland, Mary Majumder, Constance M Wiemann, Blanca Sanchez-Fournier, Jordyn Babla, Albert C Hergenroeder

Center for Medical Ethics and Health Policy Staff Publications

Aims: Health care transition (HCT) to adult care and young adult disease self-management is a multi-step process involving three major stakeholders - the adolescent, the caregiver, and the provider. Preparation gaps exist within each of these stakeholder groups. This paper presents the development of the Intervention to Promote Autonomy and Competence in Transition-aged Youth (IPACT), a multi-level (adolescent, caregiver, provider), multi-modal (interactive skill building sessions, educational materials, videos) intervention to address gaps in all three stakeholder groups simultaneously and help support achieving the three core elements of HCT planning.

Methods: Eight processes were utilized to develop the IPACT intervention, including …

The Relationship Of Neighborhood Disadvantage, Biological Aging, And Psychosocial Risk And Resilience Factors In Heart Failure Incidence Among Black Persons: A Moderated Mediation Analysis, Ganga S Bey, James R Pike, Anthony S Zannas, Qian Xiao, Bing Yu, Amil M Shah, Priya Palta

Faculty, Staff and Student Publications

Objectives: Deprived living environments contribute to greater heart failure (HF) risk among non-Hispanic Black persons, who disproportionately occupy disadvantaged neighborhoods. The mechanisms for these effects are not fully explicated, partially attributable to an insufficient understanding of the individual factors that contribute additional risk or resilience to the impact of neighborhood disadvantage on health. The objective of this study was, therefore, to clarify the complex pathways over which such exposures act to facilitate more targeted, effective interventions. Given the evidence for a mediating role of biological age and a moderating role of individual psychosocial characteristics in the neighborhood disadvantage-HF link, we …

Benefits Of Sharing Neurophysiology Data From The Brain Initiative Research Opportunities In Humans Consortium, Vasiliki Rahimzadeh, Kathryn Maxson Jones, Mary A Majumder, Michael J Kahana, Ueli Rutishauser, Ziv M Williams, Sydney S Cash, Angelique C Paulk, Jie Zheng, Michael S Beauchamp, Jennifer L Collinger, Nader Pouratian, Amy L Mcguire, Sameer A Sheth

Center for Medical Ethics and Health Policy Staff Publications

Sharing human brain data can yield scientific benefits, but because of various disincentives, only a fraction of these data is currently shared. We profile three successful data-sharing experiences from the NIH BRAIN Initiative Research Opportunities in Humans (ROH) Consortium and demonstrate benefits to data producers and to users.

Genome-Wide Significant Risk Loci For Mood Disorders In The Old Order Amish Founder Population, Elizabeth M Humphries, Kwangmi Ahn, Rachel L Kember, Fabiana L Lopes, Evelina Mocci, Juan M Peralta, John Blangero, David C Glahn, Fernando S Goes, Peter P Zandi, Peter Kochunov, Cristopher Van Hout, Alan R Shuldiner, Toni I Pollin, Braxton D Mitchell, Maja Bucan, L Elliot Hong, Francis J Mcmahon, Seth A Ament

Faculty, Staff and Student Publications

Genome-wide association studies (GWAS) of mood disorders in large case-control cohorts have identified numerous risk loci, yet pathophysiological mechanisms remain elusive, primarily due to the very small effects of common variants. We sought to discover risk variants with larger effects by conducting a genome-wide association study of mood disorders in a founder population, the Old Order Amish (OOA, n = 1,672). Our analysis revealed four genome-wide significant risk loci, all of which were associated with >2-fold relative risk. Quantitative behavioral and neurocognitive assessments (n = 314) revealed effects of risk variants on sub-clinical depressive symptoms and information processing speed. Network …

Big Advocacy, Little Recognition: The Hidden Work Of Black Patients In Precision Medicine, Lynette Hammond Gerido, Kenneth Resnicow, Elena M Stoffel, Tiah Tomlin, Robert Cook-Deegan, Melissa Cline, Amy Coffin, Jill Holdren, Mary Anderlik Majumder, Zhe He

