Obesity and Genetics

Obesity is defined as abnormal or excessive fat accumulation that may be harmful to health. One of the key questions surrounding this condition is whether obesity is genetic or hereditary. Among the various methods used to measure and classify obesity, the most commonly used is the Body Mass Index (BMI).
BMI is calculated by dividing body weight in kilograms by the square of height in meters (kg/m²), and the following obesity grades are defined:

• Grade 1: BMI between 30 and 35 kg/m²
• Grade 2 (Severe obesity): BMI between 35 and 40 kg/m²
• Grade 3 (Morbid obesity): BMI over 40 kg/m²

In adults, the World Health Organization (WHO) defines obesity as a BMI equal to or greater than 30. Progression toward obesity involves changes in adipose tissue characteristics and the development of low-grade chronic inflammation. This condition is marked by elevated levels of free fatty acids in the cardiovascular system, pro-inflammatory factors, and the activation and infiltration of immune cells at inflammation sites.

Obesity is also often accompanied by dyslipidemia, a metabolic disorder characterized by elevated levels of cholesterol and triglycerides in the blood—one of the major risk factors for developing ischemic heart disease.

Obesity in Numbers

According to WHO data, obesity has nearly tripled worldwide since 1975. Their latest estimates from 2016 indicate that over 650 million adults aged 18 and older were obese, accounting for 13% of the global population in that age group. Most of the world’s population now lives in countries where overweight and obesity cause more deaths than undernutrition—defined as having a BMI lower than what is considered healthy.

When it comes to childhood obesity, the WHO reported that in 2016, 41 million children under the age of five were overweight or obese. In the same year, more than 340 million children and adolescents (ages 5–19) were affected by overweight or obesity.

Health Risks Associated with Obesity

Obese individuals are at high risk of developing numerous conditions that can significantly affect their daily lives and increase their risk of death, including:

• Cardiovascular diseases such as coronary artery disease, heart failure, hypertension, stroke, atrial fibrillation, and sudden cardiac death
• Gastrointestinal disorders including GERD, functional dyspepsia, IBS, diverticulosis, IBD, pancreatitis, and GI cancers. Obesity may also negatively affect the response to treatment in these conditions
• Type 2 diabetes, especially when obesity develops in childhood or adolescence, increasing the risk in young adults
• Musculoskeletal disorders, which vary depending on the degree of obesity. The extra weight places chronic stress on bones and muscles, leading to conditions such as osteoarthritis, lower back pain, osteoporosis, and rheumatoid arthritis
• Psychological issues, particularly depression. A bidirectional relationship exists: obesity increases the risk of depression, while depression can predict the onset of obesity. There are also multiple biological pathways linking stress and obesity

Causes of Obesity

Obesity is a multifactorial disease that can result from energy imbalance, certain genetic or endocrine disorders, or the use of specific medications. Energy imbalance occurs when calorie intake exceeds energy expenditure, leading to fat storage and ultimately obesity.

When it comes to genetics, several syndromes of genetic origin are associated with obesity, such as Prader-Willi syndrome and Bardet-Biedl syndrome. There are also relevant endocrine disorders, including:

• Hypothyroidism, although its causal link to obesity remains controversial. While hypothyroidism is associated with weight gain, recent studies suggest that elevated TSH levels may be a secondary effect of obesity.

Additionally, obesity can result from the side effects of medications such as corticosteroids, antihypertensives, antidiabetics, or antidepressants.

Risk Factors

Obesity-related risk factors can be non-genetic or environmental, such as physical inactivity, age, poor diet, or sleep deprivation; or genetic, typically linked to mutations in metabolism-related genes.

There is growing evidence of gene-environment interactions in obesity, confirming a genetic connection. Research has shown that genetic factors contribute 40–70% to BMI variability.

Numerous dietary intervention studies demonstrate how individuals respond differently to low-calorie diets depending on genetic variants—especially those associated with obesity, type 2 diabetes, metabolism, and food preferences. These findings support the use of precision dietary interventions based on an individual’s genetic predispositions.

Prevention

Most cases of obesity and its complications are preventable. WHO recommends:

• Limiting fat and sugar intake
• Increasing the consumption of fruits, vegetables, legumes, whole grains, and nuts
• Engaging in regular physical activity

Preventive measures should be tailored to each individual, especially in cases where genetics plays a significant role in the development of obesity.