Clinical Epigenetics最新文献

{"title":"First evidence of epigenetic modulation of human gene methylation by microalga Aphanizomenon flos-aquae (AFA) in inflammation-related pathways in intestinal cells.","authors":"Flores Naselli, Sara Volpes, Paola Sofia Cardinale, Sabrina Micheli, Adele Cicio, Gabriel Dylan Scoglio, Roberto Chiarelli, Maria Grazia Zizzo, Pasquale Picone, Fabio Caradonna, Domenico Nuzzo","doi":"10.1186/s13148-025-01849-5","DOIUrl":"10.1186/s13148-025-01849-5","url":null,"abstract":"<p><p>The microalga Aphanizomenon flos-aquae (AFA) has garnered attention for its potential therapeutic benefits in various health conditions, primarily through its use in nutraceutical formulations. While biological effects of AFA have been extensively studied in preclinical models, including murine systems, its nutrigenomic and epigenetic impacts remain underexplored. This study investigates the potential epigenetic mechanisms of AFA, focusing on its ability to modulate DNA methylation, a key regulatory process in gene expression. Specifically, we examined the influence of AFA on the methylation status of genes encoding pro-inflammatory interleukins, as these cytokines play a crucial role in immune response modulation and inflammation. Given the known impact of AFA on inflammatory markers, we aimed to determine whether the effects of AFA involve direct or indirect modulation of DNA methylation patterns in genes associated with inflammation. Our findings, presented here for the first time, reveal the capacity of AFA to influence DNA methylation, with implications for its role in cellular regulatory processes. These results warrant further investigation into precise mechanisms of action of AFA and its potential in clinical applications targeting inflammation-related pathways.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"44"},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein epigenetic scores and overall mortality in the longitudinal Swedish Adoption/Twin Study of Aging (SATSA).","authors":"Thaís Lopes De Oliveira, Arianna March, Jonathan K L Mak, Nancy L Pedersen, Sara Hägg","doi":"10.1186/s13148-025-01843-x","DOIUrl":"10.1186/s13148-025-01843-x","url":null,"abstract":"<p><strong>Introduction: </strong>DNA methylation (DNAm) has a functional role in gene regulation, and it has been used to estimate various human characteristics. Variation in DNAm is associated with aging and variability of the proteome. Therefore, understanding the relationship between blood circulating proteins, aging, and mortality is critical to identify disease-causing pathways. We aimed to estimate the association between protein epigenetic scores (EpiScores) and overall mortality in the Swedish Adoption/Twin Study of Aging (SATSA).</p><p><strong>Methods: </strong>We included information from 374 individuals collected between 1992 and 2014. Our exposures were 109 protein EpiScores generated using DNAm data and prediction models by the MethylDetectR shiny app. All-cause mortality was the outcome of interest. To estimate the protein EpiScores associations with all-cause mortality, we fitted Cox proportional hazard models adjusted for age, sex, education, smoking status, body mass index, and occupation. We also conducted co-twin control analyses to control for shared familial factors.</p><p><strong>Results: </strong>The mean age of participants at the first assessment was 68.6 years. In total, nine protein EpiScores (e.g., Stanniocalcin 1) were associated with a higher risk for all-cause mortality. In contrast, five protein EpiScores (e.g., Prolyl endopeptidase) were associated with a lower risk for all-cause mortality.</p><p><strong>Conclusion: </strong>The protein EpiScores associated with an increased mortality risk represent proteins involved in metabolic functions, immune response, and inflammation. Conversely, those associated with a lower risk represent proteins involved in neurogenesis and cellular functions. Overall, it is possible to predict protein levels from DNAm data that could have clinical relevance.