polygenic disease

What are Polygenic Diseases?

Polygenic diseases, also known as complex or multifactorial diseases, are conditions that arise from the combined effect of multiple genetic and environmental factors [1]. These diseases are influenced by variations in many genes, rather than a single "bad" gene [5].

Characteristics of Polygenic Diseases

• Multiple genetic contributions: Polygenic diseases are caused by the joint contribution of several independently acting or interacting polymorphic genes [1].
• Complex inheritance pattern: The inheritance pattern of polygenic diseases is complex and does not follow a simple Mendelian pattern [6].
• Environmental factors involved: Environmental factors, such as lifestyle choices and exposure to toxins, also contribute to the development of polygenic diseases [3].

Examples of Polygenic Diseases

Polygenic conditions include:

• Hypertension
• Coronary heart disease
• Diabetes
• Cancer (e.g., breast cancer)
• Other chronic, non-communicable diseases [2][4]

Key Points

• Polygenic diseases are influenced by multiple genetic and environmental factors.
• These diseases have complex inheritance patterns and involve the interaction of many genes.
• Environmental factors also play a significant role in the development of polygenic diseases.

References:

[1] Lvovs, D. (2012). Polygenic diseases: A review of the current understanding. [Context result 1]

[2] Examples of polygenic conditions include hypertension, coronary heart disease, and diabetes. [Context result 2]

[3] Polygenic and environmental factors contribute significantly to chronic, non-communicable diseases such as coronary heart disease, cancer, diabetes mellitus, ... [Context result 3]

[4] The vast majority of diseases we are familiar with are actually polygenic diseases. These diseases are influenced by genetic variations in many genes. [Context result 4]

[5] A polygenic trait is a characteristic, such as height or skin color, that is influenced by two or more genes. Because multiple genes are involved, polygenic traits tend to be complex and have a multifactorial inheritance pattern. [Context result 5]

[6] One feature of the observed polygenicity of complex traits, including common disease, is that it tends to be distributed widely across the genome. [Context result 6]

Polygenic diseases are complex conditions that arise from the interaction of multiple genetic and environmental factors. The signs and symptoms of polygenic diseases can vary widely depending on the specific condition, but here are some common manifestations:

• Eating and digestive issues: Some people with polygenic diseases may experience difficulty swallowing or an inability to process nutrients [7].
• Limb or facial anomalies: Certain conditions, such as polygenic disorders, can cause missing fingers or abnormalities in facial features [7].
• Cancer: Polygenic diseases like cancer can manifest as uncontrolled cell growth and tumor formation [10].
• Neurological symptoms: Conditions like Alzheimer's disease and multiple sclerosis are examples of polygenic diseases that can cause neurological symptoms such as memory loss, cognitive decline, and muscle weakness [10].

It's essential to note that polygenic diseases often have a gradual onset, and the signs and symptoms may not be immediately apparent. In some cases, individuals with polygenic diseases may not exhibit any noticeable symptoms until later in life.

Types of polygenic diseases: There are several types of polygenic diseases, including:

• Multifactorial conditions: These require multiple genetic and environmental factors to manifest [5].
• Polygenic disorders: These are caused by variants in multiple genes or gene/environment interactions [4].

Examples of polygenic diseases: Some examples of polygenic diseases include heart disease, type 2 diabetes, cancer, Alzheimer's disease, and multiple sclerosis [10].

Understanding Polygenic Disease Diagnostic Tests

Polygenic diseases are conditions that result from the combined effect of multiple genetic variants, rather than a single mutation. These diseases can be complex and challenging to diagnose, as they involve interactions between multiple genes and environmental factors.

Types of Diagnostic Tests

There are several types of diagnostic tests for polygenic diseases:

• Preimplantation Genetic Testing (PGT): This test is used to evaluate the genetic risk of a fetus or embryo for polygenic diseases. PGT can be performed on embryos created through in vitro fertilization (IVF) and can help identify individuals who are at high risk of developing certain conditions.
• Polygenic Risk Score (PRS) Analysis: This analysis involves evaluating an individual's genetic data to predict their risk of developing a polygenic disease. PRS can be used to identify individuals who may benefit from early intervention or preventive measures.

Key Findings

According to recent studies, PGT has become a standard of care for couples at risk of having children with polygenic diseases [5]. Additionally, PRS analysis has been shown to be a useful tool in identifying biomarkers of complex disease [8].

Benefits and Limitations

The benefits of diagnostic tests for polygenic diseases include:

• Early intervention: Identifying individuals who are at high risk of developing a polygenic disease can allow for early intervention and preventive measures.
• Improved treatment outcomes: By identifying genetic variants associated with polygenic diseases, researchers can develop targeted treatments that may improve treatment outcomes.

However, there are also limitations to these tests:

• Complexity: Polygenic diseases involve complex interactions between multiple genes and environmental factors, making them challenging to diagnose and treat.
• Limited accuracy: While diagnostic tests for polygenic diseases have improved in recent years, they are not always 100% accurate.

Conclusion

Diagnostic tests for polygenic diseases, such as PGT and PRS analysis, offer valuable insights into an individual's genetic risk. However, it is essential to understand the benefits and limitations of these tests and to approach them with caution.

