Characterizing epigenetic aging in an adult sickle cell disease cohort.
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2024-01
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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.Type
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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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Qing Yang
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.
Nirmish Ramesh Shah
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