Consumer Genetic Testing Helps People at Risk for Hard to Diagnose Condition

23andMe researchers found that direct-to-consumer DNA testing can help identify individuals who are at risk for the hard-to-diagnose genetic condition alpha-1 antitrypsin deficiency (AATD), a condition that increases the risk of lung and liver disease. 

In some cases, testing not only helped flag a risk for individuals who may not have known otherwise, it also helped instigate important conversations with their healthcare provider. 

Large Study

Published in the journal Chest, the study is the largest to date to examine both the prevalence of AATD and the behavioral impact of learning that one carries a risk variant for the genetic condition. Another striking finding from the study was that one-quarter of those diagnosed with AATD were not diagnosed until after receiving their 23andMe Alpha-1 Antitrypsin (AAT) Deficiency Genetic Health Risk report.*

“This suggests that testing is helping to identify people who might otherwise slip through the cracks,” said James Ashenhurst, Ph.D., a senior scientist on 23andMe’s Health research and development team.

Hard to Diagnose

Getting treatment early can mitigate medical complications but many individuals with the condition are unaware they have it.

“Alpha-1 (AATD) is notoriously difficult to diagnose with the gap between the first symptoms and diagnosis estimated to be up to 10 years typically,” said Ashenhurst, who was also a lead author on the paper.

While it is an inherited condition, people often are unaware of family history for AATD, and that may be why they were not screened for it before learning they carried the genetic variant, according to the study.

Alerting People to their Risk

Independent of this study, 23andMe researchers went back and conducted qualitative research with some of the participants to get a richer understanding of the impact of the report. Participants in the study were anonymous to protect their privacy but many echoed the sentiment that but for the report they wouldn’t have known of their risk.

“(N)ormally people don’t find out that they have this … until they have really serious emphysema,” said one of the study participants. “[My pulmonologist] said, probably if I had not done [23andMe], 10 years down the road, he would have been seeing me with some really disabling disease… I’m really grateful that I found out about it, and that I can do something about it.”

Many of Those with AATD Don’t Know It

It’s believed that AATD affects an estimated 120,000 Americans. Unfortunately, only about six percent of those with AATD are correctly diagnosed because the symptoms resemble chronic obstructive pulmonary disease (COPD), or emphysema, and it often takes years. 

Two genetic variants in the SERPINA1 gene — called PI*Z and PI*S — lead to more than 95 percent of all cases of AATD. Those variants can decrease the transport of protein alpha-1 antitrypsin enzyme from the liver to the lungs. The protein is sent through the blood to the lungs to help protect lung tissue. Low levels in the lungs can lead to damage. In contrast, abnormal levels of alpha-1 antitrypsin in the liver can cause damage to the liver. Symptoms may include shortness of breath, wheezing, or infections in the lungs or liver. Other symptoms might include yellow skin, fatigue, rapid heartbeat, vision problems, or weight loss. 

Fortunately, there are treatments and therapies for AATD, but an early diagnosis can make a massive difference in the outcome.

Another participant in the unpublished qualitative research study told our researchers that even though she regularly experienced many of the symptoms for AATD, it wasn’t until she saw her 23andMe report and talked to her doctor about it that she was diagnosed. 

“Every time I got a cold, it would go straight to pneumonia,” she said. “So when I did [23andMe] and [23andMe] identified a risk for [AATD] … all of a sudden a key unlocked. It was like this is what’s been going on, so I immediately booked an appointment with my doctor [and] brought it in.”

The Takeaway

The study published this week was combined with clinical follow-up over two years and included data from more than 195,000 individuals. More than 1,450 of whom were diagnosed with AATD. Because of the follow-up portion of the study, the researchers learned more about the impact the information had on those who knew of their risk through direct-to-consumer genetic testing.

Individuals with risk variants were considerably more likely to discuss the results with their health care providers and family, for instance. For some, this prompted family members to also get tested for AATD. In addition, the results also appeared to prompt individuals to make behavior changes to reduce their risk. Those with risk variants were more likely to report that they reduced smoking and alcohol consumption for instance.

“There’s a lot to take away from this study,” said Ashenhurst. “Beyond identifying people who might not have known of their risk otherwise, the study shows the impact this information has on people and their family. It appears to motivate them to take the kinds of actions you would want them to take to reduce their risk.”

23andMe Health and Ancestry Service customers can see their Alpha-1 Antitrypsin (AAT) Deficiency Genetic Health Risk report here.

Not yet a customer? You can find out more about AATD here, or go here to learn more about 23andMe.

Read Claudia’s AATD story here.


*The 23andMe PGS 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. 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. 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.  The Alpha-1 Antitrypsin (AAT) Deficiency genetic health risk report is indicated for reporting of the PI*Z and PI*S variants in the SERPINA1 gene and describes if a person has variants associated with AAT deficiency and a higher risk for lung and liver disease. The variants included in this report are most common and best studied in people of European descent.