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Effect of obesity-associated gene variant on risk increases with birth year
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Adding another dimension to the conversation about the influence of genetics and environment on obesity, researchers said the year in which people are born plays a role in increased risk, according to findings published in the Proceedings of the National Academy of Sciences.
“Looking at participants in the Framingham Heart Study, we found that the correlation between the best known obesity-associated gene variant and BMI increased significantly as the year of birth of participants increased,” James Niels Rosenquist, MD, PhD, of Massachusetts General Hospital, said in a press release.
Rosenquist and colleagues from other institutions found the variant in the FTO gene previously linked to obesity risk demonstrated no correlation with obesity in participants born in earlier years and a much stronger correlation than reported for participants born in later years.
“These results, to our knowledge the first of their kind, suggest that this and perhaps other correlations between gene variants and physical traits may very significantly depending on when individuals were born, even for those born into the same families,” Rosenquist said in the release.
To explore whether the diverse environmental conditions experienced by different age groups may alter the effect of a gene variant, the researchers looked at data from participants in the Framingham Offspring Study, which follows children of participants in the original study. The data were collected between 1971, when participants were aged 27 to 63 years, and 2008.
Previous studies on interactions between genes and environment focused on differences within cohorts born during a specific time span, which would not account for changes in the larger environment occurring over time, the researchers said.
The investigators used constrained linear age-period-cohort models, including family controls, for a gene-by-environment analysis that examined interactions with contemporaneous environmental influences, as well as historical environmental influences. BMI was measured eight times during the study period.
Inherited FTO variants and birth year showed the previously reported association between a specific FTO variant and BMI occurred only in participants born in later years; no correlation was observed for those born before 1942, and the correlation was double that previously reported for participants born after 1942.
Environmental differences potentially combining with the FTO variant to increase obesity risk were not identified in the study. But the researchers speculated that reliance on technology rather than physical labor and availability of high-calorie processed foods are probable contributors.
“We know that environment plays a huge role in the expression of genes, and the fact that our effect can be seen even among siblings born during different years implies that global environmental factors, such as trends in food products and workplace activity, not just those found within families, may impact genetic traits,” Rosenquist said in the release.
“Our results underscore the importance of interpreting any genetic studies with a grain of salt and leave open the possibility that new genetic risk factors may be seen in the future due to different genetically driven responses to our ever-changing environment.”
Disclosure: The work was supported by a grant from the National Institute on Aging and the Social Sciences and Humanities Research Council. Funding for genotyping was provided by NHLBI, which supports The Framingham Heart Study in collaboration with Boston University.
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