Disentangling nature and nurture just got more complicated. Now it seems that time, too, may be involved in gene/environment interactions, say scientists who evaluated the effects of a gene variant long associated with obesity risk. The variant, which affects the FTO gene, appears to have more or less impact depending on a person’s year of birth.

The FTO variant has the greatest impact on body mass index (BMI) for those born after 1942. In fact, the impact was found to be twice as strong as reported in previous studies, which were confined to less wide-ranging age cohorts than the current study, which delved into information collected by the Framingham Offspring Study, an offshoot of a project that began gathering data in 1971. In contrast, the impact of the FTO variant was found to be essentially nil among study participants who were born before 1942.

These results appeared December 29 in the early edition of the Proceedings of the National Academy of Sciences, in an article entitled, “Cohort of birth modifies the association between FTO genotype and BMI.” In this article, the authors noted that varied cohort and period effects—such as birth cohort, time period, and the lifecycle—integrate many potential environmental factors. So, to evaluate gene/environment interactions, the authors took into account both time-varying contemporaneous and historical environmental influences.

“Using constrained linear age–period–cohort models that include family controls, we find that there is a robust relationship between birth cohort and the genotype–phenotype correlation between the FTO risk allele and BMI, with an observed inflection point for those born after 1942,” wrote the authors. “These results suggest genetic influences on complex traits like obesity can vary over time, presumably because of global environmental changes that modify allelic penetrance.”

The study’s authors represent several institutions including Yale University and Massachusetts General Hospital. One co-author, Nicholas Christakis, M.D., Ph.D., a Yale professor sociology, ecology and evolutionary biology, and medicine, said that the study suggests that even more caution and humility in modern genetics research is warranted. “It also,” he continued, “suggests that if large-scale genetic association studies with this gene had been conducted a generation earlier, they could have had different results.”

“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,” explained another study co-author, James Niels Rosenquist, M.D., Ph.D., a psychiatrist at Massachusetts General Hospital. “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.”

As scientists probe further into gene-by-birth-cohort and gene-by-environment interactions, Drs. Rosenquist and Christakis said it ultimately may be important for researchers to choose broad populations from many types of environments when studying the ways genes are expressed.

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