What can 23andMe results tell you about your cholesterol-related risks?

A few months back, 23andMe announced that it had added variants related to Familial Hypercholesterolemia (FH) to its Genetic Health Risk Report.

If you’ve ordered 23andMe’s Health + Ancestry test, what will these results tell you about your cholesterol risk?

For most people—the answer is (once again) not too much!

A personal or family history of high cholesterol is relatively common in the United States. Genetics, environmental factors and lifestyle (diet and exercise) all play a role. But for most of us, the genetic component is spread across a number of different genes (polygenic). Available genetic testing at this point isn’t great at testing for polygenic risk. (Some people think this is where genetic testing is headed and we should embrace it…. And others disagree.)

What is FH… and what are the chances that I have it?

For a minority of individuals (about 1 in 250 in the general population), a personal or family history of high cholesterol (LDL-C) is actually tied to one mutation in a particular gene (APOB, LDLR, or PCSK9). Integrating appropriate testing for Familial Hypercholesterolemia (along with BRCA and Lynch syndrome) into public health practice has long been a priority of the CDC’s Office of Public Health Genomics (OPHG).

If you have a personal and/or family history of high cholesterol, your chance of having Familial Hypercholesterolemia would be Higher than 1 in 250. A family history of heart attacks or strokes, especially at a young age is a sign that this could be FH!  According to National Lipid Association guidelines, genetic testing for FH should be considered if untreated fasting LDL cholesterol is at or above 190 mg/dL.

If you have a personal or family history of high cholesterol, will this test be helpful for you?

Possibly–but probably not, simply because 23andMe is only reporting on 24 of >2000 different possible mutations related to Familial Hypercholesterolemia. If you have a Positive result, that’s valuable. But if you have a Negative test result and a significant personal or family history of high cholesterol–that’s still a reason to consider more comprehensive genetic testing related to Familial Hypercholesterolemia.

If you have no known family history of high cholesterol, will this test be helpful for you?

Possibly! Many of us are unaware of our own cholesterol levels, let alone the cholesterol levels of family members. This new reporting by 23andMe could help to identify a few more of these individuals. FH is undiagnosed in an estimated 90% of individuals who have it! If you have a positive test result, seek out genetic counseling and follow up with your doctor.

What would a diagnosis of FH mean for family members?

FH is typically inherited in an autosomal dominant manner. A mutation in just one copy of an FH-related gene is sufficient to cause FH. With each pregnancy, there is a 50% chance of passing down this mutation. Identifying a mutation in a family member can be incredibly valuable in then identifying other family members who

1) also have FH and should have their cholesterol monitored starting at a young

   age–which can be lifesaving

2) do Not have FH and likely have average cholesterol-related risks–despite

   family history.

Some people do have two FH-related mutations (Homozygous FH). Individuals with Homozygous FH usually have extremely high cholesterol levels from a young age and are more likely to have a more striking family history of heart attacks or strokes. To hear directly from an individual with Homozygous FH, check out our Patient Stories podcast episode with Colleen McCready. And watch for another FH-related interview that will be out next week!

Wish you could talk to a genetics expert?

Grey Genetics has a growing Network of Genetic Counselors available for telehealth appointments, including several with expertise in cardiovascular genetics. You can book an appointment online for a time that’s convenient for you. A genetic counselor can help you make sense of genetic testing options and results within the context of your own personal and family health history. A genetic counselor can also help you understand the implications of test results not only for your own health, but also for that of family members.

Are you a DIY-er but just want a little more guidance?

Grey Genetics has developed new services for individuals who are looking for some more guidance but prefer a lower cost option or just prefer not to talk with someone one-on-one at this point. Check them out and see if one of these services is for you!  

Further Reading & Quality News Coverage

23andMe Offers a New Report on Familial Hypercholesterolemia. 23andMe Blog. February  20, 2019.
Khera, A., et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations.” Nature Genetics. 50: 1219–1224. August 2018.

Curtis, David. Clinical relevance of genome-wide polygenic score may be less than claimed.” Annals of Human Genetics, March 25, 2019.

Goldberg, Ann C., et al. Familial Hypercholesterolemia: Screening, diagnosis and management of pediatric and adult patients. National Lipid Association. 2011.

Landucci, Kelly. A Not-So Rare Disease: Coronary Heart Disease.” Grey Genetics News Corner.

Williams, Nori. Hello February: Heart Month from the Perspective of a Cardiovascular Genetic Counselor.” Grey Genetics News Corner.

The FH Foundation  


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