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Ancestry Begins Genetic Testing Services for Health

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This article has been updated to note that there are close to 5,000 BRCA1/2 variants known to increase risk for breast and ovarian cancer. Additionally, based on information from Ancestry after the article's publication, the story now specifies that the NGS service when launched will conduct exome sequencing.

NEW YORK – Recreational genealogy firm Ancestry has partnered with Illumina and Quest Diagnostics to expand into health-related genetic testing. 

The company today announced two services: AncestryHealth Core, which is available immediately and uses microarray genotyping performed by Illumina, and AncestryHealth Plus, a membership-based offering that will be available for customers in a few months using next-generation sequencing conducted by Quest Diagnostics. Physicians in telemedicine firm PWNHealth's network will review and approve customer orders based on online questionnaires , at which point patient saliva samples will be sent to the labs for analysis and reporting. 

Ancestry operates the AncestryDNA genealogy testing service, which boasts more than 15 million customers who have been tested on a microarray platform. "We wanted to offer this core base something that is actionable and meaningful now," said Sarah South, VP of laboratory sciences at Ancestry. "Looking at what we could do with our current technology allowed us to offer something to them now at scale. We do recognize the limitations of [genotyping] for some conditions and that's why we added the next-generation sequencing offering for those interested in more comprehensive information over a period of time." 

The Core service costs $49 for existing customers of genealogy testing and $149 for new customers, which includes access to AncestryDNA. The Plus service is $199 for new customers, with a $49 biannual membership fee that kicks in after the first six months. Existing AncestryDNA customers can upgrade to Plus for $49, and will pay another $49 once NGS results are available, in addition to the membership fee every six months. 

At launch, Ancestry's existing and new customers, regardless of whether they opt for the Core or Plus service, will receive results based on genotyping. Customers using Plus will be in a queue for NGS-based expanded analysis, and with an annual membership can receive updated results based on ongoing research and reports on new health conditions when they are launched. 

As more customers purchase the Core service, there will be those who also express interest in the Plus service, allowing Ancestry to gauge demand. The company expects to upgrade interested customers to the NGS-based service in early 2020. AncestryHealth Plus will conduct exome sequencing and initially report findings in the same genes as genotyped in AncestryHealth Core, plus PCSK9 for familial hypercholesterolemia.

Within these services, Ancestry will report variants that are "clearly understood as associated with a condition," South said, since expert guidelines advise against taking action based on variants of unknown significance. Unlike genotyping, which detects specific variants, NGS provides a window into novel variants that have unclear links to disease, and Quest's lab will monitor the evidence around clinical significance for these variants and report them to Plus members if a variant's status changes from uncertain to pathogenic. 

The services will gauge mutations in genes associated with risk for hereditary breast and ovarian cancer (BRCA1 and BRCA2); Lynch syndrome (MLH1, MSH2, MSH6, and PMS2), familial hypercholesterolemia, hypertrophic/dilated cardiomyopathy (MYH7 and MYBPC3), hereditary hemochromatosis, and thrombosis. They will also offer carrier screening for diseases such as cystic fibrosis, Tay-Sachs, and sickle cell. 

According to the US Centers for Disease Control and Prevention, there are almost 2 million people in the US with genetic markers that place them at increased risk for hereditary breast and ovarian cancer risk, Lynch syndrome, and familial hypercholesterolemia, but many are unaware because the health system doesn't adequately screen for these conditions. 

"We wanted to focus on things that have actionability, that if an individual understands that they are at increased risk for this condition, there are meaningful conversations they can have with their physician, there are professional guidelines on actions they can take before they develop clinical symptoms in order to mitigate the consequences of the condition," said South. 

Ancestry and its testing partners will perform these health-related tests in CLIA-certified labs, while PWNHealth will facilitate physician ordering and genetic counseling. 

