Direct-to-consumer testing may help identify alpha-1 antitrypsin deficiency

Direct-to-consumer testing, combined with clinical follow-up, helped identify patients with undiagnosed alpha-1 antitrypsin deficiency, according to data published in Chest.

This autosomal co-dominant condition predisposes individuals to emphysema, as well as cirrhosis, panniculitis and vasculitis, according to the researchers.

“Millions of people have received direct-to-consumer genomic testing that includes reports on heritable risks for medical conditions, but what people do with this information is not well understood,” James R. Ashenhurst, PhD, a senior scientist at 23andMe, told Healio. “The 23andMe report on alpha-1 antitrypsin deficiency provided an opportunity to understand if reporting genetic results associated with this rare and underdiagnosed condition to a general consumer population is one additional way to identify individuals with alpha-1 antitrypsin deficiency and potentially improve public health.”

The cross-sectional study enrolled 195,014 individuals who responded to a 23andMe survey about alpha-1 antitrypsin deficiency. Those who were diagnosed with alpha-1 antitrypsin deficiency from a physician in a clinical setting responded to follow-up questions about diagnostic history and whether the diagnosis occurred before or after viewing their direct-to-consumer report.

The allele frequency for the PI*S (15.1%) and PI*Z (6.5%) alpha-1 antitrypsin deficiency variants was 21.6%. Among all participants, 0.63% had the PI*ZZ variant, with 50% of these participants reporting having their diagnosis confirmed by a physician.

Twenty-seven percent of participants with physician-diagnosed alpha-1 antitrypsin deficiency reported becoming aware of their deficiency first through the direct-to-consumer test, with a diagnostic delay interval of 22.3 years among participants who were newly aware of their deficiency.

Direct-to-consumer test results were frequently shared with health care providers by participants, which led to a high reported impact of learning about their alpha-1 antitrypsin deficiency, the researchers wrote. Among all participants with the PI*ZZ variant, 51.1% shared their direct-to-consumer result with their health care provider.

Compared with participants without a Z allele, participants with the PI*ZZ variant reported a reduction in smoking (OR = 1.7; 95% CI, 1.4-2.2) and reduced alcohol consumption (OR = 4; 95% CI, 2.6-5.9) as a result of receiving their direct-to-consumer result.

"This study provides evidence suggesting that direct-to-consumer genomic testing aided in the identification of individuals and families at risk for the rare condition alpha-1 antitrypsin deficiency who may have otherwise been missed by the health care system. Furthermore, the information in the personalized alpha-1 antitrypsin deficiency report encouraged discussions within families and with medical professionals about heritable risks for alpha-1 antitrypsin deficiency, and the direct-to-consumer report prompted positive self-reported behavior change, especially among those with greater genetic risk,” Ashenhurst told Healio.

Ashenhurst said further research might focus on barriers to preventing greater integration of “highly actionable genetic information” into standard medical care.

“This study focused on a rare condition, but there are also genetic tests that can estimate the likelihood of developing more common conditions, like type 2 diabetes. What do people do with this information, and how could medical practice integrate these results into prevention practices?” Ashenhurst said. “Although genetics are only part of the story — lifestyle and other factors are just as important for understanding risks — future research is needed to understand how genomic information can be used to support health and prevention for common conditions in the broader population.”

For more information:

James R. Ashenhurst, PhD, can be reached at jashenhurst@23andme.com.