GeneBites

Is your risk for a disease because of your ancestry or because of where you grew up and how you were raised? By comparing siblings, researchers separated the effects of these two factors for residents in Mexico City.

Nature vs. Nurture: the age-old genetics argument. Which traits come from your ancestry, and which come from the environment you live in? Geneticists have determined that traits such as eye colour, skin tone and blood type come largely from nature, or ancestry. Others can be caused by location, food you eat and the pollutants you’ve been exposed to. However, quantifying the contribution of ancestry and environmental factors for metabolism and risk for diseases such as Type 2 diabetes is a bit more difficult to parse.

This is exactly the problem scientists are trying to solve! How do we tease apart these two important factors that play a role in determining phenotypes, or how genetic code manifests in an individual’s observable traits? One way to go about this question is to analyze the genome of individuals to identify similarities and differences. This process allows scientists to compare different ancestries (Indigenous American, European, African, etc.) to see if genomic patterns are more present in some rather than others, and how these correlate with phenotypes. Despite this, it still does not account for the environmental differences that may arise between different families and communities.

In a recent study, researchers were able to further break down the difference in contribution between ancestry and environmental factors in a cohort of people in Mexico City. In addition to showing population differences, they were able to compare the genomic information of nearly 40,000 relatives in more than 17,000 families. Siblings share most of their environment, but they differ slightly in ancestry by chance. That means differences between siblings are more likely to reflect genetics than upbringing. Scientists can assume minimal environmental factors because siblings commonly have shared socioeconomic statuses, parental practices, diets and exposures to toxins/pathogens. Imagine two parents who each carry a mix of Indigenous American and European ancestry. Because each child inherits a random half of each parent’s DNA, one child might end up with 62% Indigenous American ancestry and their sibling with 59%. The siblings grew up in the same home, ate similar food, and shared the same family income. So if, across thousands of families, the sibling with slightly more Indigenous American ancestry tends to be shorter or more likely to develop diabetes, that points to genetics rather than environment.

The study focused on finding families with mixed ancestry to identify phenotypic differences with genomic differences. Among the key findings when comparing populations across ancestries (without accounting for families) was that people with more Indigenous American ancestry tended to be shorter than those with more European ancestry. Additionally, it was found that Type 2 diabetes was more common in people with more Indigenous American ancestry. When looking at family-specific genomic differences, the link between Indigenous American ancestry and diabetes held up even when comparing siblings, as did the link with height, suggesting a genetic contribution to both. Notably, every trait followed this pattern. Educational attainment was strongly linked to ancestry across the whole population, yet that link disappeared when comparing siblings. This suggests the education gap is driven by environmental and social factors, not genetics. Even for diabetes and height, the authors caution that a genetic link doesn’t reveal the mechanism. For example, siblings with different ancestry may differ in skin tone and be treated differently by society.

This study highlights a key issue in the field of population health analysis: we must critically evaluate significant differences between two groups. Is this indicating causation or just correlation? The way we go about this analysis can provide us more insight into what contributes to Nature vs. Nurture. This study focuses on Mexico City residents, but what other things can we discover in other populations and cities?

Edited by Zach Patterson and JP Flores

Cover photo (courtesy of Pexels): https://www.pexels.com/photo/celebration-at-angel-of-independence-38597266/