Those who carry a particular obesity-related gene variant are more likely to be overweight. Yet, a new study shows that this same gene variant might not have predisposed previous generations to obesity if they were born before 1942.
Analyzing data collected between 1971 and 2008 from over 3,000 subjects making up the offspring cohort of the Framingham Heart Study, researchers confirmed the link between the gene — known as FTO — and body mass index. People with a single copy of this allele had a BMI that was on average 0.5 units higher, corresponding to a 3-pound increase for the average adult. However, this correlation disappeared in subjects born before 1942, highlighting how the effects of our genes can change over time.
“Our work shows that genetics is historically contingent,” said Nicholas Christakis ’84, professor of social and natural science at Yale and senior author of the paper.
The era in which subjects are born or in which scientists do their work could affect the significance of genetic influences, he explained. If investigators had studied the effect of the FTO gene on obesity 40 years ago, they might have wrongly concluded that there was no relationship.
It is not surprising that the genetic association differs between cohorts socialized in two very different environments, said Jason Boardman, director of the Health and Society Program at University of Colorado Boulder, a researcher who was not involved in this study. Still, Boardman said that these findings are important for researchers and policy makers because they mark the pitfalls of generalizing from one cohort to the next.
“Policies that were effective in changing health behaviors in one generation may not be particularly effective in successive generations,” he said. A different interplay of genetic and environmental factors may be responsible for obesity today, he added.
Previous studies only focused on how a specific environmental factor influenced genetic effects, and were furthermore limited to a narrow time period, said Niels Rosenquist, psychiatrist at the Massachusetts General Hospital and lead author of the study.
The interdisciplinary nature of this team — comprising experts in psychiatry, health policy, economics, genetics and sociology — was its strength, Rosenquist said. It enabled the researchers to make sense of the longitudinal data that was available thanks to the unique nature of the Framingham Heart Study. The Framingham Heart Study started in 1948 and is now on its third generation of participants.
“We brought certain methods to genetics that a lot of population geneticists don’t work with,” Rosenquist said. These mathematical tools, more typically used in social science, allowed the team to disentangle the effects that different factors have on obesity, Christakis added.
The specific environmental changes between the 1940s and today that are responsible for the change, however, are yet to be identified. Studies linking environmental changes in particular regions to changes in gene-environment associations in these regions would help pin down these factors, the authors suggest.
This work exemplifies how social and biological factors are in conversation with each other, said Christakis, an interplay that he will be exploring in his class “Health of the Public” this semester. Biology can play a role in culture, guiding our behavior and the social decisions we make; conversely, social experience and culture can play a role in biology, Christakis explained.
The FTO risk allele is relatively common in the human population, with 65 percent of the study’s participants carrying at least one copy.