Researchers used genetic data from more than 5 million people to develop a new score that helps to explain why some gain weight rapidly whereas others do not. The findings bring us closer to identifying – already in childhood – who is at greatest risk of developing obesity and to intervening early, says a researcher.
Body weight is complex.
Believing that people become overweight because they eat too much or exercise too little can be tempting, but lifestyle is only one part of developing obesity.
The other part is genes. Some people have a higher internal volume button for hunger, and others feel full more rapidly. In fact, genes can explain an estimated 40–60% of the difference in people’s body-mass index (BMI).
Researchers have developed a genetic score that accounts for 17% of the differences in BMI between people. That may sound modest, but in genetics it is a major leap – like finding the puzzle piece that suddenly makes the whole picture come into view. It provides such accurate predictions that it can identify with high certainty who is at risk of having obesity.
The potential is enormous.
“This means, for example, that children could be genetically screened to identify those at high risk of having obesity later in life. The score could become part of a health profile, alongside cholesterol or blood pressure, giving doctors a basis for earlier guidance or treatment. The children with a high risk of developing obesity who may benefit from lifestyle interventions at an early age can be identified,” explains the lead researcher behind the study, Ruth Loos, Professor, Vice Executive Director and Group Leader, Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, Denmark.
The research has been published in Nature Medicine.
The world’s largest data study provides accurate weight scores
Previously, researchers created a similar genetic score for the risk of developing obesity.
It was developed based on genetic data from 300,000 people and explained 7% of the variation between individuals.
The new genetic score was developed based on data from 5.1 million people and explains 17% of the variation between individuals.
Six hundred researchers from 500 institutions worldwide participated in collecting the data and developing the genetic score.
“The new score is a dramatic improvement on previous methods of predicting who will have obesity and who will not. It brings us closer to being able to use such a model in clinical practice,” says Ruth Loos.
Risk can be measured from birth
The algorithm behind the new score is especially good at predicting who will develop severe obesity, i.e. a BMI over 35.
Ruth Loos explains that the score is interesting because it provides an assessment that is independent of the person’s current weight.
For example, if you have overweight at the age of 30 years, imagining that you have an increased risk of having obesity at 40 years is not difficult. This is often the case.
The same can be said about people who are slightly overweight at the age of 20 years or even as teenagers or 10-year-olds.
Research has repeatedly shown that this correlation exists.
However, the correlation disappears for children younger than five years.
Children younger than five years who are overweight do not have a greater risk of having obesity at 40 years of age than children younger than five years who do not have overweight.
This is where the genetic score can be useful.
“We can calculate genetic risk from birth. It is like having a map of the terrain before you set out on a journey. This makes the test especially valuable because doctors can intervene early, before the person has a chance to develop obesity. It is important to understand that even if you are genetically predisposed to developing obesity, it is not necessarily your destiny. There are opportunities to intervene either through lifestyle changes or medication,” notes Ruth Loos.
New studies will test the score in practice
The study is part of a larger research project that aims to understand the genetic and biological components of developing obesity.
This means that researchers will be conducting further studies on the subject from different perspectives in the near future.
Among other things, the researchers are working on a study in which they have developed scores for how healthy or unhealthy a person’s excess weight is.
Some individuals may have obesity without this necessarily meaning that their blood sugar levels or blood pressure are elevated. They may simply carry a little more fat on their hips.
The score can determine this.
The researchers are also planning new studies to examine what the score can reveal about the effects of treatment with weight-loss medication or diets.
Previous studies have already suggested that people with a high risk score for severe obesity often lose more weight in lifestyle interventions but also tend to regain it more quickly afterwards. Other studies indicate that weight-loss medication is generally less effective for people with a high score than for those with a low score.
Genetics may indicate new treatments
A main objective of the overall research is to improve understanding of what the many genes that influence the risk of developing obesity actually do.
Many clearly play a role in the brain and in feelings of hunger and satiety, but researchers are investigating whether the genes affect other organs and tissues.
All this new knowledge is also of great interest to the pharmaceutical industry, which is searching for new targets for drugs to treat people with obesity – or ways to use existing drugs in new ways.
“It also enables us to determine whether approved drugs target some of the potential drug targets we identify. This would mean that new antiobesity drugs may not need to be developed and existing drugs could be used instead. We are currently analysing this,” says Ruth Loos.
