Genetic Predisposition: How Much Do Our Genes Determine Our Health?

Our genes form the biological foundation upon which the human body develops and functions. They influence immediately visible characteristics, such as eye color, as well as much more complex functions, including metabolism, immune response, blood pressure regulation, and predisposition to certain diseases.

However, the presence of a genetic variant associated with an increased risk of a particular condition does not necessarily mean that the condition will develop. For most common chronic diseases, health is shaped by a complex interaction between genetic predisposition, the environment, and lifestyle.

Modern genetics, therefore, does not simply examine whether a specific “disease gene” is present. It also investigates how different genetic variants can influence risk, how they interact with one another, and how their effects may vary with factors such as diet, physical activity, smoking, sleep, environmental exposure, and age.

Understanding this relationship is essential for correctly interpreting the concept of genetic predisposition. Genes can significantly influence the likelihood of developing a disease, but in most cases they do not determine the final outcome on their own.

What Is Genetic Predisposition?

Genetic predisposition refers to an increased or decreased likelihood that an individual will develop a particular trait or condition due to specific variations in their DNA. Genetic variants are a normal part of human genetic diversity, and most do not cause disease.

Their effects, however, can vary considerably. In some cases, a pathogenic variant in a specific gene can have a strong effect and be associated with a monogenic disorder. In other cases, dozens, hundreds, or even thousands of genetic variants each make a smaller contribution to the overall predisposition to a complex trait or disease.

It is therefore important to distinguish between two different situations:

• In monogenic disorders, a pathogenic variant in a specific gene may be the primary cause of the disease. Even in these cases, age of onset and symptom severity may vary between individuals.
• In multifactorial diseases, such as type 2 diabetes mellitus, hypertension, and many cardiovascular diseases, the genetic component is one of several factors that determine overall risk.
   

A large proportion of the conditions addressed by modern preventive medicine belong to the second category. For this reason, genetic predisposition is more appropriately viewed as a factor that modifies the likelihood of developing a condition rather than as a definitive prediction of what will happen in the future.

Genes and Environment: Why Predisposition Does Not Mean Certainty

For many years, the discussion surrounding heredity and health was often framed as a choice between “genes” and “environment.” Today, we know that this distinction is overly simplistic. For most complex traits and chronic diseases, the final outcome results from the continuous interaction between genetic and environmental factors.

For example, an individual may carry genetic variants associated with a greater likelihood of weight gain, impaired glucose metabolism, or elevated lipid levels. This does not mean that these metabolic disturbances will necessarily develop. Their actual manifestation is also influenced by diet, physical activity, age, body weight, smoking, sleep, and many other factors.

Similarly, the absence of a known genetic predisposition does not guarantee protection. An individual with a relatively low genetic risk may still develop a multifactorial disease when significant environmental or metabolic risk factors are present.

This relationship is often described as a gene–environment interaction, meaning that an environmental factor may have a different effect depending on an individual’s genetic background. Therefore, not everyone responds the same way to the same diet, exposure, or living conditions.

Which factors can influence the expression of genetic predisposition?

The factors that interact with our genetic background are numerous, and their significance varies depending on the trait or disease being considered. Some of the most important include:
 

• Diet, total energy intake, the quality of dietary fats, and the intake of carbohydrates, protein, fiber, vitamins, and other dietary components can interact with metabolic pathways influenced by genetic factors.
• Physical activity influences glucose regulation, insulin sensitivity, body weight, muscle function, and cardiovascular health, in some cases reducing the impact of an increased genetic predisposition.
• Smoking and alcohol consumption are environmental exposures that can significantly modify the risk of certain conditions, both independently and in combination with an individual’s genetic background.
• Sleep and chronic stress are associated with hormonal and metabolic changes and can affect parameters such as appetite, glucose regulation, and the inflammatory response.
• Age and overall environmental exposures also influence how genetic risk manifests throughout life.
   

Therefore, genetic information has greater practical value when assessed alongside an individual’s actual biological and clinical profile. Two people with a similar genetic predisposition may have very different metabolic and clinical profiles, precisely because genetic background represents only one part of the overall equation.

How genes influence the risk of chronic diseases

Researchers have extensively studied genetic predisposition in many common chronic diseases. In most cases, no single gene determines whether an individual will develop a disease. Instead, multiple genetic variants influence different biological functions and, together with other risk factors, shape the overall likelihood of developing a disease.

Typical examples include:

• Cardiovascular diseases: genetic variants can influence lipid metabolism, blood pressure, the inflammatory response, and other mechanisms related to cardiovascular health. Actual risk, however, also depends on factors such as cholesterol levels, blood pressure, smoking, diabetes mellitus, diet, and physical activity.
• Type 2 diabetes mellitus: numerous genetic variants have been identified that are associated with pancreatic beta cell function, insulin secretion and action, and glucose metabolism. Obesity, physical inactivity, age, and dietary habits nevertheless continue to play a major role in the development of the disease.
• Obesity and body weight, genetics can influence appetite, satiety, energy expenditure, and the tendency to store fat. However, body weight is a highly complex trait and cannot be predicted based on individual genetic variants.
• Osteoporosis, bone mineral density, and fracture risk have a significant genetic component, but are also influenced by age, hormonal changes, diet, physical activity, body weight, certain diseases, and the use of specific medications.
   