Center for Medical Ethics and Health Policy Staff Publications

As cost-effective next-generation genome sequencing rapidly develops, calls for greater inclusion of Black people in genomic research, policy, and practice are necessary for effective translation of genomic science into precision population health and medicine. Employing a community-based participatory mixed methods research design, we developed a semi-structured survey that was disseminated to three cancer advocacy organizations. Of the 81 survey respondents 49 (60%) self-identified as Black, and 26 (32%) indicated a prior breast cancer diagnosis. Black participants' expressed concerns about genetic testing were evenly distributed between concerns that could be addressed through genetic counseling (24%) and concerns about subsequent use of …

Responding Well To Spiritual Worldviews: A Taxonomy For Clinical Ethicists, Trevor M Bibler

Center for Medical Ethics and Health Policy Staff Publications

Every clinical ethics consultant, no matter their own spirituality, will meet patients, families, and healthcare professionals whose spiritualities anchor their moral worldviews. How might ethicists respond to those who rely on spirituality when making medical decisions? And further, should ethicists incorporate their own spiritual commitments into their clinical analyses and recommendations? These questions prompt reflection on foundational issues in the philosophy of medicine, political and moral theory, and methods of proper clinical ethics consultation. Rather than attempting to offer definitive answers to these questions, this essay prompts readers to consider their own answers to these questions. Specifically, it offers a …

Clinically Indicated Genomic Sequencing Of Children In Foster Care: Legal And Ethical Issues, Hadley Stevens Smith, Emily S Bonkowski, Madison R Hickingbotham, Stacey Pereira, Thomas May, Christi J Guerrini

Center for Medical Ethics and Health Policy Staff Publications

There are approximately 400 000 children in foster care in the US, approximately one-half of whom have chronic health problems and approximately 10% of whom have complex healthcare needs. Given the increasing relevance of genomic sequencing to guide clinical care for children with rare, chronic, and undiagnosed conditions, it may be an important component of diagnostic evaluation for children in foster care. Clinically indicated genomic sequencing may provide information that has health implications for children in foster care, as well as for their biological parents and other relatives. Whether and how genomic sequencing results impact legal decision making and family …

Hope And Optimism In Pediatric Deep Brain Stimulation: Key Stakeholder Perspectives, Natalie Dorfman, Lilly Snellman, Ynez Kerley, Kristin Kostick-Quenet, Gabriel Lazaro-Munoz, Eric A Storch, Jennifer Blumenthal-Barby

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Deep brain stimulation (DBS) is utilized to treat pediatric refractory dystonia and its use in pediatric patients is expected to grow. One important question concerns the impact of hope and unrealistic optimism on decision-making, especially in "last resort" intervention scenarios such as DBS for refractory conditions.

Objective: This study examined stakeholder experiences and perspectives on hope and unrealistic optimism in the context of decision-making about DBS for childhood dystonia and provides insights for clinicians seeking to implement effective communication strategies.

Materials and methods: Semi-structured interviews with clinicians (n = 29) and caregivers (n = 44) were conducted, …

Researching The Future: Scenarios To Explore The Future Of Human Genome Editing, Cynthia Selin, Lauren Lambert, Stephanie Morain, John P Nelson, Dorit Barlevy, Mahmud Farooque, Haley Manley, Christopher T Scott

Center for Medical Ethics and Health Policy Staff Publications

Background: Forward-looking, democratically oriented governance is needed to ensure that human genome editing serves rather than undercuts public values. Scientific, policy, and ethics communities have recognized this necessity but have demonstrated limited understanding of how to fulfill it. The field of bioethics has long attempted to grapple with the unintended consequences of emerging technologies, but too often such foresight has lacked adequate scientific grounding, overemphasized regulation to the exclusion of examining underlying values, and failed to adequately engage the public.

