Characterizing epigenetic aging in an adult sickle cell disease cohort.

Abstract

Abstract

Sickle cell disease (SCD) affects ∼100 000 predominantly African American individuals in the United States, causing significant cellular damage, increased disease complications, and premature death. However, the contribution of epigenetic factors to SCD pathophysiology remains relatively unexplored. DNA methylation (DNAm), a primary epigenetic mechanism for regulating gene expression in response to the environment, is an important driver of normal cellular aging. Several DNAm epigenetic clocks have been developed to serve as a proxy for cellular aging. We calculated the epigenetic ages of 89 adults with SCD (mean age, 30.64 years; 60.64% female) using 5 published epigenetic clocks: Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE. We hypothesized that in chronic disease, such as SCD, individuals would demonstrate epigenetic age acceleration, but the results differed depending on the clock used. Recently developed clocks more consistently demonstrated acceleration (GrimAge, DunedinPACE). Additional demographic and clinical phenotypes were analyzed to explore their association with epigenetic age estimates. Chronological age was significantly correlated with epigenetic age in all clocks (Horvath, r = 0.88; Hannum, r = 0.89; PhenoAge, r = 0.85; GrimAge, r = 0.88; DunedinPACE, r = 0.34). The SCD genotype was associated with 2 clocks (PhenoAge, P = .02; DunedinPACE, P < .001). Genetic ancestry, biological sex, β-globin haplotypes, BCL11A rs11886868, and SCD severity were not associated. These findings, among the first to interrogate epigenetic aging in adults with SCD, demonstrate epigenetic age acceleration with recently developed epigenetic clocks but not older-generation clocks. Further development of epigenetic clocks may improve their predictive ability and utility for chronic diseases such as SCD.

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Citation

Published Version (Please cite this version)

10.1182/bloodadvances.2023011188

Publication Info

Lê, Brandon M, Daniel Hatch, Qing Yang, Nirmish Shah, Faith S Luyster, Melanie E Garrett, Paula Tanabe, Allison E Ashley-Koch, et al. (2024). Characterizing epigenetic aging in an adult sickle cell disease cohort. Blood advances, 8(1). pp. 47–55. 10.1182/bloodadvances.2023011188 Retrieved from https://hdl.handle.net/10161/30065.

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Scholars@Duke

Yang

Qing Yang

Associate Research Professor in the School of Nursing

Dr. Qing Yang is Associate Professor and Biostatistician at Duke School of Nursing. She received her PhD in Biostatistics from University of California, Los Angeles. Dr. Yang’s statistical expertise is longitudinal data analysis and time-to-event data analysis. As a biostatistician, she has extensive experience collaborating with researchers in different therapeutic areas, including diabetes, cancer, cardiovascular disease and mental health. Her current research interests are advanced latent variable models that are widely used in symptom cluster research and intensive longitudinal data analysis that arise from mobile health research.

Shah

Nirmish Ramesh Shah

Associate Professor of Medicine
Tanabe

Paula J Tanabe

Laurel Chadwick Distinguished Professor of Nursing

Dr. Tanabe is the Laurel B. Chadwick Distinguished Professor in the Schools of Nursing and Medicine at Duke at the Duke University School of Nursing. Dr. Tanabe is a clinical and health services researcher. Her program of research focuses on improving systems of healthcare and patient outcomes for persons with sickle cell disease, a primarily minority and under-served population. Dr. Tanabe has received funding from the Agency for Health Care Research and Quality, the National Institute of Heart, Lung, and Blood, National Institute of Minority Health and Health Disparities and the National Institute of Nursing Research. Her work is advancing the care of individuals with sickle cell disease with a strong focus on improving pain management in the emergency department during a vaso-occlusive crisis. Her methodological expertise includes conducting multi-site clinical RCT’s, survey methods, qualitative research, quality improvement and implementation science. Dr. Tanabe has a strong passion for her work, individuals with sickle cell disease, and for mentoring students and faculty to conduct important, meaningful work to improve the health and well being of individuals and families.

Ashley-Koch

Allison Elizabeth Ashley-Koch

Professor in Medicine

My work focuses on the dissection of human traits using multi-omic technologies (genetics, epigenetics, metabolomics and proteomics).  I am investigating the basis of several neurological and psychiatric conditions such as neural tube defects and post-traumatic stress disorder. I also study modifiers of sickle cell disease.

Knisely

Mitchell Knisely

Associate Professor in the School of Nursing

Dr. Mitchell Knisely, PhD, RN, ACNS-BC, PMGT-BC, FAAN is an Associate Professor in the Healthcare in Adult Populations Division of the Duke University School of Nursing.

Dr. Knisely’s research focuses on the application of precision health approaches to understand and ameliorate pain and promote equitable pain care in individuals with sickle cell disease and other chronic pain conditions. His program of research includes studies seeking to understand biopsychosocial contributors to individuals' pain experiences, as well as pragmatic clinical trials evaluating the use of non-pharmacological interventions (e.g., acupuncture) for the treatment of acute and chronic pain.

Dr. Knisely is board certified as an Adult Health Clinical Nurse Specialist and in Pain Management Nursing. He earned his BSN from Purdue University and his MSN and PhD from Indiana University. He completed a postdoctoral fellowship in genomics at the University of Pittsburgh School of Nursing and trained at NIH's National Institute of Nursing Research Summer Genetics Institute. His research and training have been supported by several internal and external grants, including funding from the National Institutes of Health. Dr. Knisely is a Fellow in the Betty Irene Moore Fellowship for Nurse Leaders & Innovators and was inducted as a Fellow in the American Academy of Nursing. Dr. Knisely serves on the Editorial Board for Pain Management Nursing and on the Board of Directors for the American Society for Pain Management Nursing. He is also actively involved in the International Society of Nurses in Genetics, USASP, and IASP.


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