Obesity as part of normal human variation

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Common body mass index-associated variants confer risk of extreme obesity:

To investigate the genetic architecture of severe obesity, we performed a genome-wide association study of 775 cases and 3197 unascertained controls at 550 000 markers across the autosomal genome. We found convincing association to the previously described locus including the FTO gene. We also found evidence of association at a further six of 12 other loci previously reported to influence body mass index (BMI) in the general population and one of three associations to severe childhood and adult obesity and that cases have a higher proportion of risk-conferring alleles than controls. We found no evidence of homozygosity at any locus due to identity-by-descent associating with phenotype which would be indicative of rare, penetrant alleles, nor was there excess genome-wide homozygosity in cases relative to controls. Our results suggest that variants influencing BMI also contribute to severe obesity, a condition at the extreme of the phenotypic spectrum rather than a distinct condition.

As I'm sure you know, some traits, like pigmentation, are controlled by variation on a few genes, a half a dozen. For example, one locus, SLC24A5 controls 25-40% of the complexion variation between Europeans and Africans, and can account for he same proportion of complexion variation among South Asians. By contrast, variation in height is explained by genes of much smaller effect, excepting distinct phenotypes such as dwarfism.

These data reiterate that though genes such as FTO are of particular interest in relation to variation in body mass index should probably be viewed as a quantitative trait, whereby the obese are simply at the "tail" of the distribution which emerges in response to a particular environment. This is what I mean (these are not real distributions!):

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As you can see, simply changing the environment will result in an increase in the number who are defined as obese (BMI >= 30) as the tail of the distribution moves to the right....

Cite: Human Molecular Genetics 2009 18(18):3502-3507; doi:10.1093/hmg/ddp292

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Hilarious photo. Good thing you added those black bars. You wouldn't want readers to be distracted by those feminine features!

Thanks Razib that's almost exactly what I was trying to get my head around when you reported Cosgrove's remark earlier "We should declare obesity a disease and say we're going to help you get over it". The cause of an individual's obesity may or may not be medical, but trying to address the increasing numbers in this way is medicalising what is essentially an environmental issue.

Why on earth would you put black bars on the terra cotta? Do you feel some of the culturally conservative muslim environment you were raised in retaining a hold on you?

If looking at millennial old terra cotta figurines depicting exaggerated representation of female sexual organs due to ritualistic worship of the feminine gets you fired, you probably shouldn't be working there in the first place, because it is run by nutjobs.

By KarenElhyam (not verified) on 21 Aug 2009 #permalink

this is dumb. 2,000 ppl read this blog every day. it wasn't done for my sake. i also thought it would be funny.

How bout the Yanomamo, who apparently lived a stably non-malthusian life because of their florid warfare over women. With malthusian limitation absent, shouldn't they evolve to have quite modest levels of hunger, and be little disposed to overeating? Do they get fat when living the modern life?

Likewise, if their diets are already replete, wouldn't they have the same adult heights as their ancestors, even if raised in an affluent modern lifestyle?

By Eric Johnson (not verified) on 21 Aug 2009 #permalink

> i also thought it would be funny

It is for sure, yet "work-safety" strikes me as bewildering consideration. Is it the Euro in me? The few who might get in trouble may safely be trusted to scroll past the picture, else, they may read it when the talib next desk is busy in the outhouse or the multi-confessional prayer facility, whichever comes first.

mohling, sexual harassment issues are probably more relevant in the US when it comes to these sorts of pictures.

> sexual harassment issues are probably more
> relevant in the US

Yes, the talibas are a nuisance, too. We're on a good way, though, with the usual 10-15 years of cultural delay. And why shouldn't we have some fun as well.