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"41"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mendelian randomization provides a multi-omics perspective on the regulation of genes involved in ribosome biogenesis in relation to cardiac structure and function.","authors":"Shuxu Wei, Ronghuai Shen, Xiaojia Lu, Xinyi Li, Lingbin He, Youti Zhang, Jiahang Yang, Zhouwu Shu, Xianxi Huang","doi":"10.1186/s13148-025-01850-y","DOIUrl":"10.1186/s13148-025-01850-y","url":null,"abstract":"<p><strong>Background: </strong>Ribosome biogenesis (RiboSis) is a complex process for generating ribosomes, the cellular machinery responsible for protein synthesis. Dysfunctional RiboSis can disrupt cardiac structure and function, contributing to cardiovascular diseases. This study employed a Mendelian randomization (MR) approach, integrating multi-omics data, to investigate the relationship between RiboSis-related genes and standard cardiac structure and function.</p><p><strong>Methods: </strong>We utilized summary stats for methylation, RNA splicing, and gene expression, and UK Biobank cardiopulm MRI genetic associations (N = 41,135). MR evaluated RiboSis gene features against traits, complemented by hypothesis prioritization for multi-trait colocalization (HyPrColoc) and colocalization. Composite scores ranked RiboSis genes, and phenome-wide association study (PheWAS) with scQTLbase instrumental variables (IVs) confirmed results.</p><p><strong>Results: </strong>We identified 15 RiboSis-related genes: HEATR1, SENP3, ERI1, ERCC2, TSR1, UTP11, DDX17, SMARCB1, NIP7, ERAL1, NOP56, RPL10A, EIF6, EXOSC9, and NOP58. Notably, HEATR1 and SENP3 were ranked in the top quartile (Q1), scoring 25. In validation cohort, 12 genes associated with cardiac structures, functions, diseases. Only ERAL1, TSR1, and NIP7 lacked significant associations with cardiac traits.</p><p><strong>Conclusion: </strong>Our multi-omics MR analysis identified 15 RiboSis-related genes associated with cardiac risk, with 12 further validated through gene set enrichment analysis. These findings suggest a link between RiboSis and cardiac health, enhancing understanding of cardiac disease mechanisms.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"42"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting the causal effects of smoking, alcohol consumption, and related DNA methylation markers on electrocardiographic indices.","authors":"Zequn Zheng, Yongfei Song, Xinhan Li, Tao Luo, Xuerui Tan","doi":"10.1186/s13148-025-01851-x","DOIUrl":"10.1186/s13148-025-01851-x","url":null,"abstract":"<p><strong>Background: </strong>Tobacco and alcohol are recognized risk factors for heart disease, yet their causal effects on electrocardiogram (ECG) signaling and mechanisms remain unclear. Previous studies may be susceptible to confounding or bias, and this study dissected the genetic architecture linking tobacco and alcohol consumption with P-wave duration, PR interval, and QT interval.</p><p><strong>Methods: </strong>Utilizing genetic instruments for tobacco and alcohol consumption, associated methylation quantitative trait locus (mQTL), and summary-level GWAS data for ECG indices, we assessed heritability and genetic causal associations using linkage disequilibrium score regression and Mendelian randomization (MR) analysis. Fine mapping was performed via colocalization analysis and summary-data-based MR (SMR) to identify potential shared genetic variants.</p><p><strong>Results: </strong>A positive causal relationship was found between drinks per week (DrnkWk) and QT interval [β (95%CI): 1.06 (0.91, 5.05), P = 0.005], with causality substantiated through multiple robust MR models. Multivariable MR confirmed independence from smoking phenotypes. In epigenetic MR analyses, two alcohol-related CpG loci (cg03345232 and cg04605617) were causally associated with QT interval changes, with cg04605617 mapping to PLA2G2C gene significantly prolonging QT. The mQTL rs10916683 at cg04605617 is a strong eQTL for PLA2G2C. Additionally, cg03345232 shared a causal variant (rs12881206) with QT interval predisposition through colocalization analysis. SMR analysis did not identify shared putative functional genes passing the HEIDI test between DrnkWk and the QT interval.</p><p><strong>Conclusions: </strong>There is a causal relationship between DrnkWk and QT interval prolongation, and targeting specific DNA methylation sites like cg04605617 mapped to PLA2G2C may provide novel targets for preventing QT interval prolongation.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"40"},"PeriodicalIF":4.