Epigenetics and the exposome: DNA methylation as a proxy for health impacts of prenatal environmental exposures

Colwell, Mathia; Townsel, Courtney; Petroff, Rebekah; Goodrich, Jaclyn M.; Dolinoy, Dana C.

doi:10.1093/exposome/osad001

Cited by 16 publications

(10 citation statements)

References 110 publications

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“…Considerations of reproductive, pregnancy, and placental exposomes influence evaluations of MPF triads, neonates, children, and adults. Diseases and adversities throughout the lifetime are represented by a dynamic neural exposome ( 4 ) ( Figure 1 ). This life-course perspective will require novel multimodal biomarkers to select more effective preventive, rescue, and reparative neuroprotective interventions with advancing ages.…”

Section: Introduction: the Neural Exposome Concept Applied To Fetal N...mentioning

confidence: 99%

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Interdisciplinary fetal-neonatal neurology training applies neural exposome perspectives to neurology principles and practice

Scher

2024

Front. Neurol.

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An interdisciplinary fetal-neonatal neurology (FNN) program over the first 1,000 days teaches perspectives of the neural exposome that are applicable across the life span. This curriculum strengthens neonatal neurocritical care, pediatric, and adult neurology training objectives. Teaching at maternal-pediatric hospital centers optimally merges reproductive, pregnancy, and pediatric approaches to healthcare. Phenotype–genotype expressions of health or disease pathways represent a dynamic neural exposome over developmental time. The science of uncertainty applied to FNN training re-enforces the importance of shared clinical decisions that minimize bias and reduce cognitive errors. Trainees select mentoring committee participants that will maximize their learning experiences. Standardized questions and oral presentations monitor educational progress. Master or doctoral defense preparation and competitive research funding can be goals for specific individuals. FNN principles applied to practice offer an understanding of gene–environment interactions that recognizes the effects of reproductive health on the maternal-placental-fetal triad, neonate, child, and adult. Pre-conception and prenatal adversities potentially diminish life-course brain health. Endogenous and exogenous toxic stressor interplay (TSI) alters the neural exposome through maladaptive developmental neuroplasticity. Developmental disorders and epilepsy are primarily expressed during the first 1,000 days. Communicable and noncommunicable illnesses continue to interact with the neural exposome to express diverse neurologic disorders across the lifespan, particularly during the critical/sensitive time periods of adolescence and reproductive senescence. Anomalous or destructive fetal neuropathologic lesions change clinical expressions across this developmental-aging continuum. An integrated understanding of reproductive, pregnancy, placental, neonatal, childhood, and adult exposome effects offers a life-course perspective of the neural exposome. Exosome research promises improved disease monitoring and drug delivery starting during pregnancy. Developmental origins of health and disease principles applied to FNN practice anticipate neurologic diagnoses with interventions that can benefit successive generations. Addressing health care disparities in the Global South and high-income country medical deserts require constructive dialogue among stakeholders to achieve medical equity. Population health policies require a brain capital strategy that reduces the global burden of neurologic diseases by applying FNN principles and practice. This integrative neurologic care approach will prolong survival with an improved quality of life for persons across the lifespan confronted with neurological disorders.

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Section: Introduction: the Neural Exposome Concept Applied To Fetal N...mentioning

confidence: 99%

“…Exposures during childhood, adolescence, and adulthood may impart additional epigenetic alterations. Reprinted with permission Colwell et al ( 4 ) licensed under CC by 4.0.…”

Section: Introduction: the Neural Exposome Concept Applied To Fetal N...mentioning

confidence: 99%

Interdisciplinary fetal-neonatal neurology training applies neural exposome perspectives to neurology principles and practice

Scher

2024

Front. Neurol.

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“…For example, dairy consumption and plasma urate levels have been associated with PD risk, but no epigenetic studies have been conducted in humans yet 87 , 127 . Future work will also benefit from more comprehensively exploring the exposome 128 and epigenetic signatures associated with it, providing insights into the cumulative effects of multiple exposures and their collective contribution to disease development and progression.…”

Section: Discussionmentioning

confidence: 99%

Linking environmental risk factors with epigenetic mechanisms in Parkinson’s disease

Tsalenchuk,

Gentleman,

Marzi

2023

npj Parkinsons Dis.

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Sporadic Parkinson’s disease (PD) is a progressive neurodegenerative disease, with a complex risk structure thought to be influenced by interactions between genetic variants and environmental exposures, although the full aetiology is unknown. Environmental factors, including pesticides, have been reported to increase the risk of developing the disease. Growing evidence suggests epigenetic changes are key mechanisms by which these environmental factors act upon gene regulation, in disease-relevant cell types. We present a systematic review critically appraising and summarising the current body of evidence of the relationship between epigenetic mechanisms and environmental risk factors in PD to inform future research in this area. Epigenetic studies of relevant environmental risk factors in animal and cell models have yielded promising results, however, research in humans is just emerging. While published studies in humans are currently relatively limited, the importance of the field for the elucidation of molecular mechanisms of pathogenesis opens clear and promising avenues for the future of PD research. Carefully designed epidemiological studies carried out in PD patients hold great potential to uncover disease-relevant gene regulatory mechanisms. Therefore, to advance this burgeoning field, we recommend broadening the scope of investigations to include more environmental exposures, increasing sample sizes, focusing on disease-relevant cell types, and recruiting more diverse cohorts.

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“…The epigenome, which describes modifications (e.g. CpG methylation, histone acetylation) to cellular DNA that do not include changes to its nucleotide sequence [ 136 ], is often considered a biological proxy of the exposome [ 137 ].…”

Section: The Organization Of Mental Health Researchmentioning

confidence: 99%

Whole Person Modeling: a transdisciplinary approach to mental health research

Felsky,

Cannitelli,

Pipitone

2023

Discov Ment Health

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The growing global burden of mental illness has prompted calls for innovative research strategies. Theoretical models of mental health include complex contributions of biological, psychosocial, experiential, and other environmental influences. Accordingly, neuropsychiatric research has self-organized into largely isolated disciplines working to decode each individual contribution. However, research directly modeling objective biological measurements in combination with cognitive, psychological, demographic, or other environmental measurements is only now beginning to proliferate. This review aims to (1) to describe the landscape of modern mental health research and current movement towards integrative study, (2) to provide a concrete framework for quantitative integrative research, which we call Whole Person Modeling, (3) to explore existing and emerging techniques and methods used in Whole Person Modeling, and (4) to discuss our observations about the scarcity, potential value, and untested aspects of highly transdisciplinary research in general. Whole Person Modeling studies have the potential to provide a better understanding of multilevel phenomena, deliver more accurate diagnostic and prognostic tests to aid in clinical decision making, and test long standing theoretical models of mental illness. Some current barriers to progress include challenges with interdisciplinary communication and collaboration, systemic cultural barriers to transdisciplinary career paths, technical challenges in model specification, bias, and data harmonization, and gaps in transdisciplinary educational programs. We hope to ease anxiety in the field surrounding the often mysterious and intimidating world of transdisciplinary, data-driven mental health research and provide a useful orientation for students or highly specialized researchers who are new to this area.

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Epigenetics and the exposome: DNA methylation as a proxy for health impacts of prenatal environmental exposures

Cited by 16 publications

References 110 publications

Interdisciplinary fetal-neonatal neurology training applies neural exposome perspectives to neurology principles and practice

Interdisciplinary fetal-neonatal neurology training applies neural exposome perspectives to neurology principles and practice

Linking environmental risk factors with epigenetic mechanisms in Parkinson’s disease

Whole Person Modeling: a transdisciplinary approach to mental health research

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