HYDERABAD: Long-term tracking of thousands of healthy Indian individuals has revealed that 25 per cent to 30 per cent became obese by adulthood, even though they showed no signs of the condition at the beginning. This finding is part of a global study that offers new genetic insights into obesity and introduces a polygenic risk score (PRS) capable of predicting the likelihood of developing obesity as early as age five.
The study involved over 600 scientists across 500 institutions, including researchers from Hyderabad-based CSIR-CCMB.
Led by senior geneticist Dr. Giriraj Ratan Chandak, CSIR-CCMB contributed to ensuring that the genetic data from Indian participants reflected South Asian diversity. Dr. Chandak told TNIE, “The study included four Indian cohorts, mainly from Mysore, Mumbai, and Pune, ranging from 2,200 to over 20,000 individuals, many of whom have been followed for nearly two decades.
The long-term data allowed researchers to assess how genetics and lifestyle together influence obesity progression over a lifetime.”
The study also found that individuals with a higher genetic risk are more prone to obesity but tend to respond better to lifestyle interventions, although they may regain weight more quickly when those interventions are discontinued.
Model proved more accurate for people of European ancestry
The PRS model proved more accurate for people of European ancestry compared to South Asians. The model, created using genetic data from over five million individuals of various backgrounds, was found to be twice as effective as previous models.
By integrating the influence of hundreds of thousands of genetic variants, it evaluates an individual’s risk of obesity, serving as a robust early-warning tool to inform preventive lifestyle adjustments.
“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,” said Dr. Roelof Smit, lead author and assistant professor at the University of Copenhagen’s NNF Centre for Basic Metabolic Research.
Dr. Chandak told TNIE, “This is one of the most extensive multi-ancestry studies ever conducted. It identifies genetic variants accounting for 18 to 20% of the genetic risk for obesity, almost triple what we previously knew. For India, it shows that precision prevention is possible but must go hand in hand with behaviour change.”
He added that the samples tracked over the years were mainly healthy individuals, and those who developed other diseases were excluded from the initial genetic assessments. The research also confirmed that obesity in Indians, which is often abdominal and visceral, follows a different genetic trajectory than in Europeans.
The senior geneticist said, “Many obesity-linked gene variants identified in European populations showed limited impact on Indians. In the future, we must create PRS models specific to Indian groups.”
Genetics is not destiny
Dr. Chandak explained that statistical methods like logistic regression were used to adjust for variables such as age and gender, and the effects of genetic variants were compared across populations. “While the methodology is consistent across ancestries, we found that the predictive power of genetic variants is significantly lower in Indians,” he added.
He also noted, “We tracked parameters like weight and nutrition every five years. While environmental influences cannot be normalised, genetic risk remains fixed, which allows for cleaner prediction models.”
This opens the door to targeted interventions in early life. “If I can predict at birth that a child may become obese by their teens, that child can be nurtured differently through diet and exercise before the disease manifests,” he said.
Future research
Future studies in India will aim to validate PRS models for other metabolic conditions such as diabetes and hypertension. These efforts will be led by the Sneha Consortium, a collaborative network of Indian scientists.
“Now that we have genotyped these individuals and followed them longitudinally, we can conduct blinded analyses to test whether these scores predict not just obesity, but future cardiometabolic disease,” Dr. Chandak said.
He added, “With the World Obesity Federation warning that more than half of the global population could be overweight or obese by 2035, this study arrives at a critical time. It affirms that while genetics offer predictive power, lifestyle and environmental interventions remain central to effective prevention, especially in regions like South Asia.”