Cleared: dkHyderabad: In a major study, an international team of over 600 scientists from 500 institutions developed a genetic test — polygenic risk score (PRS) — which can predict adult obesity as early as age five. The study analysed data from over five million (50 lakh) individuals worldwide, with significant representation from India.Scientists from city-based Centre for Cellular and Molecular Biology (CCMB) played a key role in characterising the genomes of Indian individuals, including those monitored for diabetes over the long term. The south Asian data shaped PRS, making the findings especially relevant to the Indian context, where obesity-related disorders like diabetes and cardiovascular disease are on the rise. The tool, shown to be twice as effective as previous models, offers the potential for early lifestyle interventions in genetically high-risk children.CCMB researchers on Tuesday said that obesity increases the risk of non-communicable diseases such as diabetes, cardiovascular diseases, poor bone health, reproductive problems, and cancers. Scientists worldwide worked with the largest and most diverse genetic dataset ever assembled, which included genetic data from the GIANT consortium and the consumer DNA testing company 23andMe.In a statement, CCMB said: “The PRS discovery could help identify children and adolescents already at higher genetic risk of developing obesity, who could benefit from targeted preventative strategies such as lifestyle interventions at a younger age. Additionally, this score is twice as effective as the previous best test at predicting a person’s risk of developing obesity.”“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,” University of Copenhagen’s NNF Center for Basic Metabolic Research (CBMR) assistant professor Roelof Smit, who is the lead author of the research published in the journal ‘Nature Medicine’, said.Indian Representation in the StudyThe pattern of obesity in India differs notably from that in Europe, with Indians tending to have more central (abdominal) obesity. Earlier studies by Dr Giriraj Ratan Chandak at CCMB showed that the genetic basis of non-communicable diseases varies significantly between Indians and Europeans.In the latest study, researchers at CCMB, led by Dr Chandak, characterised the genomes of the Indian population, including individuals with diabetes as well as those with normal blood glucose levels. These individuals were followed for nearly 20 years, providing a unique opportunity to investigate the genetic basis of obesity in Indians. Several obesity-associated genetic changes were identified and used to develop PRS for Indians, effectively creating a “virtual individual” to model obesity risk.The Indian data served as a representative subset for the South Asian population in the global study, making the findings more applicable to India and neighbouring countries. The researchers also examined the link between a person’s genetic risk of obesity and the effectiveness of lifestyle-based weight-loss interventions, such as diet and exercise. They found that individuals with a higher genetic risk of obesity responded better to interventions — but also tended to regain weight more quickly once those interventions ended.The study further highlights the role of population ancestry in predicting obesity risk. Despite using a globally representative dataset, PRS performed more accurately in individuals of European ancestry than in those of other ancestries, including South Asians. Many gene variants associated with obesity in Europeans do not have the same effect in Indians, reflecting the unique pattern of obesity observed in the Indian population.“The observations made in this study are consistent with our earlier findings,” Dr Chandak noted.