Methods: This research investigates the application of scenario planning, a tool developed in the high-stakes, uncertainty-ridden world of corporate strategy, …

High Foxa1 Levels Induce Er Transcriptional Reprogramming, A Pro-Metastatic Secretome, And Metastasis In Endocrine-Resistant Breast Cancer, Xiaoyong Fu, Resel Pereira, Chia-Chia Liu, Carmine De Angelis, Martin J Shea, Sarmistha Nanda, Lanfang Qin, Tamika Mitchell, Maria L Cataldo, Jamunarani Veeraraghavan, Vidyalakshmi Sethunath, Mario Giuliano, Carolina Gutierrez, Balázs Győrffy, Meghana V Trivedi, Ofir Cohen, Nikhil Wagle, Agostina Nardone, Rinath Jeselsohn, Mothaffar F Rimawi, C Kent Osborne, Rachel Schiff

Center for Medical Ethics and Health Policy Staff Publications

Aberrant activation of the forkhead protein FOXA1 is observed in advanced hormone-related cancers. However, the key mediators of high FOXA1 signaling remain elusive. We demonstrate that ectopic high FOXA1 (H-FOXA1) expression promotes estrogen receptor-positive (ER+) breast cancer (BC) metastasis in a xenograft mouse model. Mechanistically, H-FOXA1 reprograms ER-chromatin binding to elicit a core gene signature (CGS) enriched in ER+ endocrine-resistant (EndoR) cells. We identify Secretome14, a CGS subset encoding ER-dependent cancer secretory proteins, as a strong predictor for poor outcomes of ER+ BC. It is elevated in ER+ metastases vs. primary tumors, irrespective of ESR1 mutations. Genomic ER binding near …

Health Information Seeking In The Digital Age: A National Survey Of Women With Disabilities, Susan Robinson-Whelen, Rosemary B Hughes, Jeanne L Alhusen, Leanne Beers, Charles G Minard, David Davidson

Faculty, Staff and Students Publications

PURPOSE: Access to high quality and accessible online health information (OHI) is critical for reducing disparities, overcoming barriers, and improving the health of women with disabilities. This study aimed to understand women with physical disabilities' use of the Internet to access OHI, most often searched health topics, perceived usefulness of OHI, and self-reported eHealth literacy and challenges in OHI seeking.

METHODS: We conducted a national online survey with 508 women with physical disabilities who used the Internet.

RESULTS: Respondents utilized a wide variety of OHI resources. They searched a broad array of health and disability-related topics, with bowel/bladder and finding …

Intraoperative Predictors Of In-Hospital Mortality After Open Repair Of Ruptured Abdominal Aortic Aneurysms, Nicola Troisi, Giulia Bertagna, Athanasios Saratzis, Simone Guadagni, Fabrizio Minichilli, Daniele Adami, Mauro Ferrari, Raffaella Berchiolli

Center for Medical Ethics and Health Policy Staff Publications

Background: Several models and scores have been released to predict early mortality in patients undergoing surgery for a ruptured abdominal aortic aneurysm (rAAA). These scores included above all preoperative factors and they could be useful to deny surgical repair. The aim of the study was to evaluate intraoperative predictors of in-hospital mortality in patients undergoing open surgical repair (OSR) for a rAAA.

Methods: Between January 2007 and December 2020, 265 patients were admitted at our tertiary referral hospital for a rAAA. Two-hundred-twenty-two patients underwent OSR. Intra-operative factors were analyzed by means of univariate analysis (step 1). Associations of procedure variables …