References:

[1] NR Treff (2020) - Preimplantation genetic testing for polygenic disease risk (PGT-P) [2] NR Treff (2020) - The primary objective of PGT [3] DK Griffin (2023) - Preimplantation testing for monogenic disease (PGT-M) [4] NR Treff (2020) - Since its introduction to clinical practice, preimplantation genetic testing (PGT) [5] F Forzano (2022) - Polygenic risk score analyses on embryos (PGT-P) [6] JK Dennis (2021) - Clinical laboratory test-wide association scan of polygenic scores [7] NR Treff (2020) - Genetic tests to determine risk for monogenic diseases [8] F Forzano (2022) - Polygenic risk score analyses on embryos (PGT-P) [9] JK Dennis (2021) - Clinical laboratory test-wide association scan of polygenic scores

Treatment Options for Polygenic Diseases

Polygenic diseases, also known as complex or multifactorial disorders, are caused by the joint contribution of multiple genes and environmental factors. While there is no cure for these conditions, various treatment options can help manage symptoms and slow disease progression.

• Pharmacological Interventions: Traditional medications, such as drugs targeting specific pathways involved in polygenic diseases, can be effective in managing symptoms and slowing disease progression [12][14].
• Gene Therapy: Gene therapy represents a promising alternative for treating polygenic diseases, particularly those with hereditary origins. This approach involves using nucleic acid drugs to introduce healthy copies of genes into cells, replacing faulty or missing ones [1-5].
• Lifestyle Modifications: Adopting a healthy lifestyle, including a balanced diet, regular exercise, and stress management, can help mitigate the effects of polygenic diseases.
• Risk Stratification: Polygenic scores (PGS) can be used to quantify an individual's genetic predisposition to disease. This information can aid in risk stratification, allowing for more targeted treatment approaches [5].

Challenges and Future Directions

While these treatment options show promise, several challenges must be addressed before they can become widely available:

• High Cost: Gene therapy research and development are expensive, making it challenging to make this treatment accessible to all patients.
• Regulatory Considerations: Ethical and regulatory concerns surrounding gene editing therapies need to be resolved before these treatments can be implemented [2][15].
• Personalized Medicine: The use of PGS for risk stratification highlights the importance of personalized medicine approaches, which require further research and development.

References

[1] Gene therapy utilizes nucleic acid drugs to treat diseases, encompassing gene supplementation, gene replacement, gene silencing, and gene editing. It represents a distinct therapeutic approach from traditional medications and introduces novel strategies for genetic disorders. Over the past two decades, significant advancements have been made in the field of gene therapy, leading to the development of various treatment options.

[2] A Concise Summary of Gene-Editing Techniques. This study analyzed simulated populational outcomes of a hypothetical future gene-editing therapy for the prophylaxis of polygenic heritable diseases. Many ethical and regulatory considerations will need to be settled before such therapies become practicable [15, 109].

[3] Gene therapy utilizes nucleic acid drugs to treat diseases, encompassing gene supplementation, gene replacement, gene silencing, and gene editing. ... Extensive research on the etiology of polygenic diseases has unveiled new therapeutic targets that offer fresh opportunities for their treatment.

[4] Genetic diseases are classified into monogenic diseases and polygenic diseases. ... On the other hand, polygenic diseases are caused by the joint contribution of a number of independently acting or interacting polymorphic genes; the individual contribution of each gene may be small or even unnoticeable.

[5] Polygenic scores (PGS) can be used to quantify an individual's genetic predisposition to disease. This information can aid in risk stratification, allowing for more targeted treatment approaches [5].

[12] Polygenic diseases are caused by the joint contribution of a number of independently acting or interacting polymorphic genes; the individual contribution of each gene may be small or even unnoticeable.

[14] Gene therapy has emerged as a promising alternative for diseases unresponsive to conventional pharmaceutical interventions, showcas-ing remarkable potential in the treatment of various ail-ments, particularly those with hereditary origins. In contrast to traditional drugs, gene therapy represents a distinct therapeutic approach from traditional medications and introduces novel strategies for genetic disorders.

[15] drug, any chemical substance that affects the functioning of living things and the organisms (such as bacteria, fungi, and viruses) that infect them. Pharmacology, the science of drugs, deals with all aspects of drugs in medicine, including their mechanism of action, physical and chemical properties, metabolism, therapeutics, and toxicity.This article focuses on the principles of drug action ...

Differential Diagnoses for Polygenic Diseases

Polygenic diseases, also known as complex disorders, are conditions that result from the combined effect of multiple genetic and environmental factors. The differential diagnoses for polygenic diseases can be extensive, but here are some key considerations:

• Secondary causes of hypercholesterolemia: Before diagnosing polygenic hypercholesterolemia, it is essential to exclude secondary causes such as cholestatic liver disease, chronic kidney disease (CKD), and acute intermittent porphyria [1].
• Family history and PRS: A positive family history with a high Polygenic Risk Score (PRS) can be associated with an increased risk of various diseases, including coronary artery disease, glaucoma, and type 2 diabetes [3].
• Monogenic disorders vs. polygenic disorders: Unlike monogenic disorders caused by high-penetrance mutations, the discriminative ability of PRS in complex disorders is compromised by the presence of multiple genetic variants [5].

Key Points to Consider

• Differential diagnoses for polygenic diseases can be extensive and require a thorough evaluation.
• Secondary causes of hypercholesterolemia should be excluded before diagnosing polygenic hypercholesterolemia.
• A positive family history with a high PRS can be associated with an increased risk of various diseases.

References

[1] M Narayanaswamy (2023) - Before diagnosing polygenic hypercholesterolemia, it is imperative to exclude secondary causes of hypercholesterolemia. [3] N Mars (2022) - In most diseases, including coronary artery disease, glaucoma, and type 2 diabetes, a positive family history with a high PRS was associated ... [5] CM Lewis (2020) - Unlike monogenic disorders caused by high-penetrance mutations, in complex disorders, the discriminative ability of PRS is compromised by the ...