The idea that obesity is caused by a single "obesity gene" inherited from parents is an oversimplification, according to research by Inserm, a French public health institute. In reality, obesity is influenced by more than a thousand regions in the genome, along with rare cases where a single genetic mutation can lead to severe obesity. Studies show that people are two to eight times more likely to be obese if their family members are also obese. Research on twins suggests that between 40 and 70 percent of the differences in body weight between individuals can be explained by genetic factors. However, this does not mean a person’s weight is fixed from birth, but rather that genetics can make individuals more susceptible to environmental factors like diet and lack of physical activity. For most people with obesity, it is not a single defective gene that causes the condition, but rather the combined effect of many small genetic variations. Scientists from Inserm and CNRS have identified nearly 1,000 regions in the genome that are associated with increased weight gain. While each variation alone has only a minor effect, together they contribute to weight differences between individuals. However, these genetic factors explain only a small portion of the variation in weight, and their main role is to make some people more sensitive to environmental influences like food choices and lifestyle habits. There are also rarer forms of obesity known as monogenic obesity, where a mutation in a single gene is enough to cause severe and early-onset obesity. These cases are often linked to genes involved in the "leptin/melanocortin" pathway, which controls feelings of hunger and fullness. The MC4R gene is the most commonly affected, with over 100 different mutations identified in people with obesity. When this pathway is disrupted, it can lead to constant feelings of hunger, causing significant weight gain from a very young age. This distinction between common and rare genetic causes of obesity has important implications for treatment. Since 2021, specific treatments have been available in Europe for people with these rare genetic mutations. Medications that target the MC4R receptor can restore the satiety signal in these patients, leading to meaningful improvements in weight management. Specialized centers, such as the Pradort rare diseases center in France, use genetic testing to identify these rare forms of obesity and guide patients toward targeted therapies. However, this approach is not suitable for the more common polygenic form of obesity, where personalized care from healthcare professionals is recommended. Genetics does not determine a fixed destiny. Whether obesity is caused by many small genetic variations or a single mutation, genetics influences a person's susceptibility to weight gain, not a predetermined outcome. Research into epigenetics shows how the environment can influence gene activity without changing the DNA itself. This understanding challenges the idea that obesity is simply a matter of personal willpower. Instead, obesity is recognized as a chronic, multifactorial disease that requires a medical approach to weight management rather than judgment of the individuals affected.