Epigenetics : Possible Cause of Intergenerational Trauma

Introduction

For years, scientists have been trying to explain variance and inheritance through genetics with laws like Mendelian genetics laws or Law of Independent Assortment but the conundrum is that two identical twins with the exact genetic material can also look different even in traits that have a significant genetic component. For example, one twin might get a heart disease at 55 while the other twin runs marathons in perfect health. Scientists have been connecting these differences with the difference in their environments or more known as the concept of ‘nature vs nurture’. The deeper related answer can be found within a concept called ’epigenetics’.

Main Context 

What is Epigenetics?

Epigenetics is the study of how DNA interacts with smaller molecules found within cells which could change gene expression that cannot be explained by changes in DNA sequence. These smaller molecules refer to epigenetic molecular factors or epigenetic marks. The set of all of the epigenetic marks that are attached to the genome of a given cell is called ‘epigenome’. Epigenetics tells us that changes in gene expression do not always involve DNA mutations or DNA sequence manipulation especially when our genome is actually very chemically stable.

Environmentally-induced epigenetic changes are part of the reason why genetically identical twins can grow up to have very different lives. As twins get older, their epigenomes diverge affecting the way they age and their susceptibility to disease. 

The term epigenetics was coined by Conrad Waddington in the 1940s. Waddington integrated the new knowledge about genes and genetics to embryology. The study of embryological growth and differentiation was commonly known as Epigenesis, a concept that was around since Aristotelian times. The integration of the concepts of Epigenesis and Genetics gave origin to the term Epigenetics. Waddington’s goal with epigenetics was to provide insight into gene-environment interactions that influence development and embryology.

Types of Epigenetic Marks

1. DNA methylation

DNA methylation was identified as the first epigenetic molecular factor in the 1970s and related most to X chromosome inactivation. Proteins are attracted to methylated parts of DNA and promote or inhibit the recruitment of transcription machinery.

2. Histone modifications

Histone modification was identified in the mid 1990s and largely contributed to the appreciation of chromatin structure in the regulation of the genome. It can happen through various processes like acetylation and methylation which either promotes or inhibits transcription.

Why does epigenetics matter?

Even social experiences can cause epigenetic changes. In one famous experiment, when mother rats were not attentive enough to their pups, genes in the pups that help them to manage stress underwent epigenetic changes like DNA methylation and the genes were turned off. The change in gene expression might not stop with that generation because some of those epigenetic traits survive and pass on to the next generation. The ability of the environment to affect not only the individual exposed but also in subsequent descendants for multiple generations is termed ‘transgenerational inheritance’.This means our mother or our father’s experiences as a child or choices as adults could actually shape our own epigenome.

A Case Study of Epigenetics

A case study shows that maternal trauma influences infant and adult health outcomes and may impact future generations through epigenetic modifications such as DNA methylation (DNAm). Using epigenome-wide association study (EWAS), this study assessed the DNAm signatures of war-related violence by comparing germline, prenatal, and direct exposures to violence across three generations of Syrian refugees. They compared families in which a pregnant grandmother versus a pregnant mother was exposed to violence and included a control group with no exposure to war. They identified differentially methylated regions and most of them showed the same directionality in DNAm change across germline, prenatal, and direct exposures, suggesting a common epigenetic response to violence. This was the first report of an intergenerational epigenetic signature of violence, which has important implications for understanding the inheritance of trauma.

Myth of Transgenerational Inheritance in Humans

In principle, epigenetic inheritance and germline reprogramming are two sides of the same coin because somatic cells are separated from germ cells and thus no mechanisms were thought to exist for germ cells to be modified by the environment. Germline reprogramming is the essential, large-scale erasure and reset of epigenetic marks (DNA methylation and histone modifications) in germ cells (sperm and eggs) and early embryos so that the embryo properly reflects the genetic blueprint characteristic of each species. This means that only if germline reprogramming fails, epigenetic marks can be retained, and could be transmitted from one generation to the next.

Although the mammalian epigenome is wiped clean of most DNAm marks during gametogenesis and embryogenesis to allow epigenetic reprogramming, there is intriguing support from animal models for environmentally-induced epigenetic marks that resist epigenetic reprogramming and are intergenerationally and transgenerationally inherited with phenotypic effects. Transgenerational epigenetic inheritance is well-documented in yeast, plants, fish, Caenorhabditis elegans and Drosophila. There are fewer examples of epigenetic inheritance in animal models, but a recent study reported DNAm inheritance in mice up to four generations. In contrast, only a single study in humans has reported associations of trauma exposure in grandmothers with DNAm changes in grandchildren.

Challenges and LImitations of this Study

The study of epigenetic inheritance in humans is complicated because of the difficulty of conducting multigenerational, experimentation studies as well as the importance of cultural and environmental factors. Overall, the changes in DNAm in humans following fertilization which are important in early development are complex and intricately timed.

Conclusion

It is an exciting time to be studying the possibility of epigenetic inheritance as epigenetics could explain how conditions like cancer, heart disease, mental illness and addiction are inherited throughout generations. It could also explain the dramatic and rapid increase in nearly all disease frequencies over the past several decades that can not be explained through genetics alone. Once we understand how our epigenome influences us, we might be able to influence it too. Especially with the new genome editing techniques available that make it much easier by identifying which epigenetic changes matter for health and disease.

References 

Mulligan, C.J., Quinn, E.B., Hamadmad, D., Dutton, C.L., Nevell, L., Binder, A.M., Panter-Brick, C. and Dajani, R. (2025). Epigenetic signatures of intergenerational exposure to violence in three generations of Syrian refugees. Scientific Reports, [online] 15(1). doi:https://doi.org/10.1038/s41598-025-89818-z.

Skinner, M.K., Manikkam, M. and Guerrero-Bosagna, C. (2010). Epigenetic transgenerational actions of environmental factors in disease etiology. Trends in Endocrinology & Metabolism, 21(4), pp.214–222. doi:https://doi.org/10.1016/j.tem.2009.12.007.

TED-Ed (2016). What is epigenetics? - Carlos Guerrero-Bosagna. YouTube. Available at: https://www.youtube.com/watch?v=_aAhcNjmvhc.

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This article was prepared by Ulya Ammar (University of Edinburgh)

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