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Open research questions in Epigenetics and DNA Methylation

237 unresolved questions extracted from the limitations and future-work sections of 676 Epigenetics and DNA Methylation papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Replication and mechanistic follow-up in larger, state-diverse cohorts is warranted, - Further analysis of the genes associated with DMPs is needed, - Investigation of the mechanisms underlying the associations between epigenetic loci and brain structural changes is necessary

    Novel epigenetic loci identified from an epigenome-wide association study underlying brain structural changes in bipolar disorder · 2026 · DOI

  • The study highlights the gap in understanding the pathophysiology of BD, particularly the role of epigenetic factors. Prior work has focused on genetic variations, but the study aims to investigate epigenetic variations. The study identifies the need for a comprehensive analysis of epigenetic variations in BD.

    Novel epigenetic loci identified from an epigenome-wide association study underlying brain structural changes in bipolar disorder · 2026 · DOI

  • The association between ACEs and biological aging in adolescence remains incompletely understood. Prior studies have relied on cumulative ACE scores, which has limitations. The study aims to address the gap in understanding the association between ACEs and biological aging in adolescence, particularly across intersecting social positions.

    Prospective associations between adverse childhood experiences (ACEs) and biological aging in adolescence · 2026 · DOI

  • The gap is the understanding of how the H3 K36M oncogene affects tumor immune surveillance. The paper identifies a lack of understanding of the role of NSD2 in lung tumor immunity. The study reveals a need to understand the mechanisms by which the H3 K36M oncogene suppresses tumor growth.

    Antagonistic roles of histone H3 lysine methyltransferases dictate tumor immune surveillance · 2026 · DOI

  • intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome, - further examination of the relationship between PTSD and epigenetic aging

    PTSD and epigenetic aging: a longitudinal meta-analysis · 2025 · DOI

  • The association between PTSD and epigenetic aging over time is unclear. There is a need to investigate the relationship between PTSD and epigenetic aging using longitudinal data.

    PTSD and epigenetic aging: a longitudinal meta-analysis · 2025 · DOI

  • the association between epigenetic ageing and PLEs was no longer significant after adjusting for smoking - the study used a longitudinal approach but had a limited number of time points - the study controlled for sex, array, and cell type composition scores but not other potential confounders

    The association between epigenetic ageing from childhood to early adulthood and psychotic-like experiences in early adulthood · 2025 · DOI

  • The long-term relationship between epigenetic ageing and psychotic-like experiences remains largely unclear. There is a need to understand the developmental pathways to psychotic-like experiences in order to develop predictive markers of risk. Current research has not fully explored the use of epigenetic clocks in predicting psychotic-like experiences.

    The association between epigenetic ageing from childhood to early adulthood and psychotic-like experiences in early adulthood · 2025 · DOI

  • Investigation of microbiome-host epigenome interactions at high resolution, - Development of biomarker discovery and live biotherapeutic interventions, - Exploration of adaptive clinical trial designs

    The Gut Microbiome and Epigenomic Reprogramming: Mechanisms, Interactions, and Implications for Human Health and Disease · 2025 · DOI

  • The underlying molecular pathways through which gut microbiota regulate host methylation patterns are not fully understood. The impact of host factors such as aging, diet, immune activity, and sociocultural context on microbial composition and function is not well characterized.

    The Gut Microbiome and Epigenomic Reprogramming: Mechanisms, Interactions, and Implications for Human Health and Disease · 2025 · DOI

  • the study only used male C57BL/6 J mice, - the study excluded maternal gestational effects and any confounding influences from females, - the operation of animals was limited during the whole experiment, - the animals suffered less pain according to the pain classification

    Paternally multi-generational high-fat diet causes obesity and metabolic disorder through intergenerational DNA methylation · 2025 · DOI

  • further studies are needed to investigate the underlying mechanisms associated with sustained multigenerational HFD exposure, - the effects of paternal HFD on female offspring should be investigated, - the intergenerational transmission of metabolic disorders should be further studied

    Paternally multi-generational high-fat diet causes obesity and metabolic disorder through intergenerational DNA methylation · 2025 · DOI

  • Yet even as empirical datasets accumulate exponentially, the mechanistic underpinnings of epigenetic changes and their role in connecting environmental variation with the regulation of gene function remain unclear.

    Epigenetic Intelligence: How Organisms Track Their Environment Through Molecular Memory · 2026 · DOI

  • Despite extensive molecular characterization, mechanisms and precise contributions of DNMT-specific methylation in native cellular contexts remain elusive.

    Live-cell DNMT3A “catalysome” mapping using engineered methyl-transfer pathways · 2026 · DOI

  • In particular, studies exploring commonalities and differences across diagnoses are lacking.

    Blood-based DNA methylation profiles in major depressive disorder, bipolar disorder, and schizophrenia spectrum disorders · 2025 · DOI

  • However, the genetic architecture and reliable targets for brain aging remains poorly understood.

    Genetically supported targets and drug repurposing for brain aging: A systematic study in the UK Biobank · 2025 · DOI

  • Whether and how glutaminolysis might enhance lactate production and facilitate DNA repair in cancer cells remains unknown.

    ACAT1‐Mediated ME2 Acetylation Drives Chemoresistance in Ovarian Cancer by Linking Glutaminolysis to Lactate Production · 2025 · DOI

  • Although lactate is shown to influence macrophage functions via histone lactylation, the specific functions of MCTs in macrophages remain incompletely understood.

    MCT1‐mediated Lactate Shuttle to Mitochondria Governs Macrophage Polarization and Modulates Glucose Homeostasis by Affecting β Cells · 2025 · DOI

  • However, the molecular mechanisms underlying the cardioprotective effects of exercise are still not fully understood.

    Role of physical activity in cardiovascular disease prevention: impact of epigenetic modifications · 2025 · DOI

  • BPA is a globally ubiquitous industrial compound that harms male reproductive health by causing abnormal sperm development and subsequent spermatogonia loss, yet the underlying mechanisms of BPA-induced spermatogenesis disorder remain unclear.

    Bisphenol A Disrupts Spermatogenesis via Excessive Mitophagy-Driven Ferroptosis · 2025 · DOI

  • Despite its significant clinical impact, the biological mechanisms underlying cognitive impairment in BD remain poorly understood, complicating treatment efforts.

    Association between GRIN2B DNA methylation and cognitive impairment: a cross-sectional study of patients with bipolar depression · 2025 · DOI

  • This gap is even more pronounced in mitochondrial epigenetics, despite mitochondria’s critical role in energy production and growth regulation, making it an important but underexplored area in aquaculture breeding strategies.

    Mitochondrial methylation is linked to sexually dimorphic growth in Nile tilapia (Oreochromis niloticus) · 2025 · DOI

  • While de novo DNA methylation is known to enforce T cell exhaustion, the role of histone modifications in shaping these methylation patterns remains unclear.

    Histone demethylases KDM5A/B regulate epigenetic programming of exhausted T cells and restrain immunotherapy responses 4207 · 2025 · DOI

  • Epigenetic factors, including histone modifications, are increasingly recognized as key determinants of immune responses; however, the immunomodulatory function of EZH2 in BAEC remains unknown.

    EZH2 is a molecular determinant of epithelial cell hyperresponsiveness and severe airway disease 4524 · 2025 · DOI

  • Despite its significant global burden, the underlying mechanisms of immune dysfunction in sepsis remain incompletely understood.

    Epigenome-wide DNA methylation profiling in septic and non-septic patients with similar infections: potential use as sepsis biomarkers · 2025 · DOI

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237 open questions have been extracted from the limitations and future-work passages of 676 Epigenetics and DNA Methylation papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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