Apr 9, 2019 - Health + Traits

Report Brings to Light Underdiagnosed Condition

Senior black man sitting on grass, embraced by his grandson

Today, 23andMe added a new report on TTR-related hereditary amyloidosis, a genetic, multi-system disease.

What is TTR-Related Amyloidosis?

This new Genetic Health Risk report looks at three of the most common genetic variants associated with TTR-related hereditary amyloidosis. This little-known and underdiagnosed genetic condition is caused by the buildup of a protein called transthyretin (TTR) in the body’s tissues and organs. This protein buildup can damage the nerves, heart, and other body parts. Symptoms vary widely, but can include cardiomyopathy, peripheral neuropathy and autonomic neuropathy. Because symptoms of TTR-related hereditary amyloidosis can vary widely, it is often misdiagnosed.[1]  

23andMe’s new report gives customers an opportunity to learn about their potential risk for TTR-related hereditary amyloidosis so that they can take action by speaking to their doctor to learn more about their risk and discuss appropriate next steps, which may include diagnostic testing.

Alnylam Collaboration

Based on a shared commitment to disease awareness of TTR-related hereditary amyloidosis, Alnylam Pharmaceuticals supported the publication of this report in part. Alnylam has worked with TTR-related hereditary amyloidosis patients for years and has a deep understanding of how the condition can impact individuals and their families. As such, the company’s scientific and medical teams provided input on information related to the condition, including its symptoms and how it manifests in the patient community.

To further the goal of awareness and early detection, 23andMe will also be running an awareness program in collaboration with Alnylam to provide 23andMe Health + Ancestry Service kits to first-degree relatives—parents, full siblings, and adult children—of any 23andMe customer with an identified TTR variant. Hopefully, this effort will increase awareness and lead to earlier diagnosis of this condition. The program will be launched later this year.

Report Details

The new report looks at three of the most common TTR variants that account for an estimated 50-to-80 percent of TTR-related hereditary amyloidosis cases.[2]

The report does not test for all possible variants linked to TTR-related hereditary amyloidosis. Customers who do not have one of the variants 23andMe tests for could still have a variant not covered in the report.

The three variants in this report—V122I, V30M, and T60A—each occur at different frequencies among people of different ethnicities.

Facts to Keep in Mind

However, it’s important to remember that not everyone who inherits one of these variants will necessarily develop symptoms.

  • The V122I variant is most common in African Americans and people of West African descent. Most people with this variant have some amount of TTR protein buildup in the heart after age 60, but not all will end up with heart damage. Approximately 10 percent of African Americans over the age of 60 with congestive heart failure likely carry this variant.[3]
  • The V30M variant is most common among people of Portuguese, Northern Swedish, and Japanese descent but carries different risks for each ethnicity. About 50 percent of people of Northern Swedish descent with this variant develop TTR-related hereditary amyloidosis by the age of 80, with symptoms often appearing after the age of 60. By comparison, about 90 percent of people of Portuguese descent with the V30M variant develop the condition by age 80, with symptoms appearing as early as 20-30 years of age. People of Japanese descent with the V30M variant can develop symptoms as early as their 20s or as late as their 90s, depending on family history.[4] [5]
  • The T60A variant is most common in people of Irish descent. It is also found in people of British descent. People with this variant typically develop symptoms between 45 and 80 years old. Lifetime risk estimates are not available for people with this variant.[6]

Prevalence and Treatment

While the condition is little known and underdiagnosed, the frequency of TTR variants among certain ethnicities is relatively significant.

Estimates suggest that 1 in 28 African Americans, 1 in 67 people from Northern Sweden, 1 in 90 people from Northwest Ireland, and 1 in 625 people of Portuguese descent have one of the three variants included in 23andMe’s new report. However, there are no current estimates on how many of those with one of the three variants will go on to develop TTR-related hereditary amyloidosis.

This report, like 23andMe’s other Genetic Health Risk reports, aims to give customers an opportunity to learn of a potential health risk so that they can work with their health care provider on the best options for mitigating and managing that risk.

Treatments for TTR-related hereditary amyloidosis include the use of medications or surgical intervention to address the symptoms. Recently approved medications are now being used to decrease the production of the TTR protein. In addition, because the liver produces most of the TTR protein, some patients have benefited from liver transplants. Additional research on developing new treatment options is also currently underway.

23andMe Health + Ancestry Service customers who are on the most recent genotyping platforms can find this new report in the Health Predisposition section of their account. Not yet a customer? You can find out more about 23andMe’s Health + Ancestry Service here.


[1]Sekijima Y et al. (2001). “Familial Transthyretin Amyloidosis.” [Updated 2018 Dec 20].
[2] Gertz MA et al. (2015). “Diagnosis, Prognosis, and Therapy of Transthyretin Amyloidosis.” J Am Coll Cardiol. 66(21):2451-2466.
[3] Buxbaum JN et al. (2017). “Transthyretin V122I (pV142I)* cardiac amyloidosis: an age-dependent autosomal dominant cardiomyopathy too common to be overlooked as a cause of significant heart disease in elderly African Americans.” Genet Med. 19(7):733-742.
[4] Holmgren G et al. (1994). “Geographical distribution of TTR met30 carriers in northern Sweden: discrepancy between carrier frequency and prevalence rate.” J Med Genet. 31(5):351-4.
[5] Planté-Bordeneuve V et al. (2003). “Genetic study of transthyretin amyloid neuropathies: carrier risks among French and Portuguese families.” J Med Genet. 40(11):e120.
[6] Reilly MM et al. (1995). “Familial amyloid polyneuropathy (TTR ala 60) in north west Ireland: a clinical, genetic, and epidemiological study.” J Neurol Neurosurg Psychiatry. 59(1):45-9.

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