Key Takeaways
|
September is National Cholesterol Education Month, and September 24 is Familial Hypercholesterolemia (FH) Awareness Day. Together they make this a good time to ask a question that standard cholesterol testing does not answer: why is your number the way it is?
Same Number, Two Very Different Stories
A standard lipid panel measures how much cholesterol is circulating in your blood right now. It is a snapshot, and a useful one. About 55% of people in the U.S. will develop high cholesterol by their 70s, and high LDL (sometimes called “bad cholesterol”) raises the risk for heart disease, stroke and peripheral artery disease. Because high LDL usually causes no symptoms at first, regular screening matters.
What your lab results cannot tell you is the reason behind your number. For most people with high cholesterol, the cause is complex. Thousands of common genetic variants each nudge LDL levels slightly upward, and those small effects combine with diet, activity, age, weight, pregnancy, other health conditions and certain medications leading to your LDL level. Change the modifiable parts of that equation and your LDL often responds.
For a smaller group, the cause is monogenic, meaning a single genetic variant is responsible for most of their LDL level. That is a fundamentally different situation, and it calls for a different response.
When One Gene Does the Heavy Lifting
FH is very high cholesterol that runs in families. Variants in genes including LDLR, APOB and PCSK9 reduce the liver’s ability to clear LDL from the bloodstream. In people with a variant in one of these genes, LDL levels can be elevated from birth rather than creeping up as you age.
That lifetime exposure is what makes FH serious. About 1 in 250 people worldwide have FH, and according to the Family Heart Foundation as many as 70% of them have not been diagnosed. Left untreated, men with FH have roughly a 50% risk of a heart attack by age 50, and women roughly a 30% risk by age 60. Sometimes a heart attack is the first sign of elevated LDL.
Healthy habits still matter for people with FH, but they are usually not enough to lower LDL on their own. Effective treatment typically requires cholesterol-lowering medication alongside lifestyle changes, and starting earlier substantially reduces cardiovascular risk.
FH also travels through families. Each first-degree relative (parents, siblings or children) of someone with FH has at least a 50% chance of having inherited the same variant, often with no outward signs. This is why genetic counselors recommend cascade testing: once one person is diagnosed, close relatives get tested too. It is one of the most effective ways to catch FH early.
What Your Genetics Can Add
23andMe offers a few different windows into cholesterol-related genetics.
- The Familial Hypercholesterolemia Genetic Health Risk report* looks for 24 variants, one in the APOB gene and 23 in the LDLR gene. It does not cover all of the more than 1,000 known FH variants, so a negative result does not rule FH out.
- If you do not have an FH variant, the LDL Cholesterol PRS report* uses a polygenic score built from more than 2,000 genetic markers to estimate your likelihood of developing high LDL cholesterol. This covers more typical, common genetic changes that, combined with diet and lifestyle, can lead to high LDL cholesterol.
- The SLCO1B1 Drug Transport report** covers a variant that affects a protein responsible for transporting statins out of the bloodstream and into the liver. Statins are a commonly prescribed medication used to lower cholesterol. Certain genetic changes in the SLCO1B1 gene are associated with higher chances of experiencing side effects.
None of these diagnose a condition or tell you your cholesterol level today. They can give you and your clinician more context for a conversation.
What You Can Do This Month
- Get a baseline lipid panel if you have not had one recently. Most guidelines recommend adults start in their twenties and repeat every few years.
- Ask your relatives about early heart disease, heart attacks before age 55 in men or 65 in women, or cholesterol that has been high for as long as anyone can remember. These are red flags worth mentioning to your doctor.
- If your numbers stay high despite doing everything right, ask why. A genetic counselor can help you figure out whether genetic testing makes sense.
- Ask about Lp(a) testing. Lipoprotein(a) is a cholesterol-carrying particle that can significantly raise your risk for heart disease. It’s often skipped in routine lab tests. Your Lp(a) levels are largely set by your genetics and stay fairly stable for life, so a single test may be all you need.
Curious what your DNA says about your cholesterol? Review your Familial Hypercholesterolemia Genetic Health Risk report and your LDL Cholesterol PRS report. And if you want to go deeper on how monogenic and complex conditions differ, our Genetics Learning Hub is free and open to everyone.
* The 23andMe PGS test includes health predisposition and carrier status reports. Health predisposition reports include both reports that meet FDA requirements for genetic health risks and PRS reports which are based on a statistical model that includes data and insights from 23andMe consented research participants, and have not been reviewed by the FDA. The test uses qualitative genotyping to detect select clinically relevant variants in the genomic DNA of adults from saliva for the purpose of reporting and interpreting genetic health risks and reporting carrier status. It is not intended to diagnose any disease. Your ethnicity may affect the relevance of each report and how your genetic health risk results are interpreted. Each genetic health risk report describes if a person has variants associated with a higher risk of developing a disease, but does not describe a person’s overall risk of developing the disease. Each PRS report describes if a person has a certain likelihood of developing a condition, but does not describe a person’s overall likelihood. The test is not intended to tell you anything about your current state of health, or to be used to make medical decisions, including whether or not you should take a medication, how much of a medication you should take, or determine any treatment. Our carrier status reports can be used to determine carrier status, but cannot determine if you have two copies of any genetic variant. These carrier reports are not intended to tell you anything about your risk for developing a disease in the future, the health of your fetus, or your newborn child’s risk of developing a particular disease later in life. For certain conditions, we provide a single report that includes information on both carrier status and genetic health risk. The Familial Hypercholesterolemia genetic health risk report is indicated for reporting of one variant in the APOB gene and 23 variants in the LDLR gene and describes if a person has variants associated with an increased risk of developing very high LDL cholesterol, which can lead to heart disease. The majority of the variants included in this report have been most studied in people of European and Lebanese descent, as well as in the Old Order Amish. For important information and limitations regarding each genetic health risk report, visit 23andme.org/shop/test-info/
** 23andMe PGS Pharmacogenetics reports: The 23andMe test uses qualitative genotyping to detect 3 variants in the CYP2C19 gene, 2 variants in the DPYD gene and 1 variant in the SLCO1B1 gene in the genomic DNA of adults from saliva for the purpose of reporting and interpreting information about the processing of certain therapeutics to inform discussions with a healthcare professional. It does not describe if a person will or will not respond to a particular therapeutic. Our CYP2C19 Pharmacogenetics report provides certain information about variants associated with metabolism of some therapeutics and provides interpretive drug information regarding the potential effect of citalopram and clopidogrel therapy. Our SLCO1B1 Pharmacogenetics report provides certain information about variants associated with the processing of some therapeutics and provides interpretive drug information regarding the potential effect of simvastatin therapy. Our DPYD Pharmacogenetics report does not describe the association between detected variants and any specific therapeutic. Results for DPYD and certain CYP2C19 results should be confirmed by an independent genetic test prescribed by your own healthcare provider before taking any medical action. Warning: Test information should not be used to start, stop, or change any course of treatment and does not test for all possible variants that may affect metabolism or protein function. The PGS test is not a substitute for visits to a healthcare professional. Making changes to your current regimen can lead to harmful side effects or reduced intended benefits of your medication, therefore consult with your healthcare professional before taking any medical action. For important information and limitations regarding Pharmacogenetic reports, visit 23andme.org/shop/test-info/pharmacogenetics/
