Can Your Genes Make You Fat?

Your genes can make you fat – but only if you’re born after 1942. That seems like a nonsensical statement, but it’s the conclusion of a thought-provoking study in the Proceedings of the National Academy of Sciences that tracked BMI and genetic markers in participants in the famous Framingham Heart Study.

There’s a particular variant of a gene called FTO that is associated with higher BMI, but its effects are only apparent in the people born since 1942. Presumably changes in environmental factors – e.g. the cost and type of food available – have disproportionately affected people with certain genetic risk factors. (The FTO variant is thought to be associated with food intake, not energy expenditure.)

So what does this mean for public health? I explore this question in my Globe and Mail column this week:

[…] But the change in FTO’s apparent power isn’t likely an isolated case, says Dr. James Niels Rosenquist, 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, co-author of the FTO paper, plans to present some of those results at a 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 explains. 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 person 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. 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 FTO study also got a mention in Michael Joyner’s New York Times article last week. He argues that the promise of genetically targeted medicine has been overstated for reasons that have a lot to do with the findings of this FTO study:

[…] The basic idea behind it is that we each have genetic variants that put us at increased or decreased risk of getting various diseases, or that make us more or less responsive to specific treatments. If we can read someone’s genetic code, then we should be able to provide him or her with more effective therapeutic and preventive strategies.

But for most common diseases, hundreds of genetic risk variants with small effects have been identified, and it is hard to develop a clear picture of who is really at risk for what. This was actually one of the major and unexpected findings of the Human Genome Project. In the 1990s and early 2000s, it was thought that a few genetic variants would be found to account for a lot of disease risk. But for widespread diseases like diabetes, heart disease and most cancers, no clear genetic story has emerged for a vast majority of cases.

Age, sex, body weight and a few simple blood tests are much better predictors of Type 2 diabetes, for example, than a genetic score based on how many snippets of “risky” DNA you have. And the advice for those at risk to exercise more and eat more healthfully remains the same. […]

That last point is a crucial one, I think. Even if we do acquire the ability to give accurate genetic risk assessments – a big if – what are we going to do with the information? If the advice is to exercise more and eat healthily, how is that different from the advice everyone is already getting? The real question is why we have so much trouble obeying this advice. As Joyner concludes:

We would be better off directing more resources to understanding what it takes to solve messy problems about how humans behave as individuals and in groups. Ultimately, we almost certainly have more control over how much we exercise, eat, drink and smoke than we do over our genomes.

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