Each of us has wondered at least once why some people seem to eat whatever and whenever they want and still remain slim, while others, despite taking all measures like eating healthy, sticking to a routine, and exercising religiously, always struggle with weight-related issues.
The answer is not as simple as being a matter of luck. It runs much deeper — hidden in our genes — and is known as genetic predisposition.
Obesity is a medical condition clinically defined by a Body Mass Index (BMI) of greater than or equal to 30 kg/m², or greater than or equal to 25 kg/m² for Asian populations. It is characterised by excessive body fat accumulation that can negatively impact health and quality of life. This condition is not only a consequence of lifestyle choices but a multifactorial disorder.
Obesity is a major global health concern, with its prevalence increasing worldwide. At the current rate, it is projected that by the end of 2025, approximately one billion adults — nearly 20% of the global population — will be living with obesity.
On a simple level, one understands weight as a game of calories consumed and expended. If we consume more energy than we burn, we end up gaining weight. On the contrary, if we burn more calories than we consume, we lose weight. But it is not such an easy phenomenon. It is an interplay of many factors, including genetics and environmental influences such as diet and physical activity.
This is where genetic predisposition comes into the picture. It is defined as an increased likelihood of developing a particular disease based on a person’s genetic makeup. A genetic predisposition results from specific genetic variations that are often inherited from a parent.
Obesity is an epidemic affecting not only adults but also children. Around 50% of the time, obesity in childhood is carried into adulthood — a phenomenon known as tracking. Obesity itself is multifactorial and occurs due to complex interactions between genetics and the environment.
The Human Genome Project was carried out between 1990 and 2003 to map the human genome. Genome-Wide Association Studies (GWAS) have been ongoing since 2007 to help associate specific genetic variations with certain diseases. Around 250 genes are now known to be associated with obesity. The FTO gene (Fat Mass and Obesity-Associated gene) on chromosome 16 is considered the most important and carries the highest risk of the obesity phenotype (the set of observable physical characteristics of an organism).
Epigenome-Wide Association Studies (EWAS) began in 2013 to map the epigenome and understand the varied expression of genes in different tissues. GWAS and EWAS have together begun a new era in the study of genetics and obesity.
The concept of epigenetics was introduced to help understand the heritability of obesity better. It was first proposed by Waddington in the 1940s and elaborated by Holiday in 1990. The modern definition, given by Riggs et al. in 1996, describes epigenetics as “the study of mitotically heritable changes in gene expression that occur without changes in the DNA sequence.”
In simpler terms, epigenetics refers to how our behaviours and environment can cause changes that affect how our genes work. This further explains how the environment plays a significant role in influencing how our genes are expressed.
The expression of genetic influence on weight varies from person to person. Research suggests that, in some cases, genes can account for as little as 25% of weight predisposition, while in others, it may be as high as 70–80%.
Genetic causes of obesity can be either polygenic (multiple genetic factors) or monogenic (a single genetic factor). Based on this, genetic obesity can be classified into categories depending on how many and which genes are involved:
- Monogenic obesity: Excessive weight caused by a mutation in a single gene.
- Polygenic obesity: Variations in multiple genes contribute to the likelihood of obesity. This is the most common type of genetic obesity.
- Syndromic obesity: Genetic changes in specific diseases, such as Prader–Willi Syndrome, can directly lead to obesity.
Along with weight, genetics also influence several other factors:
- Taste buds and cravings: It’s not just about how our body uses food — our genes also influence what kind of food we prefer. For example, some people are more sensitive to bitter tastes, making them automatically averse to bitter vegetables and foods. Others may naturally love sweet or fatty foods. Even our genes can influence how our brain responds to foods high in sugar and fat, which can trigger self-reward mechanisms.
- Appetite and satiety: Hormones like leptin and ghrelin regulate appetite and fullness. Genetic variations can affect the production and function of these hormones, delaying the signal of fullness even after overeating — leading to overeating and weight gain.
- Metabolism: In earlier times, our ancestors depended on hunting and agriculture. In case of food scarcity, evolutionary adaptations helped them survive by conserving energy and storing fat — through genes known as “thrifty genes.” In today’s context, these genes have become a disadvantage, as food is abundant and available 24×7. These genes influence metabolic rate — some individuals have higher metabolism (burning calories faster), while others have slower metabolism, making them more prone to weight gain.
- Fat storage: Genes also determine fat storage patterns — whether the body stores fat around the abdomen (apple-shaped obesity) or hips and thighs (pear-shaped obesity).
An overview of the FTO gene:
The FTO (Fat Mass and Obesity-Associated) gene is the most important and widely studied gene linked to obesity. People with variations in this gene are more likely to have a higher BMI and increased risk of obesity. However, this does not mean that having this variation makes it inevitable for someone to be overweight. It simply indicates a higher risk due to genetic predisposition.
Indicators of genetic influence on weight:
Genes may be a probable contributor to obesity if:
- An individual has been overweight for most of their life.
- One or both parents (or blood relatives) have a history of being overweight or obese. The chance increases up to 80% if both parents are obese.
- There is difficulty losing weight despite following a healthy diet and regular physical activity.
Genes may be a lower contributor if:
- An individual’s weight is strongly influenced by food habits.
- Weight gain occurs occasionally but can be managed easily through lifestyle changes.
- Weight is regained after holidays, festivities, or brief lapses in diet and exercise routines.
Truth Beyond the Genes:
It is true that genetic predisposition puts individuals at higher risk of gaining weight, but it is not the only governing factor. The environment also plays a huge role. Today, we live in an “obesogenic environment” — one that promotes weight gain and discourages weight loss due to factors like the high availability of energy-dense, processed foods; limited access to healthy foods; sedentary lifestyles; and social and cultural norms surrounding calorie-dense festive foods.
This means that individuals with a genetic tendency to gain weight find it much easier to put on weight and much harder to lose it and stay healthy.
Other factors influencing weight include:
- Sleep: Proper and sound sleep is crucial for weight management. Any disturbance in sleep cycles can lead to hormonal imbalances and increased cravings for sweet or junk foods.
- Stress: Chronic stress can lead to weight gain by releasing the stress hormone cortisol.
It is evident that genetics plays a vital role in weight management, but certain lifestyle modifications can help overcome genetic predisposition and lead to a healthier life — primarily through healthy eating habits, regular physical activity, stress management, and adequate sleep.
Finally, we can say that the relationship between weight and genetic predisposition is complex and multifactorial. Although genetics play a significant role in weight patterns, they can be greatly influenced by environmental factors and lifestyle.
