Epigenetics and the International Classification of Functioning, Disability and Health Model: Bridging Nature, Nurture, and Patient-Centered Population Health

Abstract

Epigenetic processes enable environmental inputs such as diet, exercise, and health behaviors to reversibly tag DNA with chemical "marks" that increase or decrease the expression of an individual's genetic template. Over time, epigenetic adaptations enable the effects of healthy or unhealthy stresses to become stably expressed in the tissue of an organism, with important consequences for health and disease. New research indicates that seemingly non-biological factors such as social stress, poverty, and childhood hardship initiate epigenetic adaptations in gene pathways that govern inflammation and immunity, two of the greatest contributors to chronic diseases such as diabetes and obesity. Epigenetic processes therefore provide a biological bridge between the genome-an individual's genetic inheritance-and the Social Determinants of Health-the conditions in which they are born, grow, live, work, and age. This Perspective paper argues that physical therapy clinicians, researchers, and educators can use the theoretical framework provided by the International Classification of Functioning, Disability, and Health (ICF model) to harmonize new discoveries from both public health research and medically focused genomic research. The ICF model likewise captures the essential role played by physical activity and exercise, which initiate powerful and widespread epigenetic adaptations that promote health and functioning. In this proposed framework, epigenetic processes transduce the effects of the social determinants of health and behaviors such as exercise into stable biological adaptations that affect an individual's daily activities and their participation in social roles. By harmonizing "nature" and "nurture," physical therapists can approach patient care with a more integrated perspective, capitalizing on novel discoveries in precision medicine, rehabilitation science, and in population-level research. As the experts in physical activity and exercise, physical therapists are ideally positioned to drive progress in the new era of patient-centered population health care.

Keywords: DNA; Genomics; Precision Medicine; Precision Rehabilitation; RNA; Social Determinants of Health.

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1

The ICF model. New discoveries in biology are helping to explain the ways that individual domains influence each other, culminating in function or disability.

Figure 2

The 3 known epigenetic processes (lower left) modify the output of the genome (the transcriptome) in response to a wide range of inputs from the exposome. This has ramifications for the proteome, metabolome, and so on.

Figure 3

(A) The majority of the genome is untranslated (approximately 28%: promotor and enhancer regions) or encodes non-coding RNA (approximately 70%). Only approximately 2% encodes information for producing proteins. (B) A few of the newly discovered functions of non-coding RNA are “SCAFFOLD”: long non-coding RNA (lncRNA) serves as a scaffold on which 2 or more factors connect and carry out a shared function, such as epigenetic modification; “GUIDE”: lncRNA guides other elements to DNA to carry out a function such as gene transcription; and “DECOY”: lncRNA acts as a decoy to block molecular interactions, such as between transcription factors (TF) and their target genes. (C) Micro-RNAs (miRNA) and lncRNA are packaged into extracellular vesicles (exosomes) and released into the circulation where they travel to target cells in distant tissues. There, they exert regulatory effects on the genome and epigenome.

Figure 4

Centers for Disease Control categories and descriptors of the social determinants of health. Adapted from https://www.cdc.gov/socialdeterminants/index.htm.

Figure 5

Epigenetic processes (EP) may biologically mediate the interrelationships among several International Classification of Functioning, Disability, and Health (ICF) domains. Activities (eg, exercise), environmental factors (eg, social determinants of health) and personal factors (eg, smoking, alcohol abuse) may yield epigenetic adaptations of tissues that culminate in positive or negative outcomes in body functions or structures.

Figure 6

Example of International Classification of Functioning, Disability, and Health (ICF) qualifiers that can be used to characterize disability and functioning for a patient with Type 2 diabetes. Epigenetic processes (EP) likely transduce the effects of environmental, personal, and behavioral (activity) factors into tissue-level adaptations that culminate in changes in body structures and function. These changes may, in turn, exacerbate the underlying health condition and trigger further limitations in activities and participation.