Obesity is 60% heritable. And this means …

Peter MolemanArticles, Genes and heredityLeave a Comment

Translated by Rumia Bose

I enjoy a good meal, as does my wife. I can eat what I like without much weight gain. And if I do gain more than I would like, I just eat a little less for a while. This is fairly easy for me. My wife on the other hand, while not being overweight, has to be more careful about her weight. I do not regard my being slender as a personal achievement. I think it is just my constitution. Is that heritability?

Heritability as a percentage?

You often see heritability being expressed as a percentage. Autism is 90% heritable, height 80%, BMI1 60%, musical aptitude 50%, depression 40%, breast cancer 30%. If height is 80% heritable, and you are 6 feet tall, does that mean that about 4’10” is determined by your DNA and 1’2” by something else? Obviously this is absurd. But then what do these percentages mean?

Twins and heritability

How are the percentages calculated? Various  methods are used, of which twin studies are the most common. Identical (monozygotic) twins are genetically identical, whereas fraternal (dizygotic) twins share only part of their genetic material. By comparing large numbers of identical and fraternal twins you have a measure of the genetic influence on a trait. This generally does not account for the total difference between identical and fraternal twins. The unexplained part is then attributed to environmental factors. This term refers to everything which they were subjected to and have learnt, such as upbringing, diet, and other experiences. But you still can not know from the experiment what these environmental factors are. In fact you do not even know if they really are environmental factors, because this is a blanket term for all non-genetic factors.

Heritability of overweight is 90%

Let us get back to the subject of obesity. This is often quantified in terms of BMI, or body mass index. This issue has been studied exhaustively, as obesity is a problem of modern society. Earlier I have stated that BMI is 60% heritable, but that is an average from numerous studies. The percentages range from 30 to 90%. In other words, from one third to almost entirely heritable. How can we account for this variation?
Consider carrying out a twin experiment. For this we select hundreds of pairs of twins, identical and fraternal, children2 of affluent parents and with similar diets. Some of these children are extremely overweight, some only slightly, others not at all. The most important environmental factors for obesity are socioeconomic status and dietary habits. These are approximately the same for all these twins. They have therefore no influence on the differences in weight of these children. Any difference in this situation can almost entirely be accounted for by heritability, let us say for 90%. Now we do a second experiment with pairs of twin children from a disadvantaged neighbourhood. The parents belong to the poorer sections of the population and they consume a considerable amount of fast food. Therefore, important factors related to obesity are present. The heritability of obesity here is… also about 90%, because here too the environmental factors are approximately the same for all these children.

Heritability of overweight is 30%

Let us now combine the two experiments. Or, a more elegant option, we conduct the experiment in exactly the same way in both neighbourhoods. This time the heritability of obesity turns out to be 30-40%! That is because relevant environmental factors – socioeconomic status and dietary habits – now show a large degree of variation in our research population. Genetic and environmental factors always add up to 100%. The amount of variation in each category determines their part in the percentage. If the variation in the genetic factor is very large, but the variation in environmental factors even larger, than the percentage of heritability is less than 50%. And if the relevant environmental factors can be kept constant, than the percentage heritability is 100%, even if the absolute role of heritability is actually very small.

Heritability in groups

The heritability percentage therefore depends on the group being studied. Most of the research on obesity has been done in the US and Europe, largely in white populations3. Those results cannot just be considered to apply to other groups. Research in Chinese populations, for example, show different percentages of heritability. What’s more, some of the heritability in Chinese populations is related to other genes, or other segments of DNA. Therefore heritability is related to DNA, but the relevant sections of DNA are not quite the same in different population groups.

What is inherited for obesity?

A heritability percentage for obesity below 30% has to my knowledge never been found in the research on this subject. This means that heritability always plays a substantial role. But this sort of research says nothing about what this role is. Other research has identified genes or sections of DNA which differ in obese and non-obese subjects. But despite much interest in this matter, the mechanism of genetic influence has yet to be found. One example is leptin, a hormone which has an influence on the feeling of satiety. Obese people are less sensitive to this hormone. It is thought that this is genetic. But after years of research it is yet unclear what part DNA plays in this, and the degree to which the hyposensitivity is genetic.