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in epigenetic treatment of adult T-cell leukemia/lymphoma: a comprehensive review.","authors":"Arash Letafati, Rabeeh Mehdigholian Chaijani, Fahime Edalat, Nazila Eslami, Hanieh Askari, Farideh Askari, Sara Shirvani, Hamed Talebzadeh, Mahdiyeh Tarahomi, Nila MirKhani, Faeze Karimi, Mehdi Norouzi, Sayed-Hamidreza Mozhgani","doi":"10.1186/s13148-025-01841-z","DOIUrl":"10.1186/s13148-025-01841-z","url":null,"abstract":"<p><p>Human T-cell lymphotropic virus type 1 (HTLV-1) infection causes the uncommon and deadly cancer known as adult T-cell leukemia/lymphoma (ATLL), which affects mature T cells. Its clinical appearance is varied, and its prognosis is often miserable. Drug resistance to conventional therapies confers significant therapeutic challenges in the management of ATLL. This review discusses the emerging role of epigenetic medical advances in the treatment of ATLL, focusing on DNA methyltransferase inhibitors, histone deacetylase inhibitors, histone methyltransferase inhibitors, and BET inhibitors. Indeed, several classes of epigenetic therapies currently exhibit trailed efficacy in preclinical and clinical studies: DNA methyltransferase inhibitors like azacitidine and decitabine reexpression of silenced tumor suppressors; histone deacetylase inhibitors like vorinostat and romidepsin induce cell cycle arrest and apoptosis; bromodomain and extra-terminal inhibitors like JQ1 disrupt oncogenic signaling pathways. Whereas preclinical and early clinical data indicate modest to good efficacy for such treatments, significant challenges remain. Here, we discuss the current state of understanding of epigenetic dysregulation in ATLL and appraise the evidence supporting the use of these epi-drugs. However, despite the opened doors of epigenetic treatment, much more research is required with regard to showing the best combinations of drugs and their resistance mechanisms, the minimization of adverse effects, and how this hope will eventually be translated into benefit for the patient with ATLL.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"39"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma cfDNA VILL gene methylation as a diagnostic marker for nasopharyngeal carcinoma.","authors":"Xiao-Yan Fu, Zi-Ying Zhou, Teng-Yue Yang, Ying-Juan Wen, Da-Bo Liu, Yi-Bo Zhou, Yuan Yue, Fei Ye, Zhong-Xi Huang","doi":"10.1186/s13148-025-01847-7","DOIUrl":"10.1186/s13148-025-01847-7","url":null,"abstract":"<p><p>Currently, the non-invasive diagnostic methods for nasopharyngeal carcinoma (NPC) continue to grapple with the challenge of low sensitivity. The hypermethylation of tumor suppressor genes is an established early event in NPC pathogenesis. Consequently, we conducted whole-genome methylation sequencing on plasma cell-free DNA (cfDNA) from six NPC cases and four healthy controls, integrating Illumina Human Methylation 450 K microarray data from the GEO database comprising six NPC cases and six samples of non-cancerous nasopharyngeal tissue (NP). As result, we screened only one CpG island associated with cell type-specific regulation within the candidate tumor suppressor gene VILL (Vilin Like), which exhibits specific methylation patterns in NPC. We validated our findings using 25 pairs of NPC and NP samples from GEO, alongside 9,736 pan-cancer tissues from TCGA and 656 healthy human leukocyte samples sourced from GEO through methylation microarray analysis. Based on this, we designed a methylation-specific qPCR (qMSP) system for the VILL gene, and then tested it on 192 primary NPC and 154 NC plasma samples. The new qMSP system when compared with EBV DNA qPCR revealed a sensitivity for primary NPC of 80.2% vs.81.3% (78.8% vs.54.5% for early-stage NPC), and a specificity of 100% vs. 93.5%. Notably, employing a combined methodology further enhanced sensitivity to 94.8%, including a sensitivity rate of 90.9% for early-stage NPC diagnosis. Therefore, VILL methylation assessment combined with EBV DNA detection presents a promising avenue for non-invasive diagnosis of NPC, particularly beneficial for early detection.