Obesity Gene Didn't Influence Body Mass Index Until 1942

Miriam E Tucker

January 05, 2015

The documented association between a particular gene variant and body mass index (BMI) apparently dates back only to the World War II era, suggesting that environmental changes could influence the way genes are expressed, a new study finds.

The results were published online December 29, 2014 in the Proceedings of the National Academy of Sciences by Dr James Niels Rosenquist (Harvard University and the Massachusetts General Hospital Department of Psychiatry, Boston) and colleagues.

"Genetics only begin to tell the story. It's important, but there are all these other factors that come into play," Dr Rosenquist told Medscape Medical News.

The investigators used data from the Framingham Heart Study, which began enrolling 5209 people in 1948, and the subsequent Framingham Offspring Study, which enrolled 5124 of the original cohort's offspring beginning in 1971, when the offspring ranged in age from their teens to their 50s. Only data taken when the subjects were aged 27 to 63 (through 2008) were used, in order to limit the effects of age per se.

Using various models, Dr Rosenquist and colleagues found a strong association between the rs993609 variant of the FTO (fat-mass– and obesity-associated) gene and BMI from 1942–1945 onward, but not prior to that time. Although the study did not look at environmental mediators, the 1940s were about the time when technological advances began reducing energy expenditure and high-calorie processed foods became prevalent, they note in the paper.

Dr Rosenquist told Medscape Medical News that this study is the first to add the dimension of time to the exploration of genotype-environment influences on phenotype. Most previous studies have been cross-sectional and have yielded mixed results.

"Since the discovery of the human genome structure, there has been a tremendous amount of interest in linking various genes with what happens next....Instead of focusing on specific environmental factors, we looked at whether the epoch you were born in had an impact on whether or not these genes [had] a strong significance," he explained.

The study showed that even among siblings, those born later with the variant of the FTO gene — believed to play a role in appetite and satiety — had higher BMIs. "That's important, because people think family risk is immutable. This paper is a small step but starts to question whether that's the case," Dr Rosenquist said.

Physicians can point to these data in counseling patients about the limitations of genetic tests such as those that were offered by the start-up company 23andMe before the Food and Drug Administration halted them but that could make a comeback. "This study is further evidence to arm the clinician to explain that a test result doesn't mean you are X percent more likely to get something," Dr Rosenquist told Medscape Medical News.

The findings also could help to further the development of personalized medicine and enhance the ability to predict risk. "If you're able to parse out when and where these things have an effect, you can do a much more accurate job of identifying individual risk and susceptibility to medications....The finding suggests it's not just who you are, but where and when."

Dr Rosenquist and coauthors have reported they have no relevant financial relationships.

Proc Natl Acad Sci USA. Published December 29, 2014. Abstract

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