Similar interactions are observed in many other conditions. This helps explain why even members of the same family, who share a substantial proportion of their genetic material, do not necessarily develop the same diseases, or may not develop them at the same age or with the same severity.

What Genetic Tests Can and Cannot Tell Us

Genetic tests can provide different types of information depending on the purpose for which they are performed. Therefore, not all genetic tests are equivalent, nor do they answer the same clinical questions.

A basic distinction can be made between tests that assess genetic predisposition to complex traits and diseases and those that investigate pathogenic genetic variants associated with specific inherited disorders.

Genetic predisposition tests

Genetic predisposition tests typically examine common genetic variants, such as single nucleotide polymorphisms (SNPs), which may be associated with small differences in the risk of developing a particular trait or multifactorial disease.

In some cases, information from many such variants can be combined into Polygenic Risk Scores (PRS). These scores estimate an individual’s relative genetic predisposition compared with a reference population.

These tests do not necessarily look for a specific “disease-causing mutation.” Instead, they provide information about part of the genetic background that, together with environmental and lifestyle factors, may contribute to overall risk.

Genetic testing for inherited disorders

Genetic testing serves a different purpose when a specific inherited disorder or syndrome is suspected. In this case, the aim is to identify pathogenic or likely pathogenic variants in a specific gene or group of genes known to be associated with the condition in question.

Using modern Next Generation Sequencing (NGS) technologies, multiple genes can be analyzed simultaneously through specialized gene panels or, depending on the clinical question, broader genetic testing can be performed.

Unlike genetic predisposition tests for multifactorial traits, the question here is more targeted: whether a genetic variant is present that could explain or support the diagnosis of a specific inherited condition. The selection of the appropriate test and the interpretation of the results should be carried out in conjunction with the individual and family history and the clinical presentation.

What does a genetic test result mean?

The usefulness of a genetic test depends on the specific question being addressed, the quality of the scientific evidence, and the correct interpretation of the result. Particularly when considering genetic predisposition to complex and multifactorial diseases, a result indicating increased genetic risk:

• does not, by itself, constitute a diagnosis
• does not mean that the disease will develop
• does not determine when or with what severity the disease may manifest
• does not replace individual and family history, clinical assessment, and appropriate laboratory testing

Similarly, a result indicating lower genetic risk does not mean that prevention or monitoring of other risk factors can be disregarded.

Genetic testing provides information about a relatively stable element of the body, DNA. However, to understand what is happening in the body at a given point in time, we also need to assess the changing biological factors that influence health.

From genetic predisposition to the body's functional profile

Genetic information remains largely stable throughout life. In contrast, the body's functional state is constantly changing, influenced by age, diet, physical activity, stress, sleep, environmental exposures, medication use, and other risk factors.

For this reason, knowing an individual’s genetic predisposition represents only one part of the overall assessment of health. Laboratory tests can complement this information by providing insight into the body's current biological and functional state.

Depending on the individual’s history, symptoms, and the purpose of the investigation, different parameters may be assessed, including:

• glucose and insulin regulation and metabolic function more broadly
• the lipid profile and factors associated with cardiovascular risk
• the presence and degree of inflammation or oxidative stress
• the adequacy of vitamins, minerals, and other essential nutrients
• hormonal function and related metabolic markers
• the status of the gut microbiome and selected markers of gastrointestinal function
   

This approach is particularly useful because it assesses factors that, unlike DNA, can change over time and, in many cases, are modifiable. The question therefore shifts from “What conditions am I genetically predisposed to?” to “Are there currently measurable changes associated with this predisposition or with other risk factors?”

Conclusions: Genes Are a Predisposition, Not a Predetermined Outcome

Genes are an important part of our biological identity, but for most complex diseases, they do not determine the course of our health on their own. Genetic predisposition interacts with diet, physical activity, the environment, age, and other factors, many of which can be modified.

For this reason, genetic information has greater practical value when assessed alongside individual and family history, lifestyle, symptoms, and laboratory findings. Two individuals with a similar genetic predisposition may have different functional and metabolic profiles and, therefore, different prevention and monitoring needs.

An individualized assessment allows these different levels of information to be considered together, with the aim of selecting appropriate laboratory tests and identifying factors that are truly relevant to each individual’s health.

References

1. Herrera-Luis E, Benke K, Volk H, Ladd-Acosta C, Wojcik GL. Gene-environment interactions in human health. Nat Rev Genet. 2024;25(11):768-784. doi:10.1038/s41576-024-00731-z
2. Wu H, Eckhardt CM, Baccarelli AA. Molecular mechanisms of environmental exposures and human disease. Nat Rev Genet. 2023;24(5):332-344. doi:10.1038/s41576-022-00569-3
3. Virolainen SJ, VonHandorf A, Viel KCMF, Weirauch MT, Kottyan LC. Gene-environment interactions and their impact on human health. Genes Immun. 2023;24(1):1-11. doi:10.1038/s41435-022-00192-6
4. Roberts E, Flaum N, Evans DG. Clinical implementation of polygenic risk scores. Eur J Hum Genet. Published online September 29, 2025. doi:10.1038/s41431-025-01931-9

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