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 which can be cross-correlated with my 23andMe genotype download.

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 of my Excel spreadsheet 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.

---

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

MAO-A: violence through to depression

From BBC News today:

"A genetic analysis of almost 900 offenders in Finland has revealed two genes associated with violent crime. Those with the genes were 13 times more likely to have a history of repeated violent behaviour. The authors of the study, published in the journal Molecular Psychiatry, said at least 5-10% of all violent crime in Finland could be attributed to individuals with these genotypes.
...
"Each criminal was given a profile based on their offences, categorising them into violent or non-violent. The association between genes and previous behaviour was strongest for the 78 who fitted the "extremely violent offender" profile. This group had committed a total of 1,154 murders, manslaughters, attempted homicides or batteries. A replication group of 114 criminals had all committed at least one murder. These all carried a low-activity version of the MAO-A gene, which previous research has dubbed the "warrior gene" because of its link to aggressive behaviour."

Monoamine oxidase A, also known as MAO-A, is an enzyme encoded by the MAO-A gene. It operates in nerve tissue where it degrades neurotransmitters such as dopamine, norepinephrine, and serotonin. This affects mood.

This "warrior gene" thing is somewhat old news. Wikipedia states (in a rather badly-written article):

"In humans, there is a 30-base repeat sequence repeated in one of several different numbers of times in the promoter region of the gene coding for MAO-A. There are 2R (two repeats), 3R, 3.5R, 4R, and 5R variants of the repeat sequence, with the 3R and 4R variants most common in Caucasians. The 3.5R and 4R variants have been found to be more highly active than 3R or 5R, in a study which did not examine the 2R variant. An association between the 2R allele of the Variable Number Tandem Repeat region of the gene and an increase in the likelihood of committing serious crime or violence has been found.

"MAO-A levels in the brain as measured using positron emission tomography are elevated by an average of 34% in patients with major depressive disorder. Genetic association studies examining the relationship between high-activity MAO-A variants and depression have produced mixed results, with some studies linking the high-activity variants to major depression in females, depressed suicide in males, major depression and sleep disturbance in males and major depressive disorder in both males and females.
...
"The frequency distribution of variants of the MAO-A gene differs between ethnic groups. 59% of Black men, 54% of Chinese men, 56% of Maori men, and 34% of Caucasian men carry the 3R allele. 5.5% of Black men, 0.1% of Caucasian men, and 0.00067% of Asian men carry the 2R allele.

"A connection between a version of the monoamine oxidase A gene (3R) and several types of antisocial behaviour has been found. MAO-A had no statistically significant main effect on antisocial behaviour. Maltreated children with genes causing high levels of MAO-A were less likely to develop antisocial behaviour. Low MAO-A activity in combination with abuse experienced during childhood results in an increased risk of aggressive behaviour as an adult. High testosterone, maternal tobacco smoking during pregnancy, poor material living standards, dropping out of school, and low IQ can also trigger violent behaviour in men with the low-activity alleles (which are overwhelmingly the 3R allele).

"In individuals with the low activity MAO-A gene, when faced with social exclusion or ostracism showed higher levels of aggression than individuals with the high activity MAO-A gene. Low activity MAO-A could significantly predict aggressive behaviour in a high provocation situation, but was less associated with aggression in a low provocation situation. Individuals with the low activity variant of the MAO-A gene were just as likely as participants with the high activity variant to retaliate when the loss was small. However, they were more likely to retaliate and with greater force when the loss was large."

So to summarise and over-simplify: low levels of MAO-A lead to aggression; high levels lead to depression.

Egocentricity asserted itself at this point and my thoughts turned to my 23andMe genotype data. The 2R (two repeats), 3R, 3.5R, 4R, and 5R variants of the repeat sequence aren't looked at by 23andMe, as they only test for SNPs. However, the gene which codes for MAO-A also has alleles which differ in SNPs, specifically rs6323.

Only one nucleotide to report here for me as it's on the X-chromosome and I'm male. The variant which expresses the most MAO-A is the G-variant, which makes its carrier prone to depression.

I'm T: so a tiny bit more warrior than someone on antidepressants.

My 23andMe results

The results of my genetic screening at 23andMe have now come back - almost a million SNPs analysed.

[Update (August 2017): see also my Personal Genome Project report (PDF)].

The human genome SNP database currently has around 20 million known SNPs but most have unknown consequences.

So, here are the highlights: overall I guess I was pleased and relieved! The impact on family? Well, I share half of my alleles with my siblings, my parents and my children (and I'm uncorrelated with my wife). So extrapolate with care .. we're none of us clones.

I was a bit surprised to find that my paternal lineage appears to be from Ireland! We had traced my great-great-grandfather up to Oldham, Lancs where he was a Hatter (see here also). I think we had supposed the Oldham Seels were Anglo-Saxon, but the Y-chromosome is pointing instead to Ireland. On the maternal side, it seems my mother's maternal ancestors are solidly Atlantic coastal celts.

Click on images to make them larger.

Clare says just by appearance - Neanderthal is obvious!

The site itself has masses of detailed results and research reports which will keep me occupied for a while.