Health at 23andMe: What’s Your Status?

While many health conditions are complex and influenced by a combination of genetic and non-genetic factors, others follow a much simpler pattern where disruptions (or “mutations”) in a single gene can directly cause disease. These diseases are often referred to as Mendelian diseases, named after the monk (Gregor Mendel) who discovered the concept of genes and simple genetic inheritance using experiments in pea plants. At 23andMe, you can learn whether you “carry” certain mutations linked to a number of Mendelian diseases with the Carrier Status reports. But what does it mean to be a carrier?

Recall that all of us have two copies of each chromosome — one from mom and one from dad — and, therefore, have two copies of each gene. If both copies of a gene turn out to be impaired and that gene is important for health or development, disease results. Sometimes, having just one working copy of a gene is OK — in this case, people are usually perfectly healthy, and simply “carry” an impaired copy of the gene. If two carriers start a family, however, each child has a 25% chance of inheriting two impaired copies and being affected with the disease. (See sidebar below for more information about inheritance patterns for Mendelian diseases.)

23andMe’s Carrier Status reports identify whether you carry any of a set of mutations for each of 24 different genetic diseases*. Most of the time, your results will show “Variant Absent” — and this is a good thing! It means you do not carry any of the genetic variants that 23andMe tests for that disease.

You might also see a few of your results listed as “Variant Present,” meaning you are a carrier for a variant tested by 23andMe for that disease. Don’t worry — this is not always uncommon. For example, one out of 29 people with European ancestry in the United States carries a variant linked to cystic fibrosis (the numbers are one out of 46, one out of 64, and one out of 90 for Hispanic Americans, African Americans, and Asian Americans, respectively). Carrier status information can, however, be useful for those planning to have children.

Like the Disease Risk reports, each Carrier Status report has background information about the disease in the “How It Works” tab and more details about the variants tested in the “Technical Report” tab, both located under the title of the report. Instead of the Odds Calculator, however, the section under “Your Genetic Data” contains a table with your carrier status results for that disease (click to enlarge images).

My results for Canavan disease My results for cystic fibrosis

 

Most of the reports will have tables similar to the one on the left for Canavan Disease: you either have no copies of any genetic variants tested that are associated with Canavan Disease, one copy, or multiple copies (and therefore have Canavan Disease). Other diseases are slightly more complicated in that some genetic variants might not result in the same severity of disease. In the case of Cystic Fibrosis, shown on the right, there are some genetic variants that do not always cause disease, and some that cause more severe disease than others. One variant in particular is well-known to cause “classic” cystic fibrosis in people with two copies of it.

Types of Mendelian diseases

  • Autosomal recessive – The gene involved resides on one of the 22 non-sex chromosomes (known as “autosomes). Two mutations impairing the gene (one on each copy of the chromosome) are required to cause the disease. Examples are cystic fibrosis, Tay-Sachs disease, and sickle cell anemia. Sometimes, carriers may have a mild form of the disease, with or without overt symptoms; this is the case with sickle cell anemia.
  • Autosomal dominant – The gene involved resides on one of the 22 non-sex chromosomes. One mutation impairing the gene may be sufficient to cause disease. Examples are familial hypercholesterolemia and Marfan syndrome.
  • X-linked recessive – The gene involved resides on the X chromosome. Two mutations impairing the gene (one on each copy of the chromosome) are required to cause the disease in women. Because men only have one copy of the X chromosome, one mutation is sufficient to cause the disease in men. X-linked recessive diseases are more common in men than in women for this reason. A well-known example is hemophilia.

X-linked dominant, Y-linked, and mitochondrial diseases also exist but they are fewer and more rare.

Online Mendelian Inheritance in Man (OMIM) is a publicly available catalog of Mendelian disease information.

One special case in the Carrier Status category is Hemochromatosis, a disease that results from mutations in a gene that regulates iron absorption in the body. This is a fairly common genetic disease and many people with European ancestry will be carriers of one of the two mutations that 23andMe tests. It turns out that of those who have two copies of a disease-associated variant, few (30% of men and about 1% of women) will actually develop iron overload, the primary symptom of the disease.