Can heritability and environmental factors be differentiated?

Does it make any sense to consider heritable and environmental factors as independent of each other? Your eating habits are also for a part inherited. Socioeconomiic status is partly related to capabilities which influence your chance of getting a well-paying job. These capabilities are also partially inherited. And on the other hand, the activity of your genes are for a part influenced by environmental factors4. Every human trait is heritable as well as acquired: see “Nature and nurture: congenital and acquired“. Genetic factors involved in obesity are therefore affected by environmental factors, and environmental factors are partly under genetic control.

What is the use of heritability percentages?

We can conclude that a heritability percentage is based on the mistaken premise that heritable and environmental factors are independent variables. What is then the point of all this research into heritability? It turns out that these findings can be of use to policymakers in government and healthcare. If you know the relevant factors for obesity in a particular population, then you can try to address this with specific measures for this group. Poverty is possibly the most important factor in disadvantaged families. Providing education about healthy diets and exercise is perhaps not the most relevant intervention. And the most important factor in obesity in people with a good income and healthy lifestyle may well be genetic predisposition. There is no way to correct this predisposing factor.

Conclusion

I have chosen obesity/ BMI as an example, but the above also holds for all complex human traits, that is for most of our traits. And also for many illnesses for that matter: autism, depression, breast cancer and many more. If you wish to know what role your DNA plays in determining a particular trait or in the risk of incurring a specific illness, then a heritability percentage is of no use. Neither will it tell you anything about your risk as a member of a population group, unless the experiment has actually been conducted in exactly the same group. Therefore, telling someone that their trait or illness has a specific heritability percentage is wrong.

References

Ludwig DS, Aronne LJ, Astrup A, de Cabo R, Cantley LC, Friedman MI, et al. (2021): The carbohydrate-insulin model: a physiological perspective on the obesity pandemic. The American Journal of Clinical Nutrition DOI: 10.1093/ajcn/nqab270

Harden KP (2021): “Reports of My Death Were Greatly Exaggerated”: Behavior Genetics in the Postgenomic Era. Annual Review of Psychology 72:null. DOI 10.1146/annurev-psych-052220-103822

Sun C, Kovacs P, Guiu-Jurado E (2020): Genetics of Obesity in East Asians. Front Genet 11. DOI 10.3389/fgene.2020.575049

Izquierdo AG, Crujeiras AB, Casanueva FF, Carreira MC (2019): Leptin, Obesity, and Leptin Resistance: Where Are We 25 Years Later? Nutrients 11. DOI: 10.3390/nu11112704

Blomquist GE (2019): Unpacking the heritability of body mass index and other ratios. Am J Hum Biol 31:e23289.

Schrempft S, van Jaarsveld CHM, Fisher A, Herle M, Smith AD, Fildes A, et al. (2018): Variation in the Heritability of Child Body Mass Index by Obesogenic Home Environment. JAMA Pediatr 172:1153–1160.

Loos RJ (2018): The genetics of adiposity. Curr Opin Genet Dev 50:86–95.

Moore DS, Shenk D (2016): The heritability fallacy. WIREs Cogn Sci doi: 10.1002/wcs.1400.

Silventoinen K, Jelenkovic A, Sund R, Hur Y-M, Yokoyama Y, Honda C, et al. (2016): Genetic and environmental effects on body mass index from infancy to the onset of adulthood. Am J Clin Nutr 104:371–379.

Feng R (2016): How much do we know about the heritability of BMI? Am J Clin Nutr 104:243–244.

Footnotes
  1. BMI= Body Mass Index: weight in kg divided by height in metres squared
  2. The same applies if adults are investigated
  3. A more detailed description of the ethnic groups involved would be informative
  4. An example: the lactase gene is activated by lactose from milk and the gene is inactivated after weaning

Leave a Reply

Your email address will not be published. Required fields are marked *