The FTO gene

We watched the BBC Horizon programme on genetic causes of obesity, fronted by Dr Giles Yeo (good to see an ethnic East Asian presenter).

Dr Giles Yeo with some of the AA variant folk

There is a gene of quite large effect; here is what Wikipedia says:

"A study of 38,759 Europeans for variants of FTO identified an obesity risk allele. In particular, carriers of one copy of the allele weighed on average 1.2 kilograms (2.6 lb) more than people with no copies.

"Carriers of two copies (16% of the subjects) weighed 3 kilograms (6.6 lb) more and had a 1.67-fold higher rate of obesity than those with no copies.

"The association was observed in ages 7 and upwards. "

...

"In adult humans, it was shown that adults bearing the at risk AT and AA alleles at rs9939609 consumed between 500 and 1250 kJ more each day than those carrying the protective TT genotype (equivalent to between 125 and 280 kcal per day more intake).

"The same study showed that there was no impact of the polymorphism on energy expenditure. This finding of an effect of the rs9939609 polymorphism on food intake or satiety has been independently replicated in five subsequent studies (in order of publication)."

The protective allele is T while the risk allele is A at SNP site rs9939609.

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Here is what 23andMe says about my late mother, Beryl Seel, and myself.

My mother had the protective genotype, TT, and was never overweight; I'm not so lucky (AT) and had to fight to get my weight down to its current 70-71 kilograms (from 86kg in mid-2012).

We can infer that my late father, who definitely had an expanded waistline, was AT or AA. Based on family history and if pressed, I would guess AT .. and that I got unlucky.

I wrote about this 18 months ago: another Horizon programme.

Obesity genes and me

The BBC science programme Horizon is currently running a three part series on the science of dieting. They have identified three categories of the obese and one - the 'constant cravers' - are defined by having 'obesity genes'.

It seems likely that I'm a 'constant craver'.

A little internet research provides a short list.

1. The FTO gene

As Wikipedia explains: "In 2009 variants in the FTO gene were further confirmed to associate with obesity in two very large genome-wide association studies of body mass index (BMI). It was shown that adults bearing the at-risk AT and AA alleles at rs9939609 consumed between 125 and 280 Calories per day than those carrying the protective TT genotype," (c. 5-12% of the daily allowance).

A quick search for rs9939609 confirms I'm AT at this location. No wonder I was thirteen and a half stone before starting the 5:2 diet (I'm now at 11 stone = 70 kg but not without continuing maintenance). As a carrier of one of the 'A' risk alleles my disposition to obesity is 30% higher than that of baseline TT people.

2. The MC4R gene

"Mutations in the MC4R gene account for 6-8% of obesity cases. A common variant of the MC4R gene, distributed in about 22% of the population, increases the risk for weight gain by causing increased appetite and decreased satiety. Calorie restriction through portion control and smart food choices is the best strategy for weight loss for people carrying this variant."

The relevant SNP is rs17782313 where C alleles are associated with higher body mass index (BMI). The three options are CC, CT, TT - where TT is baseline normal, CT is associated with a BMI increase of 0.22 units and CC with a BMI increase of 0.44 units. As is so often the case, the allele effects are, as you see, additive.

What am I?  Yep, it's bad: CC.

3  The ADIPOQ gene

The relevant allele is rs17366568. "A significant genotypic association was observed between ADIPOQ rs17366568 and obesity. The frequencies of AG and AA genotypes were significantly higher in the obese group (11%) than in the non-obese group (5%) (P=0.024). The odds of A alleles occurring among the obese group were twice those among the non-obese group (odds ratio 2.15; 95% confidence interval 1.13-4.09)." (From here).

At last some good news! I am GG at this location.

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Doubtlessly I'll return to this topic when more is known, especially as the results to-date are so personally depressing!