Evaluating Approaches For Constructing Polygenic Risk Scores For Prostate Cancer In Men Of African And European Ancestry, Burcu F Darst, Jiayi Shen, Ravi K Madduri, Alexis A Rodriguez, Yukai Xiao, Xin Sheng, Edward J Saunders, Tokhir Dadaev, Mark N Brook, Thomas J Hoffmann, Kenneth Muir, Peggy Wan, Loic Le Marchand, Lynne Wilkens, Ying Wang, Johanna Schleutker, Robert J Macinnis, Cezary Cybulski, David E Neal, Børge G Nordestgaard, Sune F Nielsen, Jyotsna Batra, Judith A Clements, Australian Prostate Cancer Bioresource, Henrik Grönberg, Nora Pashayan, Ruth C Travis, Jong Y Park, Demetrius Albanes, Stephanie Weinstein, Lorelei A Mucci, David J Hunter, Kathryn L Penney, Catherine M Tangen, Robert J Hamilton, Marie-Élise Parent, Janet L Stanford, Stella Koutros, Alicja Wolk, Karina D Sørensen, William J Blot, Edward D Yeboah, James E Mensah, Yong-Jie Lu, Daniel J Schaid, Stephen N Thibodeau, Catharine M West, Christiane Maier, Adam S Kibel, Géraldine Cancel-Tassin, Florence Menegaux, Esther M John, Eli Marie Grindedal, Kay-Tee Khaw, Sue A Ingles, Ana Vega, Barry S Rosenstein, Manuel R Teixeira, Nc-La Pcap Investigators, Manolis Kogevinas, Lisa Cannon-Albright, Chad Huff, Luc Multigner, Radka Kaneva, Robin J Leach, Hermann Brenner, Ann W Hsing, Rick A Kittles, Adam B Murphy, Christopher J Logothetis, Susan L Neuhausen, William B Isaacs, Barbara Nemesure, Anselm J Hennis, John Carpten, Hardev Pandha, Kim De Ruyck, Jianfeng Xu, Azad Razack, Soo-Hwang Teo, Canary Pass Investigators, Lisa F Newcomb, Jay H Fowke, Christine Neslund-Dudas, Benjamin A Rybicki, Marija Gamulin, Nawaid Usmani, Frank Claessens, Manuela Gago-Dominguez, Jose Esteban Castelao, Paul A Townsend, Dana C Crawford, Gyorgy Petrovics, Graham Casey, Monique J Roobol, Jennifer F Hu, Sonja I Berndt, Stephen K Van Den Eeden, Douglas F Easton, Stephen J Chanock, Michael B Cook, Fredrik Wiklund, John S Witte, Rosalind A Eeles, Zsofia Kote-Jarai, Stephen Watya, John M Gaziano, Amy C Justice, David V Conti, Christopher A Haiman

Faculty, Staff and Student Publications

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and …

Child And Adolescent Psychiatrists’ Use, Attitudes, And Understanding Of Genetic Testing And Pharmacogenetics In Clinical Practice, Takahiro Soda, Amanda R Merner, Brent J Small, Laura N Torgerson, Katrina Muñoz, Jehannine Austin, Eric A Storch, Stacey Pereira, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

The purpose of this study was to report current practices and attitudes of child and adolescent psychiatrists (CAP) regarding diagnostic genetic and pharmacogenetic (PGx) testing. We surveyed 958 US-based practicing CAP. 54.9% of respondents indicated that they had ordered/referred for a genetic test in the past 12 months. 87% of respondents agreed that it is their role to discuss genetic information regarding psychiatric conditions with their patients; however, 45% rated their knowledge of genetic testing practice guidelines as poor/very poor. The most ordered test was PGx (32.2%), followed by chromosomal microarray (23.0%). 73.4% reported that PGx is at least slightly …

Child And Adolescent Psychiatrists’ Use, Attitudes, And Understanding Of Genetic Testing And Pharmacogenetics In Clinical Practice, Takahiro Soda, Amanda R Merner, Brent J Small, Laura N Torgerson, Katrina Muñoz, Jehannine Austin, Eric A Storch, Stacey Pereira, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

The purpose of this study was to report current practices and attitudes of child and adolescent psychiatrists (CAP) regarding diagnostic genetic and pharmacogenetic (PGx) testing. We surveyed 958 US-based practicing CAP. 54.9% of respondents indicated that they had ordered/referred for a genetic test in the past 12 months. 87% of respondents agreed that it is their role to discuss genetic information regarding psychiatric conditions with their patients; however, 45% rated their knowledge of genetic testing practice guidelines as poor/very poor. The most ordered test was PGx (32.2%), followed by chromosomal microarray (23.0%). 73.4% reported that PGx is at least slightly …

Call For Moral Recognition As Part Of Paediatric Assent, Jared Smith, Jennifer Blumenthal-Barby

