As mentioned in one of our previous blog posts, talking about genes in the context of obesity is often not well received.  Those discounting their role in the development of obesity often argue that, because genes have not substantially changed over the past 200 000 years, whereas obesity levels have only been soaring over the past 20 odd years (where it became possible to mass-produce cheap, tasty food in combination with a decreased need for physical activity), obesity must be due to changes in the environment, and not genetics.

However, using this argument against the heritability of obesity is somewhat flawed, because it ignores that a condition can be dormant over a period of time until the right circumstances bring it to life.  The gardeners among you will know that many plants will adjust their growth according to their surroundings – a plant in a small pot will remain small, whereas a larger pot will allow it to grow.   This, however, does not mean that the plant loses its ability to grow larger in a smaller pot; it merely remains small because its surroundings restrict its growth.  Similarly, genes predisposing to obesity may be present in an environment where little food is available, but without the right ‘medium’ (i.e. food), this is of little consequence.  In the current environment, however, where eating opportunities are plentiful, obesity genes can express their full force.

If obesity was resulting purely from environmental change, all individuals exposed to this change would become overweight.  Yet, this is not the case. In fact, the proportion of lean people has not substantially changed, but large people are becoming even larger.  This suggests that people respond to the food environment differently.  However, undoubtedly, to gain more weight than is healthy, food must not only be available in sufficient quantities, but one must ingest more of it than necessary.  Therefore, researchers started to look at differences in eating behaviours, such as how much we are drawn to food and how quickly we feel full, to see what is going on.

Twins can help to untangle the influence of genes and environment on obesity, because identical twins are 100% genetically identical, whereas non-identical twins only share approximately half of their genes (like normal siblings); both, however, grow up in a very similar environment.  This means that researchers can compare identical twins’ resemblance for weight with that of non-identical twins; if genetically identical twins are more similar in a trait than non-identical twins, it is evidence for genes being responsible for the trait.

Using twins, researchers from our department wanted to see whether genes that influence weight also influence appetite.  If the same genes that influence weight also influence appetite, it suggests that genes influence weight through their effects on appetite – i.e. individuals who inherit more avid appetites might be more susceptible to overeating in the modern food environment, and consequently  more likely to gain excessive weight.  They looked at this in infants, because infants are exclusively milk-fed, which ruled out that other factors such as preference for certain foods would influence the results.   The researchers used questionnaires to ask parents about how fast their twins fed, how easily they got full and how big their appetite was, and related the answers to the babies’ weight.   Because they used a sample of identical and non-identical twins the researchers were able to explore the extent to which appetite is heritable, and the extent to which appetite and weight are caused by the same genes.

They found that identical twins were not only very similar in weight, but shared many more similarities in appetite than non-identical twins, suggesting a strong genetic basis to both appetite and weight.  In addition, the results  showed that a substantial proportion of the genes that are responsible for weight are also responsible for appetite, in line with the idea that genes influence weight through appetite.  These findings lend evidence to the idea that some of us are more likely to overeat in the current environment because of a larger appetite, which is ultimately driven by genes.

These discoveries will hopefully contribute to reducing the stigma that surrounds unhealthy weight gain; because it clearly shows that those struggling with weight are in a sense ‘battling against their biology’.  This of course, does not mean that there is nothing that can be done about it; however, acknowledging these differences as real and designing strategies to ‘outsmart’ one’s genes is crucial if the battle is to be fought successfully.

Article reference: http://www.ajcn.org/content/95/3/633.long

There it sits, on the counter, the vial which holds the key to knowledge, everything from ancestral lineage over earwax texture to my memory capacity. My strengths and weaknesses, the key to who I am…at least in genetic terms.

Proponents for direct to consumer genetic testing claim that a bit of spit contains everything I could possibly want to know about myself. The skeptics call it a genetic horoscope, as most results are no more accurate than traits attributed to star signs.

In recent years, companies emerged which offer genetic testing over the internet and promise to tell you more about your health and ancestry than you ever imagined.  With a couple of mouse clicks you can order one of their test kits, spit into a collection tube, seal it, send it back and within a few weeks you receive an email containing the link to a website which reveals your risk for a myriad of traits and diseases, half of which I would have trouble spelling, let alone pronounce.

Of course, doing a PhD in the subject calls for some self-experimentation, so my supervisor thought it would be a good idea for me to experience what this feels like … and this is how I ended up with a plastic tube full of spit.

It took me 3 days to send it off (apologies to the poor person in the lab who has to open that stinky tube). Why did it take me so long, I wonder? I consider myself as a curious individual interested in the latest scientific discovery, open to adopt new technologies…so why the hesitation?

I guess, because it felt like it could bring something to light which I might have happily left lurking in the dark. The 23andMe test I took reveals my risk for over 100 health conditions, some of which are quite severe, such as my risk for Huntington’s disease, Alzheimer’s or breast cancer. In addition, it shows my carrier status for various genetic diseases; my reaction to certain medications and finally personal traits such as memory capacity or the likelihood of ending up as an alcoholic. That, dear readers, is a lot of information. All at once, on one page.

Do I even want to know all of this? Even if I know that no cure exists for most of the diseases listed? The answer is: sort of. But, at this stage, only very few gene results can give meaningful risk estimations; most give only a minute indication of any change in risk – be it for better or for worse. The problem is also that conditions with exclusively genetic cause, such as Huntington’s Chorea, are listed with conditions where the picture is more complicated (for example in obesity).  This makes it very hard to know how much meaning to attach to a single risk result. I know I would be better off taking a long and hard look at my family history, if I wanted to get an idea of which diseases may be befalling me one day.