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"38"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HDAC inhibitors modulate Hippo pathway signaling in hormone positive breast cancer.","authors":"Ting-I Lin, Yi-Ru Tseng, Min-Jyun Dong, Chih-Yi Lin, Wei-Ting Chung, Chun-Yu Liu, Yi-Fang Tsai, Chi-Cheng Huang, Ling-Ming Tseng, Ta-Chung Chao, Jiun-I Lai","doi":"10.1186/s13148-025-01834-y","DOIUrl":"10.1186/s13148-025-01834-y","url":null,"abstract":"<p><p>Breast cancer has constantly been the leading causes of death in women, and hormone receptor (HR) positive, HER2 negative is the majority subtype. Histone deacetylase (HDAC) inhibitors (HDACi) have shown clinical benefit in HR ( +) breast cancer patients. The Hippo pathway is an important cellular pathway involving proliferation, cell contact, and cancer. Hippo pathway proteins YAP/TAZ are often viewed as pro-tumorigenic; however, recent studies support a role of YAP as a tumor suppressor in HR ( +) breast cancer. Few studies have investigated the link between HDACi and the Hippo pathway. In our study, we demonstrate that HDACi induces transcriptional downregulation of YAP expression, while conversely activating a TEAD-mediated transcriptional program with upregulation of canonical Hippo pathway genes. We subsequently identified four Hippo canonical genes (CCDC80, GADD45A, F3, and TGFB2) that were upregulated by HDACi and associated with significantly improved survival in a HR ( +) breast cancer cohort. We further validated experimentally that HR ( +) breast cancer cells treated with HDACi resulted in upregulation of CCDC80 and GADD45A. A pan-cancer analysis of TCGA database demonstrated lower CCDC80 and GADD45A expression in tumor tissue compared to non-tumor samples in BRCA (breast cancer), LAML (acute myeloid leukemia), and UCS (uterine carcinosarcoma). Further analysis of HR ( +) breast cancer patients in the METABRIC dataset revealed high CCDC80 and/or GADD45A expression associated with significantly better survival outcomes compared to patients with low expression. Our study provides evidence for a novel mechanism of HDACi clinical activity, as well as a potential role for CCDC80 and GADD45A in HR ( +) breast cancer.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"37"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging and outcome correlates of ctDNA methylation markers in prostate cancer: a comparative, cross-sectional [⁶⁸Ga]Ga-PSMA-11 PET/CT study.","authors":"Kilian Kluge, Vincent Lotz, Holger Einspieler, David Haberl, Clemens Spielvogel, Dominik Amereller, Gero Kramer, Bernhard Grubmüller, Shahrokh Shariat, Alexander Haug, Marcus Hacker, Lukas Kenner, Gerda Egger","doi":"10.1186/s13148-025-01811-5","DOIUrl":"10.1186/s13148-025-01811-5","url":null,"abstract":"<p><strong>Background: </strong>To validate the clinical utility of a previously identified circulating tumor DNA methylation marker (meth-ctDNA) panel for disease detection and survival outcomes, meth-ctDNA markers were compared to PSA levels and PSMA PET/CT findings in men with different stages of prostate cancer (PCa).</p><p><strong>Methods: </strong>122 PCa patients who underwent [⁶⁸Ga]Ga-PSMA-11 PET/CT and plasma sampling (03/2019-08/2021) were analyzed. cfDNA was extracted, and a panel of 8 individual meth-ctDNA markers was queried. PET scans were qualitatively and quantitatively assessed. PSA and meth-ctDNA markers were compared to PET findings, and their relative prognostic value was evaluated.</p><p><strong>Results: </strong>PSA discriminated best between negative and tumor-indicative PET scans in all (AUC 0.77) and hormone-sensitive (hsPC) patients (0.737). In castration-resistant PCa (CRPC), the meth-ctDNA marker KLF8 performed best (AUC 0.824). CHST11 differentiated best between non- and metastatic scans (AUC 0.705) overall, KLF8 best in hsPC and CRPC (AUC 0.662, 0.85). Several meth-ctDNA markers correlated low to moderate with the tumor volume in all (5/8) and CRPC patients (6/8), while PSA levels correlated moderately to strongly with the tumor volume in all groups (all p < 0.001). CRPC overall survival was independently associated with LDAH and PSA (p = 0.0168, p < 0.001).</p><p><strong>Conclusion: </strong>The studied meth-ctDNA markers are promising for the minimally-invasive detection and prognostication of CRPC but do not allow for clinical characterization of hsPC. Prospective studies are warranted for their use in therapy response and outcome prediction in CRPC and potential incremental value for PCa monitoring in PSA-low settings.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"36"},"PeriodicalIF":4.