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Ethical, Legal, And Social Implications Of Genomics Research: Implications For Building A More Racially Diverse Bioethics Workforce, Faith E Fletcher

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Withdrawing Extra Corporeal Membrane Oxygenation (Ecmo) Against A Family’S Wishes: Three Permissible Scenarios, Trevor M Bibler, Asma Zainab

Center for Medical Ethics and Health Policy Staff Publications

The ethical permissibility of unilaterally withdrawing life-sustaining technologies has been a perennial topic in transplant and critical care medicine, often focusing on CPR and mechanical ventilation. The permissibility of unilateral withdrawal of extracorporeal membrane oxygenation (ECMO) has been discussed sparingly. When addressed, authors have appealed to professional authority rather than substantive ethical analysis. In this Perspective, we argue that there are at least three (3) scenarios wherein healthcare teams would be justified in unilaterally withdrawing ECMO, despite the objections of the patient's legal representative. The ethical considerations that provide the groundwork for these scenarios are, primarily: equity, integrity, and the …

Correction To: Black Bioethics In The Age Of Black Lives Matter, Keisha Ray, Faith E Fletcher, Daphne O Martschenko, Jennifer E James

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Black Bioethics In The Age Of Black Lives Matter, Keisha Ray, Faith E Fletcher, Daphne O Martschenko, Jennifer E James

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Meqtl Mapping In The Genoa Study Reveals Genetic Determinants Of Dna Methylation In African Americans, Lulu Shang, Wei Zhao, Yi Zhe Wang, Zheng Li, Jerome J Choi, Minjung Kho, Thomas H Mosley, Sharon L R Kardia, Jennifer A Smith, Xiang Zhou

Faculty, Staff and Student Publications

Identifying genetic variants that are associated with variation in DNA methylation, an analysis commonly referred to as methylation quantitative trait locus (meQTL) mapping, is an important first step towards understanding the genetic architecture underlying epigenetic variation. Most existing meQTL mapping studies have focused on individuals of European ancestry and are underrepresented in other populations, with a particular absence of large studies in populations with African ancestry. We fill this critical knowledge gap by performing a large-scale cis-meQTL mapping study in 961 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We identify a total of 4,565,687 cis-acting meQTLs …

Refinement Of Saliva Microrna Biomarkers For Sports-Related Concussion, Steven D. Hicks, Cayce Onks, Raymond Y. Kim, Kevin J. Kim, Kevin J. Zhen, Jayson Loeffert, Andrea C. Loeffert, Robert P. Olympia, Gregory Fedorchak, Samantha Devita, Zofia Gagnon, Callan Mcloughlin, Miguel M. Madeira, Scott L. Zuckerman, Timothy Lee, Matthew Heller, Chuck Monteith, Thomas R. Campbell, Christopher Neville, Elise Fengler, Michael N. Dretsch

Rehabilitation Sciences Faculty Publications

Purpose

Recognizing sport-related concussion (SRC) is challenging and relies heavily on subjective symptom reports. An objective, biological marker could improve recognition and understanding of SRC. There is emerging evidence that salivary micro-ribonucleic acids (miRNAs) may serve as biomarkers of concussion; however, it remains unclear whether concussion-related miRNAs are impacted by exercise. We sought to determine whether 40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports. Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise.

Methods

This case-control study harmonized …

Comparison Of Neurocognitive And Quality-Of-Life Outcomes In Pediatric Craniopharyngioma Patients Treated With Partial Resection And Radiotherapy Versus Gross-Total Resection Only, Guillermo Aldave, M Fatih Okcu, Murali Chintagumpala, Lucia Ruggieri, Charles G Minard, Fatema Malbari, Lisa E Mash, Arnold C Paulino, Susan Mcgovern, Uma Ramaswamy, William Whitehead, Lisa S Kahalley

Faculty, Staff and Students Publications

OBJECTIVE: The optimal management of pediatric craniopharyngioma patients remains controversial, shifting from radical resection (gross-total resection [GTR]) to a more conservative approach with partial resection/biopsy followed by radiotherapy (PR+RT). To the authors' knowledge, no previous studies have compared neurocognitive and quality-of-life (QOL) outcomes between the two main treatments. In this study, the authors compared changes in intellectual, adaptive, and QOL scores in children treated for craniopharyngioma with GTR and those treated with PR+RT.

