Key points
- Your genetic counselor, lipid specialist, or other healthcare provider might recommend genetic testing for familial hypercholesterolemia (FH) if you have high cholesterol and a family history of early coronary artery disease or heart attacks.
- Finding a genetic change is not required for diagnosing FH, but it allows family members to be checked for the same genetic change.
Why get tested
Your lipid specialist or other healthcare provider may refer you for genetic counseling and testing for familial hypercholesterolemia (FH) if they suspect that you have FH based on your blood cholesterol levels, family health history of early coronary artery disease or heart attacks, and physical signs of FH. Another reason for referral is having a family member with FH.
Genetic testing for FH can confirm your diagnosis, help you better understand your risk for coronary artery disease and heart attacks, and inform your treatment. If genetic testing shows that you have a genetic change that causes FH, your family members can be tested for the same change to find out if they have FH.
Considerations for testing
Genetic testing for familial hypercholesterolemia (FH) looks for inherited genetic changes known to cause FH, most commonly in the LDLR, APOB, PCSK9, and LDLRAP1 genes.12 If possible, the first person tested in your family should be someone with signs of FH. If the FH-causing genetic change that runs in your family is known, you should be tested for that genetic change.
Genetic testing finds the genetic change causing FH in about 60%–80% of people thought to have FH. Some genetic changes that cause FH remain unknown. This means that some people with FH will have a genetic change that is not found through genetic testing. However, finding a genetic change is not required for diagnosing FH. Note that most people with a personal or family history of heart disease or high blood cholesterol do not have FH, so genetic testing will not help them.
Testing results
Your lipid specialist or genetic counselor can help you understand your test results. Interpretation of genetic testing results may differ, depending on whether or not someone in your family has already had an FH-causing genetic change found through genetic testing.
If no known FH-causing genetic change
What genetic testing results mean for you and your family if the following both apply:
- You show signs of FH or have a strong family history of heart disease.
- No one in your family has already had an FH-causing genetic change found through genetic testing.
Positive test result
The test showed that you have a genetic change known to cause FH.
What it means for you
- Medical options are available to reduce your risk of heart disease.
What it means for your family
- Family members who have genetic testing should get tested for the same genetic change you have.
Negative test result with LDL cholesterol lower than 190 mg/dL
The test did not find a genetic change that is known to cause FH.
What it means for you
- Results are considered uninformative. If a genetic change runs in your family, the negative result could mean that you did not inherit the genetic change. However, it could also mean that the genetic change that runs in your family was not included in the test you had.
- You are still considered at increased risk for heart disease that runs in your family. Talk to your doctor about steps you can take to prevent heart disease.
What it means for your family
- Testing might still be recommended for family members who show signs of FH.
Negative test result with LDL cholesterol higher than 190mg/dL
The test did not find a genetic change that is known to cause FH.
What it means for you
- Finding a genetic change is not required for an FH diagnosis. About 20-40% of people with FH have negative genetic testing results.
- Your cholesterol levels, family health history, and physical signs can be enough for an FH diagnosis.
- If you have FH, medical options are available to reduce your risk of heart disease.
What it means for your family
- Genetic testing in your family members is unlikely to be helpful unless another family member has FH or a known FH genetic change.
- Family members can still be checked using cholesterol measurements and physical exams.
Variant of uncertain significance (VUS) result
The test found a genetic change in one of the genes related to FH, but whether that specific genetic change causes FH is unknown.
What it means for you
- You are still considered at risk if heart disease runs in your family.
- You could still be diagnosed with FH depending on your cholesterol levels, family health history, and physical signs.
- If you have FH, medical options are available to reduce your risk of heart disease.
What it means for your family
- Family members typically should not be tested for a VUS until we learn whether or not it causes FH
If known FH-causing genetic change
What genetic testing results mean for you and your family if you were tested for an FH-causing genetic change that had previously been found in your family.
Positive test result
You have the FH genetic change that runs in your family.
What it means for you
- Medical options are available to reduce your risk of heart disease.
What it means for your family
- Family members who have genetic testing should get tested for the same genetic change you have.
Negative test result with LDL cholesterol lower than 190 mg/dL
You do not have the genetic change that runs in your family.
What it means for you
- You are not at higher risk for high cholesterol than the average person.
- You cannot pass the genetic change on to your child.
- If you have LDL cholesterol levels higher than 100 mg/dL, you may be at risk for heart disease from other factors.
What it means for your family
- Your children cannot inherit the genetic change that runs in your family and do not need to be tested.
- Other family members could still inherit the genetic change and should be tested for the genetic change that runs in your family.
Negative test result with LDL cholesterol higher than 190 ml/dL
You do not have the genetic change that runs in your family.
What it means for you
- Your high cholesterol levels are not due to the FH-causing genetic change that runs in your family.
- You might have a different FH genetic change and further testing might be needed.
- If you have FH, medical options are available to reduce your risk of heart disease.
What it means for your family
- Other family members could still inherit the genetic change and should still be tested for the genetic change that runs in your family.
- Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel. J Am Coll Cardiol. 72:662-680. Sturm AC et al. 2018.
- International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia. Nat Rev Cardiol. 20:845-869. Watts et al. 2023.