Are Your Genes The Real Reason Why You Struggle With Weight Loss? Study Explains

Obesity in India and in the rest of the world often gets framed as a product of diet, activity and lifestyle. Those who gain weight fast and find it difficult to shed the kilos despite lifestyle changes and increase in exercise levels, however, will tell you that that's not always the case. So, what if our genes were silently shaping our propensity to gain weight too? A landmark international study published in Nature Communications reports that this might be the reason why some people struggle with weight loss so much. The study, in fact, discusses the discovery of five previously unreported genes linked to body mass index (BMI) and metabolic disease risk across ancestries.

For Indians, who now rank among the world's fastest-growing populations for obesity and diabetes, the findings provoke a significant shift. The research, involving over 800,000 individuals from six continental ancestries including South Asians, demonstrates that both rare, high-impact protein-truncating variants (PTVs) and the cumulative effect of many small genetic variants (polygenic burden) jointly influence who becomes obese and who remains lean despite similar lifestyles.

In fact, the study suggests that risk is layered. For India's doctors and public-health advocates, this means a fresh understanding of "why obesity" matters, not just based on what we eat or do, but also what we carry in our genome.

Obesity Can Be Caused By Genetic Factors: What Was Found And Why It Matters

Researchers analysed data from 839,110 adults drawn from the UK Biobank and All of Us Research Program cohorts, spanning six continental ancestries. They ran rare-variant association tests, identifying genes whose truncation or damaging mutation is strongly associated with higher BMI. Their key findings:

• Thirteen genes exceeded exome-wide significance for association with BMI. These included well-known loci such as MC4R and PCSK1, and five new ones: RIF1, YLPM1, GIGYF1, SLC5A3 and GRM7.
• Some of these variants showed effect sizes comparable to canonical obesity genes. For example, YLPM1 and RIF1 had impacts similar to MC4R.
• Clinically, people carrying damaging variants in genes like GIGYF1 and BSN faced higher odds of type 2 diabetes, hypertension or heart failure, mediated directly by the gene or indirectly via elevated BMI.
• Importantly, there was strong interplay between these rare variants and polygenic risk scores (PRS). When a carrier of a high-impact rare variant also had a high PRS for BMI, their obesity likelihood soared.
• The study emphasised ancestry-equity. Most genetic research to date focused on European populations. Here, only when diverse ancestries were included did they find signals generalisable across groups, reinforcing that genetic findings must reflect global diversity.

This resonates with prior work showing obesity's heritability at roughly 40-70% and implicating brain and appetite regulation pathways.

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Why This Matters In The Indian Context

India carries a unique burden of obesity, diabetes and cardiovascular disease, yet much of the prevention strategy treats weight gain as strictly lifestyle-driven. With the new genetics findings, several things shift:

• Explaining diversity: Two individuals in the same family, same diet and activity, may gain weight very differently. The new study shows that rare gene variants and polygenic burden may explain this.
• Early warning: Genetic screening (once affordable) could identify those at elevated risk of obesity and metabolic disease early, enabling preventive intervention years ahead.
• Personalised prevention: Instead of one-size-fits-all advice, high-risk carriers might benefit from more aggressive monitoring (for diabetes, hypertension) or tailored nutrition/exercise plans.
• Ancestry matters: Because South Asian populations are under-represented in genetic studies, the inclusion of multiple ancestries in this work means findings are more relevant for Indians, highlighting that global research must reflect global diversity if India is to benefit.

What You Can Do Now: Lifestyle Meets Genetics

While genetics set the template, they don't write the whole script. Carriers of high-risk variants still benefit from lifestyle changes. And indeed, combining lifestyle modification with knowledge of genetic risk may amplify results. Here are some steps you can take:

• Adopt a calorie-controlled, nutrient-rich diet because while genes may predispose, excess calories magnify risk.
• Prioritise regular physical activity. Vigorous aerobic and resistance training can offset genetic susceptibility.
• Monitor weight, waist circumference and metabolic markers early, especially if there's family history of obesity or diabetes.
• Consider asking your physician about genetic testing if you have unexplained difficulty maintaining healthy weight despite efforts, and ensure the testing is ancestry-appropriate rather than European-biased.

The latest study unravels a deeper layer of the obesity puzzle, revealing how rare gene variants and common genetic burdens combine to influence our weight and disease risk. For India, this is a wake-up call: While diet and activity remain foundational, our genome may hold answers to why some people struggle more than others to maintain healthy weight. The era of personalised prevention, powered by genetics, is upon us, and it's time we prepare.

Disclaimer: This content including advice provides generic information only. It is in no way a substitute for a qualified medical opinion. Always consult a specialist or your own doctor for more information. NDTV does not claim responsibility for this information.