Nonetheless, I was incredibly curious to find out, and although my rational brain immediately told me that the results didn’t mean anything in the grander scope of things, they were all but unimportant. I felt something, and I definitely focused much more on the conditions where I was at a ‘higher risk’ than on those where I was classified as ‘average’ or ‘reduced risk’, regardless of what the actual risk estimation was.

The companies which provide direct to consumer genetic testing take quite a risk: They are providing medical results with minimal advice for conditions that many people may never have heard of, with risk estimations that don’t mean much objectively, but nonetheless seem to have an emotional impact – there is a lot of room for misunderstanding here.

For example, if I found out that my genetic risk of lung cancer is 6.8 % instead of the average of 6.2 %, then objectively that tells me that there is a whole host of factors other than my genes that play a role – however, because it is my personal  risk, it has some emotional meaning and in response

1. I could do the wise thing and stop smoking- advocates of these tests hope that we are using the information that we received to change our behaviour and prevent eventual illness

2. I could panic and ring my doctor for immediate 3 monthly check-ups – opponents of direct-to-consumer genetic testing fear that it might lead to unnecessary medical procedures

3. I could think that I will get lung cancer anyway and smoke even more, because of it – another concern of those cautioning against direct-to-consumer genetic testing

What will I do? What will other people do? I wouldn’t have been able to say before I took the test, because there is very little research on the subject to date. Now I know I will definitely not worry. But someone else might. It is an utterly individual experience, and there is certainly a good portion of narcissism attached.

Will I change anything? At the moment I am doing quite a lot of the ‘right’ things anyway, like being fairly active and eating sensibly (let’s keep quiet about the drinking) – but I’d like to think that it will have an impact when I am older. I think that it can be a positive influence on one’s health, because it raises awareness of potential illness and may be a motivation to look after oneself. Would I recommend it? Yes, but only if one is aware of the shortcomings of these tests, and if there is good information available about what the result means.

Despite all its criticisms, receiving those genetic results was a very unique experience, and I found out some things I am quite glad about. My eyes really are blue.  One thing, however, I didn’t look at: my genetic risk for Alzheimer’s disease. I think it would have been too disturbing to find out that I am more likely to get a severe illness for which there currently is no cure. But that was my individual choice. And that is what personalized genetic testing is all about.

Would you get tested? Why? Why not? Let me know below or send an email to Susanne.meisel.09@ucl.ac.uk

Mentioning genetics in the context of weight is like treading into a minefield; those who are brave enough to approach the topic need to don their hard hats and be prepared to take hits by followers in the ‘eat-less-and-move-more’ camp. Accusations of laziness, lack of willpower, making excuses and just looking for an easy way out are common responses to the genetic argument of obesity.

However, to ignore genetics when talking about obesity is somewhat confusing when considering how keen people are to attribute skinniness to ‘good genes’, ‘fast metabolism’, and ‘being naturally active’. Nobody seems to notice that skinniness and fatness are two sides of the same coin.

As so often in life, the truth lies somewhere in between. While behaviour is certainly not to be ignored when searching for the root cause of the obesity epidemic, neither should the heritability of body weight. Two recent studies from our research group add evidence to the idea that the predisposition to thinness, as well as to overweight, is transmitted across generations. Researchers used data from the Health Survey for England, which included a large sample of families with children aged 2-15 years to see whether thin children were more likely to have thin parents. Of the thousands of families included in the first study, it was shown that thin children were almost twice as likely to have 2 thin parents.  Furthermore, as parents’ weight decreased, children likewise got progressively lighter.

But, what about the reverse side of the coin – parental weight of children who were overweight? Here, exactly the same pattern was found, but it was even more apparent. Children, who had 2 obese or severely obese parents, were approximately 12 times more likely to be overweight and again the likelihood of obesity gradually decreased with decreased parental body weight. In both studies, findings were unrelated to other factors such as age, sex, social status or ethnicity. Interestingly, the mothers’ weight seemed to be more predictive of a child’s than the father’s, but only among those children that were overweight. For thin children, mothers’ and fathers’ genes appeared to contribute equally to being thin.

Two things are important here. Firstly, weight is governed in part by genetic factors; but, and this is the second important conclusion to take away, there are environmental factors involved that influence a child’s weight – otherwise all children would have had parents that fully resembled their weight status. Influences seem to come especially from the mother’s side, which may be, because the foetus receives nutrients from the maternal diet in the womb and after birth when the infant is breast-fed. In addition, maternal environmental influences may be stronger because the mother is usually in charge of food preparation.

Unfortunately, dietary records of participants were not available, so it was not possible to investigate how diets between underweight and overweight children and their parents differed.

Genes do not always act in the same way; their activity is influenced by the environment. This flexibility allowed our species to adapt well to changing environmental conditions, which made it possible to survive and evolve.  Variation is the key. And this is why it is easier for some than for others to (not) have their cake and eat it, too.

References:

Whitaker KL, Jarvis MJ, Boniface D, Wardle J. Inter-generational transmission of thinness. Archives of Pediatrics and Adolescent Medicine. http://archpedi.ama-assn.org/cgi/content/full/165/10/900

Whitaker KL, Jarvis, MJ, Beeken RJ, Boniface D, Wardle J. Comparing maternal and paternal intergenerational transmission of obesity risk in a large population-based sample. American Journal of Clinical Nutrition. 91, 2010, 1560-1567. http://asn-cdn-remembers.s3.amazonaws.com/f8ee4cfad55bd34900cff3371b9a146d.pdf