Genetic Effect on Obesity Increases with Obesogenic Environment

Imagine that there were people with a genetic predisposition to asthma. Many different genes are involved – the more ‘asthma’ genes you have – the more severe your asthma.

Now imagine that people with a high genetic risk, a moderate genetic risk, a substantial genetic risk and a severe genetic risk for asthma were all living out in cottage country, where there is clean air with no air-borne dust or pollutants. Only those few individuals unfortunate enough to have ‘severe’ genetic risk would have asthma – everyone else would be perfectly fine.

Researchers studying the relationship between asthma and genetics in cottage country would find that in most people genes have no effect on asthma symptoms and only in people with very severe asthma would there appear to be some genetic influence.

Now imagine that a busy highway is built straight through that community with lots of heavy car and truck traffic that significantly reduces air quality.

Now, even those with low genetic risk will start wheezing, those with moderate risk will start coughing, those with substantial risk will no longer be able to do heavy work outside, and those with the most severe risk will be confined to their beds under an oxygen tent.

Suddenly, researchers studying this community, will find that there is a close relationship between genetic risk and asthma symptoms – indeed, the difference between those who have no, some, moderate, substantial or severe asthma can almost entirely be explained by genetics. In fact, in those with any symptom of asthma – the entire ‘variance’ will be found to be almost completely attributable to their genetic risk – suddenly genes become the most important determinant of who has symptoms and who doesn’t!

Not surprisingly, exactly the same is true with obesity, according to a large twin study by Benjamin Rokholm and colleagues from the University of Copenhagen, published in the latest edition of PLoS One.

The researchers examined data on 15,017 monozygotic and dizygotic twin pairs born between 1931 through 1982.

Using classical twin-study methodologies, they found that the additive genetic variation was positively and significantly associated with obesity prevalence and the mean of the BMI distribution.

In other words, as the prevalence of obesity, prevalence of overweight and the BMI mean increased, so did the ‘genetic’ variation in BMI.

As in the theoretical asthma example, these findings are consistent with the notion that variations in genes related to body fatness are more important and lead to greater weight gain under the influence of an obesity-promoting environment.

While this study points to the idea that we need to get serious about tackling the environmental drivers of obesity, it also means that in the meantime, the existing environmental factors will disproportionately affect those with the greatest genetic risk.

So, while everyone is sedentary, get too little sleep, is stressed out and, therefore, eats too many calories – those with the greatest genetic load will gain the most weight, while those with no genetic risk will be just fine (we all know these people).

From a health services perspective this means that, while we wait for policy makers to pass new laws that will help reverse the many obesogenic factors in our current environment (which is likely to take as long as it will take them to reverse global warming), we need to provide appropriate help and care to those who are suffering the consequences from having chosen the wrong parents.

Genetics does not mean you cannot do anything about it – it just means that those with a greater genetic risk need to do much more (often with professional help) to manage their weight than those who happen to have lower genetic risk.

Of course it is also not helpful to tell those with the highest genetic risk to simply live like those with no genetic risk – because that is already exactly what they are doing – unfortunately, they have to do far more!

Sure, the best way to get our severe asthma patient out of the oxygen tent would be to shut down the highway (or mandate cleaner cars) – in the meantime, however, let’s make sure there’s enough oxygen flowing into the tent for those who need it.

AMS
Edmonton, Alberta

Rokholm B, Silventoinen K, Angquist L, Skytthe A, Kyvik KO, & Sørensen TI (2011). Increased Genetic Variance of BMI with a Higher Prevalence of Obesity. PloS one, 6 (6) PMID: 21738588