Diet and Inheritance: You are what your grandparents ate

When we think of genetic inheritance, we tend to think of the DNA code being passed down from generation to generation, but you receive more from your ancestors than you think. Studies have found that you can also inherit the epigenome, the aspect of your genome beyond your DNA. The inheritance of epigenetic marks is called transgenerational epigenetic inheritance (TEI). Since epigenetics is the overlap between nature and nurture, environmental influences can affect the onset of disease throughout multiple generations. Diet is a major environmental factor that influences the functioning of the epigenome, and ancestral diet exposure may lead to diseases such as cardiovascular disease, obesity and fetal alcohol syndrome (FAS).  

One of the most notable examples of diet and nutrition influencing TEI comes from studying the epigenetics associated with the famine in Överkalix, Sweden. In this small city, detailed records were kept of the population and food supplies. Due to the extensive detail in these records, many studies have been able to link low food supplies during the pre-pubertal growth spurt of the grandparent generation to mortality and disease risk of the grandchild generation [1]. Many conclusions have been drawn from these studies that indicate sex-specific TEI. Cardiovascular-related mortality rates of males can be associated with the food accessibility in the paternal grandfather’s pre-puberty [2], and food accessibility of the grandmother during her pre-puberty stage determines the cardiovascular-related mortality of her granddaughters [1]. These studies also emphasise the importance of the age at which an individual is exposed to environmental influences will determine the TEI [1].

Additionally, with respect to the increasing prevalence of obesity, many studies have set out to investigate the effects of diet in relation to TEI and obesity. Raad et al. (2020) found that obesity is associated with Western diet and the paternal line. In a mouse study, maintaining a Western diet in males correlated to an increase in the body fat percentage and metabolic disease of the subsequent generations. The significance of the male influence on TEI is further emphasised by the experimental injection of sperm RNA into zygotes, which resulted in metabolic dysregulation [3]. Moreover, malnutrition, high-fat diets and environmental toxicant exposure of ancestral generation lead to DNA methylation, which  results in altered phenotypes of adipocyte metabolism and function. These epimutations (mutation in the expression of the gene, not the DNA sequence) are associated with the transgenerational inheritance of obesity [4].

Another area where diet may influence TEI is in FAS. This syndrome typically occurs due to mothers consuming alcohol while pregnant, and children present with physiological, neurobiological and cognitive deficits [5]. However, there is much research that shows a direct correlation between prenatal alcohol exposure, altered DNA methylation in maternal and paternal lines, and FAS. In a South African-based study on FAS, multiple imprinting control regions (ICRs) were analysed for altered DNA methylation patterns in relation to children with FAS. Two maternal ICRs (KvDMR1 and IG-DMR) were found to be significantly hypomethylated (a decrease in methylation marks), and PEG3 DMR was hypomethylated in paternal allele and is suspected to have major implications in the development of FAS [6]. This hypomethylation would correlate with the impact of alcohol in the one-carbon cycle.  Although there is much scope for further research on TEI and FAS, this study is a prime example of how lifestyle influences such as diet can have devastating effects on future generations. 

Although a significant portion of research on TEI has been aimed at understanding disease, there is no denying that TEI can also be influential from an evolutionary perspective. Epigenetics is the underlying mechanism in the development of phenotypes. Since the epigenome can be altered and inherited, TEI causes phenotypic plasticity and is therefore considered an evolutionary driving force [7].

TEI studies are expanding knowledge on the effects that epigenetics has in the inheritance and progression of disease. Improving our understanding will lead to the potential for decreasing disease in future generations and potentially lead to novel therapeutic approaches for treating these diseases. Educating the public on how lifestyle choices such as those relating to diet may affect their future descendants may be enough motivation for increased interest in healthier lifestyles. The effort to make better life choices could have major positive outcomes for the current generations while establishing a better quality of life for future generations [8]. 

Studies of TEI show the complexity with which inheritance, biological development and disease progression occur.  TEI blurs the line between nature and nurture, especially in the context of dietary influences. Dietary effects on the epigenome are transmitted through the germline (the sperm and eggs) and lead to the manifestation of disease in offspring. Future studies may show more evidence of how environmental factors influence the epigenome and influence the next generations. TEI emphasises that history will determine the future. The choices we currently make do not only affect us in  isolation but contain consequences for offspring. 

Let BioCertica’s DNA nutritional and welling kit help you to eat for the well-being of future generations. 

Written by: Jamie Fernandez, B.Sc Hons. in Genetics, Content Specialist

References 

[1] Pembrey, M., Saffery, R. and Bygren, L. O. lo. (2014) ‘Human transgenerational responses to early-life experience: potential impact on development, health and biomedical research’, Journal of medical genetics. BMJ Publishing Group, pp. 563–572. doi: 10.1136/jmedgenet-2014-102577.

[2] Vågerö, D. et al. (2018) ‘Paternal grandfather’s access to food predicts all-cause and cancer mortality in grandsons’, Nature Communications. Nature Publishing Group, 9(1), pp. 1–7. doi: 10.1038/s41467-018-07617-9.

[3] Raad, G. et al. (2020) ‘Paternal multigenerational exposure to an obesogenic diet drives epigenetic predisposition to metabolic disorders’, Obesity and Diabetes. Cold Spring Harbor Laboratory, (7), p. 2020.05.19.104075. doi: 10.1101/2020.05.19.104075.

[4] King, S. E. and Skinner, M. K. (2020) ‘Epigenetic Transgenerational Inheritance of Obesity Susceptibility’, Trends in Endocrinology and Metabolism. Elsevier Inc., pp. 478–494. doi: 10.1016/j.tem.2020.02.009.

[5] Lussier, A. A. et al. (2018) ‘DNA methylation as a predictor of fetal alcohol spectrum disorder’, Clinical Epigenetics. BioMed Central Ltd., 10(1), pp. 1–14. doi: 10.1186/s13148-018-0439-6.

[6] Masemola, M. L. et al. (2015) ‘Reduced DNA methylation at the PEG3 DMR and KvDMR1 loci in children exposed to alcohol in utero: A South African Fetal alcohol syndrome cohort study’, Frontiers in Genetics. Frontiers Media S.A., 6(MAR), p. 85. doi: 10.3389/fgene.2015.00085.

[7] Lind, M. I. and Spagopoulou, F. (2018) ‘Evolutionary consequences of epigenetic inheritance’, Heredity. Nature Publishing Group, pp. 205–209. doi: 10.1038/s41437-018-0113-y.

[8]Feil, R. and Fraga, M. F. (2012) ‘Epigenetics and the environment: Emerging patterns and implications’, Nature Reviews Genetics. Nature Publishing Group, pp. 97–109. doi: 10.1038/nrg3142.