What your genes can tell you about your health

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Yes, your genes can make you fat – but only, according to a new analysis, if you were born after 1942.

That may sound like an odd statement, but it reflects a growing realization that the links between genes and health are more nuanced than previously thought. Nature and nurture always interact, but these days society is changing so rapidly that particular genes may well have completely different effects from one generation to the next. That makes things more complicated, but it's actually good news: When it comes to health, rumours of genetic predestination have been greatly exaggerated.

The new study, published last month in the Proceedings of the National Academy of Sciences, tracked 3,760 subjects in the Framingham Offspring Study, an offshoot of the famously long-running Framingham Heart Study, between 1971 and 2008. During that period, the subjects were weighed eight times and underwent genetic testing to identify those with a particular variant of a gene most commonly called FTO, which has been associated with higher risk of obesity.

Sure enough, those with the FTO variant tended to have higher body-mass index. But the effect was most pronounced for those born later; in fact, there was no relationship at all between FTO status and BMI for those born before 1942, while the correlation was twice as strong as previously reported for those born after 1942. If genes are fate, then fate is apparently getting stronger – and that suggests there's something else going on.

The study, by a group of researchers at Harvard, Queen's, Dartmouth and Yale universities, can't pinpoint the exact changes that are making the effects of FTO more apparent. There are lots of theories about what societal changes are making us fatter, but previous research suggests FTO is linked to food intake and appetite, rather than to levels of physical activity. It may be that the rise of cheap, heavily processed food laced with hard-to-resist sugar and salt is hitting those with the FTO variant harder than the rest of us.

But the change in FTO's apparent power isn't likely an isolated case, says Dr. James Niels Rosenquist of Harvard and Massachusetts General Hospital, the study's lead author. FTO is easy to study because it has such a strong effect, but "there are a number of genetic variants whose effects appear to be mediated by the environment," he says.

In fact, the researchers are following up with further analyses of the same data set related to another obesity-related gene, MCR4, and two smoking-related genes, CHRN3 and CHRN5. Dr. Steven Lehrer, a professor in Queen's University's economics department and School of Policy Studies and a co-author of the FTO paper, plans to present some of those results at a Health Canada conference later this month.

"The punchline of the talk is that the genetic distribution of those with disorders has been shifting over time to those most vulnerable by genetic predisposition," he explained in an e-mail. In other words, people who are obese, addicted to smoking or struggling with other conditions such as substance abuse or compulsive gambling are increasingly likely to be those with genes that predispose them to these problems. Moreover, Lehrer adds, "many of the policies we introduce are [unknowingly] playing a role."

For example, he says, "sin taxes" and other measures that target individual incentives may work well to dissuade the average Canadian from smoking or gambling, but don't dissuade those who are most susceptible. The same would be true of a sugar tax or soda tax, such as the one passed last year in Berkeley, Calif. So the question that public-health researchers and policy makers now need to wrestle with is how to shift behaviour among the most genetically vulnerable.

The findings are likely to apply to many other genetic contributions to health, too. The phenomenon of "exercise resistance" has garnered considerable attention over the past few years, thanks to studies showing widely varying responses when a group of people do an identical exercise program. About 15 to 20 per cent of people fail to make any improvements at all in their metabolic health following prolonged exercise regimens, and these non-responders share certain genetic variants.

But labelling exercise resistance as a genetic problem makes it sound like this fate is predetermined and unavoidable – as if, independent of all other considerations, 15 to 20 per cent of all humans are simply immune to exercise. What Rosenquist and Lehrer's results tell us, instead, are that such results are simply a snapshot of one particular group at one particular place and time. If we can figure out what environmental factors are making people more exercise-resistant, we can change those factors.

So what changes are relevant? In a paper published last month in the Journal of Clinical Endocrinology & Metabolism, researchers from the Sanford-Burnham Medical Research Institute in Florida argued that exercise resistance may depend on epigenetic as well as genetic mechanisms. These are markers that determine which genes are turned on or off – and, unlike genes, they can be altered by environmental cues like diet and exercise.

Though the research remains preliminary, the implication is that someone who seems exercise-resistant after three months of exercise might respond differently, thanks to gradual epigenetic changes, after a year or two of regular exercise.

Put it all together, and you're left with a very muddy picture of what our genes actually tell us about health. In fact, points out Dr. Michael Joyner, a physiologist at the Mayo Clinic in Minnesota, the very definition of "gene" is up in the air. "It used to have a pretty clear meaning, and now essentially no one knows," he says.

Research such as the new FTO study highlights the shift, he adds. The simple view that each gene corresponds to a trait you either do or don't have is no longer meaningful. For example, height has been linked to more than 180 different genetic sites, none of which exert more than a minor effect on its own. Instead, Joyner says, genes play a role that is "context-specific and highly dependent on culture, environment and behaviour."

None of this is to say that genes are irrelevant, or that genetic research isn't useful. Even if it wasn't true in 1942, it's now true that the version of the FTO gene you possess affects your probability of being overweight. That doesn't mean that genes are destiny; it means that those affected – or perhaps all of us – should try to live, in certain key ways that still need to be determined, like it's 1942.

Alex Hutchinson blogs about exercise research at sweatscience.runnersworld.com. His latest book is Which Comes First, Cardio or Weights?