‘Choose life, not fat’: Scientists develop PRS that can predict obesity well in advance

Hyderabad: Obesity, a growing global concern, affects people across age groups. It is a known risk factor for several non-communicable diseases such as diabetes, heart disease, certain cancers, and reproductive complications.

Now, an international research initiative has made significant progress in understanding the genetic basis of obesity, particularly its relevance to Indian and South Asian populations.

Global Study, Local Relevance

In one of the largest genetic studies of its kind, more than 600 researchers from over 500 institutions collaborated to examine the genetic underpinnings of obesity. By using data from the GIANT consortium and DNA testing firm 23andMe, the team analysed genetic information from over five million individuals worldwide.

One of the key outcomes was the development of a polygenic risk score (PRS) that can predict the likelihood of developing obesity well in advance, specifically during early childhood.

“What makes the score so powerful is its ability to predict, around the age of five, whether a child is likely to develop obesity in adulthood, well before other risk factors start to shape their weight later in childhood. Intervening at this point can have a huge impact,” said Assistant Professor Roelof Smit, from the NNF Center for Basic Metabolic Research (CBMR) at the University of Copenhagen and lead author of the research, which was published in Nature Medicine.

This PRS is reported to be twice as effective as the best existing predictive models for obesity risk.

Indian Cohorts at the Heart of the Study

In India, where lifestyle-related diseases are on the rise, obesity has become a pressing issue, particularly due to the distinct pattern of fat distribution, often central or abdominal, which differs from patterns seen in Western countries.

Recognising this difference, researchers at the CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, under the leadership of Dr. Giriraj Ratan Chandak, contributed crucial data from long-term studies on Indian populations. Their cohort included both individuals with diabetes and those with normal blood glucose levels, tracked over nearly two decades.

These Indian samples played a pivotal role in ensuring South Asian representation in the broader study. Researchers were able to identify genetic variations specifically associated with obesity in Indians and apply these findings to refine the PRS for the region.

A “Virtual Individual” to Model Risk

By using genetic data from the Indian cohort, the researchers created a “virtual individual” to model obesity risk in the South Asian context. This allowed them to simulate the impact of specific genetic variants and, in turn, predict risk more accurately for this population subset.

“The observations made from this study are similar to the earlier results on height, where genetic variants identified in Europeans predicted lower risk in Indians, and environment-related modifications of genes play a larger role,” said Dr. Chandak.

Genetics Is Not Destiny

While the study confirmed that genetics plays a significant role in determining obesity risk, it also offered encouraging insights into the impact of lifestyle interventions.

Individuals with a higher genetic risk showed better initial responses to lifestyle changes like diet and exercise, but also had a higher tendency to regain weight when the interventions ceased.

Interestingly, the study found that polygenic risk scores were more effective in predicting obesity among people of European descent than those from other ancestries, including South Asians. This underlines the importance of building diverse genetic datasets to improve the precision of predictive models.

Dr. Chandak added, “It looks like lifestyle, diet, and nutrition might be playing an equal or more important role in predicting obesity in Indians. So, for Indians, lifestyle solutions or specific nutrient supplementation in the background of genetic risk might yield better results.”

Looking Forward

The findings mark a step forward in personalised medicine and preventive healthcare. As more data from diverse ancestries become available, predictive models like the polygenic risk score can be better tailored to different populations, helping individuals understand their risk and adopt early, effective interventions.

For India and other South Asian nations grappling with rising obesity rates, the study offers both a scientific foundation and a practical direction: genetic risk may be a starting point, but lifestyle remains a powerful tool in prevention.