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expert reaction to study on genetics of weight in thin and obese people

Research published in PLOS Genetics suggests that thinness may be a heritable trait and may help inform the identification of anti-obesity targets.

Prof. Tim Spector, Professor of Genetic Epidemiology, King’s College London:

“This study highlights what we have known for the last 15 years from twin studies, namely that genetics are important in your propensity to be thin or obese. Generally thin people are more likely to have several thin relatives and obese people obese relatives. The genes found in this study add to the list found from larger studies and are helpful for understanding mechanisms but don’t help in individual prediction of obesity. About a third of people in most countries manage to remain thin despite exposure to poor food environments. Some of this is down to genes, but other factors like individual differences in lifestyle or gut microbes are likely to also be responsible.”

Prof Tom Sanders, Emeritus Professor of Nutrition and Dietetics, King’s College London, said:

“This is an important and well-conducted study confirming that the precocious severe obesity is often genetically determined and showing convincingly that those who very thin are genetically different from the general population. However, most obesity is acquired in adult life and is linked to the obesogenic environment we live in (a sedentary lifestyle and abundance access to calorie dense foods). Furthermore, genetic differences are unable to explain the large rise in the prevalence of obesity in children under 6 years old which may have its origin in pregnancy and early infancy when appetite is programmed in the offspring.”

Prof. Keith Frayn, Emeritus Professor of Human Metabolism, University of Oxford, said:

“Thinness and fatness are two ends of a spectrum. It is well established that excessive fatness (obesity) has a strong inherited component, so it is not too much of a surprise to find that the same is true for thinness.  An interesting finding from this study, though, is that not all the genes involved are the same.  These results do not tell us anything about why some people remain thin. In the press release Professor Farooqi says that “Some people are just not that interested in food whereas others can eat what they like, but never put on weight”, but the results do not bear out the idea that some people can eat whatever they like and never put on weight.  Nor is there any evidence for that point of view from physiological studies: almost all the evidence from genetic and physiological studies points to the fact that body weight is largely a reflection of how much we eat.  If there are people who can eat what they like and not put on weight, they either don’t want to eat much, or they are the regular exercisers.  People who exercise regularly were excluded by the authors from the thin cohort, so this is almost certainly a study of the genetics of low versus high energy intake.”

Prof. Timothy Frayling, Professor of Human Genetics, University of Exeter Medical School, said:

“This study is important because it shows very convincingly that genes influence body mass index at both ends of the scale – the thin end as much as the fat end. The authors have performed a very neat study because they were able to study a large number of people who were thin for no obvious medical problem – such as psychiatric diseases or losing weight because of cancer. The really interesting new thing is that being naturally thin seems to be largely the flip side of the genetic coin to being naturally overweight – the same genes seem to be involved, just in different forms.”

Prof. Waljit Dhillo, Professor in Endocrinology and Metabolism, Imperial College London and member of the Society for Endocrinology, said:

“The study has been conducted very well with good controls. The implications for the real world are that we have known that many genes are important that predispose obesity. What this study shows for the first time is individuals who are lean have a lower frequency of these genes that cause obesity, which makes sense biologically. It further highlights the importance that one’s genetics makes an important contribution to whether someone develops obesity or not.”

‘Genetic architecture of human thinness compared to severe obesity’ by Riveros-McKay et al. was published in PLOS Genetics at 19:00 UK time on Thursday 24th January 2019.

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