Note that while the Carrier Status reports do tell you if you have two copies of a disease-associated variant, it is very rare for someone to receive that result for most of the diseases due to their extreme rarity. (In these cases, it is even more unlikely for someone to be surprised by such a result, since you would almost certainly already know that you have the disease.) The main function of these reports, therefore, is to inform you of your status as a carrier or non-carrier for the genetic variants tested.

For some populations, this information is especially useful. People with Ashkenazi Jewish ancestry have a higher chance of carrying genetic variants associated with certain diseases, including Tay-Sachs and Canavan disease. Sickle cell anemia is more common in those with African ancestry. And cystic fibrosis is one of the more common genetic diseases in populations with European ancestry. If you do turn out to be a carrier for something, you can learn more about which variant you carry in the Technical Report.

23andMe encourages people who are concerned about these diseases or considering starting a family to discuss their results with a genetic counselor. 23andMe collaborates with Informed Medical Decisions, Inc., to give customers direct access to independent, board-certified genetic counselors that have been specifically trained in 23andMe’s reports.

Keep in mind that while 23andMe tests for the most common genetic variants associated with each genetic disease, there are many other disease-causing variants that are not tested. Though it is very unlikely, it is possible for someone to be a carrier for a disease variant not included in a report.

Next post: Red pill, or blue pill? Learn about your likely reactions to certain drugs and medications with 23andMe’s Drug Response reports – When One Size Doesn’t Fit All.

For a refresher course on genetics or help navigating the service, visit Genetics 101 on our website, or see our Frequently Asked Questions.

Check out our companion series, Ancestry at 23andMe, and other articles in 23andMe How-To.

* Based on current offerings. Note that a few of the diseases included in the Carrier Status category are not strictly recessive (Alpha-1 Antitrypsin Deficiency, Familial Hypercholesterolemia Type B, Hypertrophic Cardiomyopathy (MYBPC3 25bp-deletion), Torsion Dystonia, and BRCA Cancer Mutations); in these cases, having one copy of a mutation may be associated with increased risk for the disease or related conditions.


  • Christian

    My understanding is that there are thousands of recessive Mendelian diseases. Why is it that 23andMe tests only for 24?

    • http://23andme.com Shwu

      Hi Christian,

      23andMe uses technology that is focused on detecting common variants, plus a custom detection panel designed by us to test for variants of interest, such as mutations linked to Mendelian diseases. There is a finite number of such variants we can include, and many possible applications, not limited to Mendelian diseases, so it is simply a matter of space and resources to evaluate the scientific literature and identify the mutations that would be best to include. We also have strict quality control procedures that require that a variant be present at a minimum frequency in the population in order for us to be able to validate that the technology is testing for the variant accurately. This necessarily excludes many of the rarer mutations, for which we would not be able to do this kind of quality control.

      With our latest version of the technology (the V3 chip), we have added a number of additional variants linked to Mendelian diseases and we should be able to report on more of these diseases as our quality control and other resources allow!

  • Allan

    As someone who suffers from Kennedy’s Disease, I would urge your research organization to add this disease to your list of 24. The information below is from kennedysdisease.org. It would be an important service to track this and to inform carriers. The indicator is excess CAG repeats (>15) on the X chromosome, so it should not be too difficult to find.

    Kennedy’s Disease is a rare and currently incurable and non-treatable X-linked recessive genetic progressive neuro-muscular disease. Both the spinal and bulbar neurons are affected causing muscle weakness and wasting (atrophy) throughout the body which is most noticeable in the extremities (legs/arms), it is especially noticeable in the face and throat, and causes speech and swallowing difficulties, major muscle cramps as well as other symptoms (please see “Symptoms” section of this Web site for more detail).

    Kennedy’s Disease is an adult-onset disease with symptoms usually appearing between the ages of 30 and 50. However, earlier and later onsets have been recorded.

    Generally males with this inherited gene develop symptoms, while females with this gene are usually just carriers. In rare cases, females have been known to exhibit symptoms as well. Life expectancy is noted to be at or almost normal.

    It is estimated that 1 in 40,000 individuals worldwide have Kennedy’s Disease. However, many go undiagnosed or misdiagnosed for years. The most frequesnt misdiagnosis is the fatal Lou Gehrig’s Disease (ALS).

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