Genetic testing has come a long way in predicting the risk of common diseases, but knowing what to do with that information can still be challenging. Let’s break down the two main types of genetic tests, how they work, and who benefits most from them.
1. Polygenic Tests (PRS)
A polygenic test analyzes hundreds or thousands of genetic variants across your genome to estimate your overall risk for complex diseases, such as heart disease or diabetes. These diseases are influenced by many genes and environmental factors.
- How it works: It calculates a polygenic risk score (PRS) that compares your genetic risk to the general population.
- Example: A polygenic test for heart disease might show you have a higher genetic risk than average, even if no one in your family has had heart issues. This score is not definitive but provides a broader picture of your genetic susceptibility. A PRS risk of 99 means: using the model they used to develop the test, 99% people had lower risk than you do. It does not mean you have 99% chance of developing the disease.
- When to use: Polygenic tests are useful for conditions where multiple genes and environmental factors play a role. It can also identify those at risk even if they don’t have a family history. Mostly helpful in prevention of diseases.
2. Specific Genetic Tests
In contrast, specific genetic tests focus on specific genes that have a strong link to particular diseases, especially if there is a strong family history of that condition.
- How it works: The test targets mutations in certain genes that are known to directly influence disease risk.
- Example: A BRCA1 or BRCA2 test is used to assess the risk of breast cancer, specifically looking for mutations that significantly increase risk. This test is especially useful if you have a family history of breast or ovarian cancer. More than 60% women with BRCA1 or 2 gene mutation will develop breast cancer in their lifetime. This is much higher than 13% lifetime risk of breast cancer in the general population.
- When to use: Specific genetic tests are typically used when there’s a strong family history of a disease, allowing for targeted preventive care like preventive mastectomy, oophorectomy or intense screening.
Key Differences Between Polygenic and Specific Genetic Tests:
Polygenic Test | Specific Genetic Test |
Analyzes hundreds or thousands of small genetic variations. | Focuses on mutations in known high-risk genes |
Provides an overall risk score compared to the general population | Provides a more precise risk factor for specific diseases |
Helps understand genetic risk for common diseases like heart disease, atrial fibrillation, Alzheimer's dementia, even if you don't have family history of the condition | Best for individuals with a strong family history of a disease |
Examples of Specific Genetic Testing:
1. Familial Hypercholesterolemia (FH) – LDLR, APOB, PCSK9 Genes
- Condition: High cholesterol from birth, leading to early-onset heart disease.
- Why it matters: Family members can be tested and treated early, preventing heart disease.
- Example: If your father had a heart attack in his 40s due to FH, testing can help identify other family members at risk. However, testing cholesterol levels can help one understand the risk as well, as most people with this genetic mutation will have extremely high levels of bad cholesterol.
2. Hypertrophic Cardiomyopathy (HCM) – MYH7, MYBPC3 Genes
- Condition: Thickened heart muscle, increasing risk of sudden cardiac death.
- Why it matters: Genetic testing can determine if frequent heart screenings (echocardiograms) are necessary.
- Example: If your sibling has HCM, and the specific known genetic mutation, testing can help determine whether you can bypass regular heart monitoring with echocardiogram. If your test is negative, you simply aren’t at risk and don’t need regular surveillance echocardiograms.
3. Hereditary Transthyretin Amyloidosis (hATTR) – TTR Gene
- Condition: Protein buildup in the heart and nerves, leading to heart failure and neuropathy.
- Why it matters: Early diagnosis and new treatments can slow disease progression.
- Example: If a family member has hATTR, screening other relatives can help early detection, start treatment and prevent severe symptoms, thereby improving quality of life.
4. Marfan Syndrome – FBN1 Gene
- Condition: Connective tissue disorder that can cause life-threatening aneurysms in the aorta.
- Why it matters: Early detection can prevent sudden death from an aortic rupture.
- Example: If a relative died from a sudden aortic rupture, genetic testing could save lives by detecting the condition in other family members, who can then undergo screening for aortic aneurysm.
5. BRCA1 & BRCA2 – Breast and Ovarian Cancer
- Condition: Mutations increase the risk of breast and ovarian cancer.
- Why it matters: Preventive strategies, like mastectomy or oophorectomy, can reduce cancer risk.
- Example: Angelina Jolie underwent a preventive mastectomy after testing positive for a BRCA mutation, significantly lowering her cancer risk.
Who Should Get Specific Genetic Testing?
Genetic testing is particularly beneficial for individuals with a family history of certain diseases. Here are some groups who may benefit most from genetic testing:
- Multiple family members with the same type of cancer (e.g., breast cancer or colon cancer).
- Those from high-risk ethnic groups (e.g., Ashkenazi Jewish heritage for BRCA mutations).
- Individuals with a known genetic mutation in the family.
- People interested in preventive surgeries to reduce cancer risk (e.g., mastectomy, oophorectomy).
- If a family member has a gene linked to a condition like hypertrophic cardiomyopathy, you might be tested to see if frequent heart screenings are necessary.
Who should get Polygenetic risk screening-
Young individuals who are highly motivated and either lack a family history of common chronic diseases or are unaware of it due to adoption, and who are interested in adopting lifestyle changes or taking medication to lower the risk of developing these diseases in the future.
Important Considerations:
1. Genetic Variants and Risk:
A positive genetic test doesn’t guarantee that you will develop the disease. It simply indicates a higher risk, which means you might need closer follow-up and regular screenings.
2. Negative or Uncertain Results:
A negative test doesn’t completely rule out an inherited condition. It just means the tested genes are not responsible. New genetic discoveries could provide answers in the future.
3. Polygenic Risk Scores (PRS):
A PRS test estimates your relative risk for a disease, but it’s not a guarantee of disease development. For instance, even in the top percentile for coronary artery disease risk, only 16% of people develop the disease by middle age. Other factors like lifestyle, environment, and healthcare access play significant roles. Also PRS was developed using data primarily from individuals of European ancestry- it may not be applicable to all races, although recently effort is being made to make the date more inclusive.
4. GINA (Genetic Information Nondiscrimination Act):
GINA protects you from discrimination by health insurers based on genetic test results. However, it does not apply to life insurance, disability insurance, or long-term care insurance.
Conclusion: DNA Isn’t Destiny
Genetic testing provides valuable insights into your health, but it doesn’t dictate your future. While polygenic tests offer a broad risk assessment and specific tests can pinpoint targeted risks, lifestyle choices and other factors also play a crucial role in disease prevention.
If you’re considering genetic testing, talk to your doctor about which test is right for you based on your family history, health goals, and risk factors. Genetics is only part of the equation—your choices can help shape your health future.
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