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles and mechanisms of histone methylation in vascular aging and related diseases.","authors":"Yufei Ji, Zhenzhen Chen, Jun Cai","doi":"10.1186/s13148-025-01842-y","DOIUrl":"10.1186/s13148-025-01842-y","url":null,"abstract":"<p><p>The global aging trend has posed significant challenges, rendering healthcare for older adults a crucial focus in medical research. Among the numerous health concerns related to aging, vascular aging and dysfunction are important risk factors and underlying causes of age-related diseases. Histone methylation and demethylation, which are involved in gene expression and cellular senescence, are closely associated with the occurrence and development of vascular aging. Consequently, this review aimed to identify the role of histone methylation in the pathogenesis of vascular aging and its potential for treating age-related vascular diseases and provided new insights into therapeutic strategies targeting the vascular system.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"35"},"PeriodicalIF":4.8,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Black community member perceptions and ethics recommendations on epigenomic research.","authors":"Courtney Berrios, Tammy Basey, Andrea Bradley-Ewing, Stacey Daniels-Young, Daysha Lewis, Keith Feldman, Mary E Moffatt, Tomi Pastinen, Elin Grundberg","doi":"10.1186/s13148-025-01840-0","DOIUrl":"10.1186/s13148-025-01840-0","url":null,"abstract":"<p><strong>Background: </strong>Social epigenomics research investigates links between social experiences and epigenetic modifications, which may ultimately impact health. Such research holds promise for precision medicine and addressing health disparities based on social conditions, but also brings unique ethical challenges. The linking of social experiences to biological changes risks pathologizing experiences, potentially leading individuals and communities to be seen as 'damaged.' This stigmatization or stereotyping based on experiences also risks placing disproportionate personal responsibility for health. These risks are likely to be amplified in historically marginalized communities already facing discrimination. It is therefore essential to engage members of historically marginalized communities to explore attitudes about social epigenomics research. This study focuses on the Black and African American (B/AA) population in the USA, studying perceptions of social epigenomic research participants, research decliners, and broadly representative community members to identify perceived benefits and risks of social epigenomic research as well as strategies to maximize benefits and lower risks for both participants and communities.</p><p><strong>Results: </strong>Both research participants and community members perceived potential benefit of social epigenomic research for the B/AA population. While most research participants did not perceive research related risks, community members identified risks both specific to social epigenomic research and more generalized to medical research. Several of the risks identified, and a belief that the likelihood of harms was greater than the likelihood of benefits, were based on past research injustices to B/AA research participants and mistrust in the medical and research enterprise. However, community members provided concrete strategies for maximizing the chance of benefits and lowering risk of harms including acknowledging and addressing biases and past injustices, ensuring transparency and understanding, positive framing of research, thorough research and dissemination, and engaging with communities before, throughout, and beyond the research process.</p><p><strong>Conclusions: </strong>While B/AA community members identified risk of both individual and community harm from social epigenomic research, they also perceived potential health benefits for the B/AA community. Through concerted efforts to apply community recommendations to lower risks and enhance benefits, researchers can conduct ethical and valid epigenomic research that aims to address health disparities with historically marginalized communities.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"33"},"PeriodicalIF":4.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}