METHODS: Patients underwent annual neurocognitive and QOL evaluations for up to 10 years posttreatment, including the Full-Scale IQ, Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working …

Ethical Hazards Of Health Data Governance In The Metaverse, Kristin Kostick-Quenet, Vasiliki Rahimzadeh

Center for Medical Ethics and Health Policy Staff Publications

Metaverse-enabled healthcare is no longer hypothetical. Developers must now contend with ethical, legal and social hazards if they are to overcome the systematic inefficiencies and inequities that exist for patients who seek care in the real world.

Framing The Family: A Qualitative Exploration Of Factors That Shape Family-Level Experience Of Pediatric Genomic Sequencing, Hadley Stevens Smith, Emily S Bonkowski, Madison R Hickingbotham, Raymond Belanger Deloge, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Families of children with rare and undiagnosed conditions face many psychosocial and logistical challenges that may affect their approach to decisions about their child’s care and their family’s well-being. As genomic sequencing (GS) is increasingly incorporated into pediatric diagnostic workups, assessing the family-level characteristics that shape the experience of pediatric GS is crucial to understanding how families approach decision-making about the test and how they incorporate the results into their family life. We conducted semi-structured interviews with parents and other primary caregivers of pediatric patients who were evaluated for a suspected genetic condition and who were recommended to have GS …

Antagonistic Pleiotropy In Alzheimer's Disease, Annie Hollis

Undergraduate Research Conference

Apolipoprotein E (APOE) ε4 allele has been linked with Alzheimer’s disease; specifically having two copies of the APOE ε4 allele greatly increases the risk of developing Alzheimer’s disease in older age. Studies have attempted to relate an antagonistic pleiotropy hypothesis to this gene, i.e., the ε4 allele has positive effects on cognition and memory in early life and negative effects later in life. Many of these studies have had several limitations and conflicting results, such as testing adults in upper middle age or comparing the absence of the ε4 allele with the presence of at least one ε4 allele. Studies …

Interaction Analysis Of Ancestry-Enriched Variants With Apoe-Ɛ4 On Mci In The Study Of Latinos-Investigation Of Neurocognitive Aging, Einat Granot-Hershkovitz, Rui Xia, Yunju Yang, Brian Spitzer, Wassim Tarraf, Priscilla M Vásquez, Richard B Lipton, Martha Daviglus, Maria Argos, Jianwen Cai, Robert Kaplan, Myriam Fornage, Charles Decarli, Hector M Gonzalez, Tamar Sofer

Faculty, Staff and Student Publications

APOE-ɛ4 risk on Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) differs between race/ethnic groups, presumably due to ancestral genomic background surrounding the APOE locus. We studied whether African and Amerindian ancestry-enriched genetic variants in the APOE region modify the effect of the APOE-ɛ4 alleles on Mild Cognitive Impairment (MCI) in Hispanics/Latinos. We defined African and Amerindian ancestry-enriched variants as those common in one Hispanic/Latino parental ancestry and rare in the other two. We identified such variants in the APOE region with a predicted moderate impact based on the SnpEff tool. We tested their interaction with APOE-ɛ4 on MCI in …

Hervs And Cancer-A Comprehensive Review Of The Relationship Of Human Endogenous Retroviruses And Human Cancers, Erik Stricker, Erin C Peckham-Gregory, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

Genomic instability and genetic mutations can lead to exhibition of several cancer hallmarks in affected cells such as sustained proliferative signaling, evasion of growth suppression, activated invasion, deregulation of cellular energetics, and avoidance of immune destruction. Similar biological changes have been observed to be a result of pathogenic viruses and, in some cases, have been linked to virus-induced cancers. Human endogenous retroviruses (HERVs), once external pathogens, now occupy more than 8% of the human genome, representing the merge of genomic and external factors. In this review, we outline all reported effects of HERVs on cancer development and discuss the HERV …