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Aloha, people. The Doctor is in.

An interesting study just published in PLOS Medicine (Public Library of Science) has thrown some intriguing light on the old, old, oooollllllddd question of whether obesity is due to nature – what we would think of today as your genes – or nurture – your environment and how you behave in it.

Here’s the paper: http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001116

The vast group of researchers who worked on this research were interested in a particular gene, called the FTO gene. In 2007, a different group of researchers found that there is one allele for this gene (ie. a genetic variant) that about 16% of the population has, and, if you have that particular version of the FTO gene, then you are about 20% more likely to be obese than a person who has a different version of the gene.

That was big news in itself. Ever since the human genome was mapped, medical researchers have been trying to find specific genes that cause all kinds of health problems, obesity included. The first gene that was identified for obesity (the ob gene) was discovered in 1991 from studying an extremely fat breed of mouse – the poor things look like furry softballs with legs – which, because of its genetic make-up was unable to tell when it was full and so just kept eating constantly. Rather like Dr Then’s pet spaniel. [Whoo-hooo! Shout out for Bertie the spaniel!]

Now the ob gene, and the ten others like it which have been found to cause obesity are rare as rare as rare in the general population. Super rare. For example, there are only about five (human) families in the world who have been found to have the ob gene. And they’re weirdly inbred. No kidding. Dr Then likes an inbreeding joke as well as the next person, but in this case those ob families really are inbred. Cousins have been marrying cousins for a good few generations. They’ve probably only got one tooth between them.

So the point is – of those 11 genes that have been found to cause obesity, most are so rare that you’d never ever see them. Not so the FTO allele. That’s COMMON. 16% of the population. That’s like, of the 60 people who have looked at this blog to date, about 9 of them would have the FTO allele putting them at higher risk for obesity than the rest of you guys.

Well, here we are: as at 2007, we’d found the first commonly occurring gene for obesity. But wait on a second. The FTO allele doesn’t CAUSE obesity. It only increases risk of obesity. And what does ‘risk’ mean here? It means that if you got together a really big group of people with the FTO allele and another really big group of people without it, you’d find that about 32% of the people without the gene were obese compared with 38% of the people with the gene. (Big groups of Americans, that is. Other countries would have other (lower) figures, because their population rate of obesity is lower. I’m making life easy for me here with the calculations. Sue me.)

Amazing conclusion No 1:

You are not (necessarily) doomed by your genes. Since we’ve entered the genomic era (post the identification of DNA in 1953), we’ve developed the popular habit of thinking that

genes = FATE

Ok, so that’s true in some cases. (If, for example, you inherit a particular mutation of your Huntingtin gene, you are definitely getting Huntington’s disease. No doubt about it.) But for HEAPS and HEAPS of conditions, just having a gene or a particular version of a gene isn’t enough. Nearly 60 years of genetic research has shown that genetic disorders don’t all have the same ‘penetrance‘ (that’s the technical term, folks.) Some alleles, like the mutation of Huntingtin are completely penetrating (meaning, if you’ve got the allele, you’re getting the disease), while other alleles have a very low penetrance (meaning, you might have the allele, but it’s unlikely you’ll develop any symptoms.)

Why is this the case? We’re getting a bit off point here, people, but expect to be hearing a lot more about gene expression and epigenetics and multiple gene interactions in the next 60 years of gene research.

Anyhooo, to get back to the obesity bit, this common FTO variation has only middling penetrance. You might be genetically more susceptible to obesity if you have the variation, but you’re not doomed to fatness. Your genes may not fit, but your jeans will still fit.

And that latest study of the FTO variation found something even more interesting: people who had the obesity-associated FTO variation and who exercised lowered the risk of being obese. Exercise modified the effect of the gene.

Amazing conclusion No 2:

Behavior modifies gene effects.

Not only do genes not equal fate, but specific actions on your part can affect your susceptibility. Genes, environment and behavior all matter in causing obesity, as they do in so many instances of health.

Good stuff, huh? Well, I’m feeling nicely empowered for a Monday morning. I think I will chose to go and make a cup of tea now. And feed my spaniel.

Till next time, stay well,

Dr Then

Interested? Want more?

Here’s the orginal paper on the FTO gene’s affect on body weight:

Frayling T. M., Timpson N. J., et al. 2007, ‘A Common Variant in the FTO Gene Is Associated with Body Mass Index and Predisposes to Childhood and Adult Obesity’, Science, 316, 889-894. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646098/

On the ob mouse and the ob gene:

Friedman J. M., Leibel R. L., et al. 1991, ‘Molecular Mapping of the Mouse Ob Mutation’, Genomics, 11, 1054-1062.

Castracane V. D. and Henson M. C. 2006, ‘The Obese (Ob/Ob) Mouse and the Discovery of Leptin’, in Castracane V. D. (ed) Leptin, New York: Springer.

On the latest reckoning of obesity-associated genes:

Rankinen T., Zuberi A., et al. 2006, ‘The Human Obesity Gene Map: The 2005 Update’, Obesity, 14, 529-644.

One of the earliest rigorous studies testing the respective contributions of nature and nurture to obesity:

Garn S. M., Bailey S. M., et al. 1976, ‘Similarities between Parents and Their Adopted Children’, American Journal of Physical Anthropology, 45, 539-543.