Obesity in India and around the world is ofen attributed to diet, activity, and lifestyle. However, those who rapidly gain weight and struggle to lose it despite lifestyle changes and increased exercise know this isn’t always the case.Could our genes be silently shaping our propensity to gain weight? A landmark international study published in Nature Communications suggests this might be true, revealing five previously unreported genes linked to body mass index (BMI) and metabolic disease risk across ancestries.
For Indians, who are now among the world’s fastest-growing populations for obesity and diabetes, these findings represent a important 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 analyzed 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 meaning 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 emphasized ancestry-equity. Most genetic research to date focused on European populations. here, only when diverse ancestries were included did they find signals generalizable 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 a