Kids are full of surprises, right down to the coded biological programs they inherit, which may contain subtle chemical reminders of their parents' lifestyles. But if our parents' lifestyles are encoded in our biology, as some scientists speculate, then the way we think about health and lifestyle will change dramatically.
The general assumption is that our parents' lifestyles reach our genes only in the womb, through biochemical factors associated with maternal behavior during pregnancy. New research indicates, however, that we might actually inherit our fathers' lifestyles through a genetic mechanism that would come into play before the prenatal period.
The study, led by Duke University geneticist Adelheid Soubry, is the first to describe a correlation between a father's obesity prior to conception and changes in chemical marks on a gene known as IGF2 (insulin-like growth factor-2) in his offspring. The biological significance of the changes is as yet unclear, but the findings raise important questions about our inheritance of health.
The chemical “marks” Soubry and colleagues examined consist of methyl groups, which latch on to DNA in a process known as methylation. In animals, lifestyle factors such as diet can alter genes' methylation status, and in some cases those alterations have been found to stick, being passed from parent to offspring and even to generations beyond (see my previous post on transgenerational epigenetic inheritance for more detail).
The inheritance through generations of chemical, or epigenetic, modifications acquired during a parent's life before the conception of offspring offers an intriguing explanation for nature-nurture, or gene-environment, interactions. The prospect of its existence in humans is tantalizing, especially because of evidence that chemicals in our environments, including substances in food and household products, can alter gene expression without causing direct mutation in DNA. Those changes in gene expression might, in theory, increase our susceptibility to conditions such as diabetes or autism.
Epigenetic modification plays a key role in embryonic development by influencing the process of differentiation, in which cells are assigned gene expression profiles that guide their specialization, determining whether they become skin or muscle cells, for example. Modifications involved in development occur on imprinted genes, which come with parent-specific methylation marks. In a zygote (fertilized egg cell), those pre-existing modifications are erased and then established anew following sex determination. The zygote recreates the marks according to the inherited “epigenetic memory,” the program coded by the modifications in parental egg and sperm. The types of modifications that might be linked to lifestyle and acquired by the mother or father presumably become part of the epigenetic memory, or they might escape erasure altogether.
For humans, direct molecular evidence for the fetal uptake of epigenetic change, even from the mother, with whom the fetus shares an intimate environment, remains elusive. The most convincing proof is with a gene known as PPARGC1A, methylation of which in newborns has been linked to maternal body mass index, suggesting a potential role for methylation status in metabolic regulation.
Observational data, on the other hand, are more abundant, and they reveal compelling correlations. For example, in 2008 a team of scientists led by Columbia University epidemiologist L.H. Lumey reported that IGF2 methylation in adults who had been exposed prenatally to famine during the Dutch Hunger Winter of 1944–45 was reduced compared with methylation in younger or older siblings. Six decades later, those individuals who were exposed prenatally to famine were found to be at increased risk of insulin resistance, which frequently is associated with diabetes.
The Dutch Hunger research suggests that the health affects of changes in IGF2 methylation might not manifest in offspring for years. Unfortunately, that means that the impact of Soubry’s observations of obesity in fathers and IGF2 methylation in offspring probably won’t be known for some time.
We have plenty to mull over while we wait, however, including a commentary published alongside Soubry’s paper by University College London scientists Gudrun E. Moore and Philip Stanier. The commentary emphasizes the role of IGF2 as an imprinted gene.
Imprinted genes are atypical, and not only because they possess our epigenetic memory. Unlike most other genes, where we inherit two working copies (one from each parent), we carry only a single functional copy of each imprinted gene. In the case of IGF2, we inherit the functional copy from the father, while methylation renders the mother's copy inactive.
Lumey’s and Soubry’s studies suggest that maternal famine and paternal obesity are both linked to decreased IGF2 methylation. However, maternal famine during the Dutch Hunger likely also coincided with paternal famine, and Soubry and colleagues, Moore, and Stanier speculate that undernutrition in the father, too, may be associated with the gene’s reduced methylation. No one has actually investigated that association, but if this is true, then the relationship between a father’s nutrition prior to conception and IGF2 methylation in his children may be even more complicated.
Deciphering the nuances is critical, because whether famine- or obesity-related, any supposed inherited change in IGF2 methylation raises concern about the possibility of long-term health consequences. Cancer and other chronic diseases have been associated with similar alterations in IGF2 methylation.
While the science is complex, the solution may be simple, if we consider this simple observation: kids adopt their parents' behaviors, for better or worse. If we want the legacy of our lifestyles to be a healthy one, we need to lead by example, and that takes practice, initiated well before our little ones come along.