A Final Frontier in Environment-Genome Interactions? Integrated, Multi-Omic Approaches to Predictions of Non-Communicable Disease Risk

Abstract

Epidemiological and associative research from humans and animals identifies correlations between the environment and health impacts. The environment—health inter-relationship is effected through an individual’s underlying genetic variation and mediated by mechanisms that include the changes to gene regulation that are associated with the diversity of phenotypes we exhibit. However, the causal relationships have yet to be established, in part because the associations are reduced to individual interactions and the combinatorial effects are rarely studied. This problem is exacerbated by the fact that our genomes are highly dynamic; they integrate information across multiple levels (from linear sequence, to structural organisation, to temporal variation) each of which is open to and responds to environmental influence. To unravel the complexities of the genomic basis of human disease, and in particular non-communicable diseases that are also influenced by the environment (e.g., obesity, type II diabetes, cancer, multiple sclerosis, some neurodegenerative diseases, inflammatory bowel disease, rheumatoid arthritis) it is imperative that we fully integrate multiple layers of genomic data. Here we review current progress in integrated genomic data analysis, and discuss cases where data integration would lead to significant advances in our ability to predict how the environment may impact on our health. We also outline limitations which should form the basis of future research questions. In so doing, this review will lay the foundations for future research into the impact of the environment on our health.

Nutrition and Health in Human Evolution–Past to Present

“…CNCDs are characterised by the fact that they can be a burden on a person's health for a number of years or decades, or in some cases throughout life. The idea that it is not possible to provide compelling evidence of the transmissibility of a CNCD from one person to another [183] can no longer be supported in view of recent epigenetic insight [184,185]. Epigenetic changes in this context are defined as reactions to external stimuli that lead to pathological dysfunctions and long-term changes in gene expression.…”

“…This has changed and we now have a different understanding of the prevention and treatment of oral diseases [189], due, on the one hand, to new molecular insights into the oral microbiome [190] and a change in how we view the oral biofilm [191] and, on the other, to the fact that confirmed links have been observed between systemic and dental CNCDs [189,192]. These observations have led to various new hypotheses concerning the aetiology and prevention of these diseases, which is why the WHO and the FDI now consider oral health to be a key indicator of overall health [183][184][185][186][187][188][189][190][191][192][193][194][195].…”

Bisphenol-A (BPA) Exposure as a Risk Factor for Non-Communicable Diseases

“…Research on genome regulatory impacts of environmental exposures and their relationship with the risk of NCDs could present some desirable health impacts. Development of polygenic risk scores (PRS) for NCDs, and assigning phenotypic impacts to BPA can help predict an individual's genetic propensity with the BPA exposure risks associated with NCDs traits [81]. Hüls et al [82] demonstrated associations between high PRS for obesity and sociodemographic and lifestyle factors in obese children.…”

The interaction between enhancer variants and environmental factors as an overlooked aetiological paradigm in human complex disease

“…Nonetheless, the interactions between the environment and our genetic make‐up and how these interactions might ultimately influence disease risk are only starting to be elucidated. [ 34 ]…”