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The genetics of obesity

Unfortunately genes do matter when it comes to obesity, but knowledge about these genes and how they work are key to improving treatment and prevention.

“Over the past two decades, genetic association studies have identified hundreds of genetic variations that affect body weight. Individuals who inherit many of these variations are more susceptible to gaining weight,” explains Ruth Loos, Professor at Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, to NLS.

The main drivers behind these recent discoveries are genome-wide association studies (GWAS) with increasing sample sizes and advances in sequencing technology (Loos and Yeo, Nature Review, 2021). However, it is the post-GWAS, cross-disciplinary collaborations, which combine new omics technologies and analytical approaches, that have started to facilitate the translation of genetic loci into meaningful biology and new avenues for treatment, the two authors explain.

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Genes interact with the environment

Ruth Loos is a pioneer in the understanding of the genetic component associated with the development of obesity. Last year Loos was awarded the Obesity Prize for Excellence, established by the European Association for the Study of Obesity and the Novo Nordisk Foundation. In 2007, she helped identify the first locus on the human genome that could be associated with an increased risk of developing obesity. This paved the way for identifying the second locus on the genome related to the risk of developing obesity, and since then she has been the leading force in the Genetic Investigation of Anthropometric Traits consortium, which has identified more than 1,500 loci in the human genome associated with BMI.

We know from twin and family studies that the genetic contribution to obesity is around 50%.”

“We know from twin and family studies that the genetic contribution to obesity is around 50%,” says Loos. “This means that 50% of all the variation in body weight seen among people in a population is due to genetic differences, whereas the other 50% of the variation in body weight is because people live in a different environment and have different lifestyles.”

However, a high genetic predisposition does not mean a person is destined to have obesity, continues Loos. “Studies have shown that a healthy lifestyle, including physical activity and a healthy diet, can attenuate one’s genetic predisposition to obesity by around 30%. Thus, genes interact with the environment in determining body weight.”

Loos and her colleagues have initiated one of the most in-depth mappings ever of the genetics and metabolism of 10,000 people, not only to determine why they have the BMI they do but also to learn more about their risk for developing diseases such as metabolic and cardiovascular diseases. The researchers will follow the participants for 25 years.

Childhood obesity

Estimates show that one in three children is overweight or obese in Europe (WHO, 2022). Ruth Loos and her colleagues have initiated a project where they will genetically map 16,000 children and their mothers with the aim of discovering whether the proteins expressed in their blood can be used to predict who will develop obesity later in life.

Studies have shown that 55% of children with obesity become adolescents with obesity and 80% of adolescents with obesity become adults with obesity, indicating that body weight and weight gain in early life are key determinants for future adult obesity.”

“Our primary focus for the project is identifying the genetic and proteomic determinants of early weight gain. Studies have shown that 55% of children with obesity become adolescents with obesity and 80% of adolescents with obesity become adults with obesity, indicating that body weight and weight gain in early life are key determinants for future adult obesity,” says Loos.

In contrast to other chronic diseases, such as type 2 diabetes, obesity is, or has become, an early-onset disease. Thus, being able to identify children at risk will be key in the prevention of childhood, and thus adulthood, obesity, emphasizes Loos.

“We aim to identify genetic variations and proteins that are associated with weight gain early on in life, which ultimately can help identify individuals who are at risk of future obesity, allowing timely prevention/intervention,” she concludes.

Featured photo of Ruth Loos: Ricky John Molloy

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