Making sense of obesity genes

This is a quick follow-up to my other post on fat cells, which as it happens, isn't the only obesity-related story out today. Another paper found a common genetic variant that increases the risk of obesity in its carriers.

A huge team of researchers scoured the genomes of almost 17,000 European people for genetic variations that are linked to obesity. Until now, only one has been found and it sits within a gene called FTO. This new study confirmed that FTO variants have the strongest association with obesity, but in the runner-up position is another variant near a gene called melanocortin-4 receptor or MC4R.

Given that this new variant isn't actually within the gene itself, it most likely affects the risk of obesity by changing how MC4R is controlled. This isn't the first time that MC4R has been linked to obesity. It's involved in controlling appetite and metabolism, and people with rarer mutations in the gene itself become severely obese at an early age. The new variant has much less dramatic effects, but it's also much more common. In fact, 81% of people carry at least one risky variant at either FTO or MC4R.

Despite their widespread nature, the effects of these risky variants are very modest and their location can only be revealed by very large collaborative studies like this one. For example, each copy of the new MC4R-associated variant typically increases a person's BMI by a mere 0.2 units, although the researchers found that each copy also increases the risk of being severely obese by 31%. It's almost certain that a whole slew of variants like these influence the large variations in bodyweight in modern populations.

Whenever an obesity-related gene or variant is identified, the reactions from both the press and the public are often more interesting than the results themselves. I've written about this in a previous post on FTO, and since many of the same lessons are applicable to this new study, I'm going to partially repost what I wrote at the time.

To many people, the discovery of an "obesity gene" is yet another way for obese people to brush off the burden of responsibility from their shoulders. After all, they say, obesity is just a matter of eating healthily and exercising regularly. To go beyond this is to over-complicate a simple lack of willpower. And where exactly was this gene in post-war Britain when obesity levels were much lower?

This attitude couldn't be more wrong or more unhelpful, and many of these complaints misunderstand the nature of obesity-related genes. It is clear that obesity has some genetic basis, but no researcher worth their salt would imagine that a single gene dictates whether a person becomes obese or not. Obesity-related genes are likely to work through much more delicate ways, by affecting our metabolism or the way we lay down fat.

But subtlest of all are genes that affect our very behaviour. These inherited influences could make individuals more responsive to the smells or sights of food. They could make the brain less responsive to signals from the gut that say, "I'm full." They could give people a strong innate preference for the chemicals that give fatty foods their taste.

These subtle effects only become apparent when food is plentiful. When supplies are more modest,  say post-war Britain, variations in such genes across a population wouldn't have much effect. But in the 21st century, a combo of widely available, cheap junk food and sedentary jobs or pastimes make it easy to eat lots and do little. In this environment, small genetic differences that affect how people react to food or activity can have massive effects.

This is a case of nature via nurture; of genes and environment interacting with each other to affect our behaviour. Obese people are likely to carry around a large range of genetic variants that alter their behaviour in ways that leave them very vulnerable in a world where obesity is just around the corner.

Obesity then, is a complex disease with many underlying causes, some of which are genetic. And because of this, throwing words like 'self-discipline' and 'laziness' about with cavalier abandon does nothing for the obesity debate or for obese people themselves.

Is the combination of genes and environment an excuse for obesity? Hardly. But it does go some way toward explaining it, which is more than an accusation of faulty willpower will do. Scientists hope that understanding the genetics of obesity may herald new treatments, but this is a hope for the future. For the present, very little actually changes for obese and overweight people.

To overcome the effects of genes and environment, they must still make lifestyle choices. The old maxim of "eat well, be active" still applies. The real benefit of these discoveries would be a change in the attitudes of everyone else, from damning to supportive and from accusatory to understanding.

Now enough lecturing, here's a little game. I'm writing this post before the story's embargo breaks and at this minute, other journalists are probably doing the same thing. The story may not get covered at all but if it is, there's a very good chance that the medley of headlines will betray a fundamental misunderstanding of the nature of genetics. So, let's play a headline bingo. If the story does make it into tomorrow's papers, see if you can spot any of the following phrases:

• Obesity being described as "in the genes"
• "The gene that makes you fat" or anything equally deterministic
• "Scientists discover fat gene" or anything suggesting this is the first time this has happened
• Any use of "It's official!" or "Proof" or anything that suggests that replication is for wusses

Reference: Loos, R.J., et al. (2008). Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nature Genetics DOI: 10.1038/ng.140