This is increasingly the strategy genetic testing companies are using to enter the consumer genomics space, despite a US Food and Drug Administration crack down several years ago where the agency asked that health-related direct-to-consumer genetic tests be submitted for premarket review. 23andMe is the only consumer genetics firm to have taken this path, but doing so has brought more complications. Because FDA's regulatory authorizations come with caveats  to not use the test results to make medical decisions, and in some cases require confirmatory testing, genetic counselors and medical professionals say patients are often confused about the utility of 23andMe's tests and what it means to garner FDA authorization. 

Further complicating matters is the fact that the FDA continues to practice "enforcement discretion" over lab-developed tests, and the lab industry has been adamant that the agency lacks authority to regulate the space. Quest, one of the largest reference labs in the world, for example, is a member of the American Clinical Laboratory Association, which has been quite vocal on this point. Meanwhile, consumer genomics firms have embraced a strategy of partnering with CLIA-certified labs and using a physician network to facilitate test ordering. Even though an individual's own physician might not be doing the ordering, this allows companies to avoid the direct-to-consumer category, and fall under FDA's "enforcement discretion." 

Ancestry's approach mirrors that of Israeli online genealogy firm MyHeritage, which earlier this year transitioned into health-related genetic testing. The company's tests are not available in New York, New Jersey, and Rhode Island. 

Although a recent Ancestry survey showed 83 percent of customers were looking for new ways to improve their health, the three-decades-old genealogy company took its time entering the health genetic testing space. "We have heard from our customers for a while that they're interested in learning more about themselves through their origins, [relatives] matching, as well as through their health and their family's health," South said. "But we wanted to make sure we did this in a really supported environment and it took some time for us to make sure we understood the current health ecosystem and how we can integrate with that." 

Regulatory challenges, physician reluctance, and their lack of genomics knowhow have all made it hard for customers of genetic testing firms like 23andMe to apply the health risk information they learn to their day-to-day care. 

In one study, for example, Doris Zallen from Virginia Tech University interviewed people who got APOE testing from consumer genomics services and learned their risk for late-onset Alzheimer's disease. The survey showed that upon learning they were at heightened genetic risk, people were left to seek out information and support on their own. Some of these individuals took their test results to their doctors, but healthcare providers reinforced dire prognosis without much support. "Well, good luck with that," one individual recalled a healthcare provider saying, and another recalled being told that it's not a matter of if she'd get Alzheimer's but when. 

Doctors, in turn, have cited limitations of consumer genomics testing as the reason for not wanting to give too much importance to such test results during patient visits. For example, 23andMe reports three variants in BRCA1/2 that largely show up in the Ashkenazi Jewish population, but there are close to 5,000 variants in these genes known to increase risk for breast and ovarian cancer. Therefore, a negative genetic test report from 23andMe on just these three variants is not meaningful in the same way that a negative NGS test analyzing these two genes would be. 

South said Ancestry worked with behavioral scientists to fine tune how it reports results to customers, focusing on presenting information in a way that's easily understandable and to encourage them to take the next step in their care if necessary. For example, in customer reports Ancestry has incorporated a "key takeaways" box to highlight and summarize the findings. "If there was not a [pathogenic] variant found, we don't say you're negative, but just that no variant was found," she said. 

Both the Core and Plus products include a family health history tool allowing customers to record information about diseases that they or their relatives have had. Ancestry encourages customers to use the tool and fill out this information so it can be incorporated into reports that tell patients they may still be at heightened risk based on family history even if a pathogenic variant was not found. 

Prior to testing, Ancestry will provide educational tools to help patients understand its limitations and what they can hope to learn, while post-test education will focus on explaining what the results mean in the context of their health and family history. For the cost of the services, PWNHealth will provide pre-test genetic counseling, if ordering doctors determine it is necessary but mostly at customers' request, as well as post-test counseling. Genetic counselors will be available to customers through webinars, online chats, and via telephone.

In evaluating the health ecosystem, Ancestry also recognized that physicians are an end user of its genetic health reports, and the importance of supporting them. The company has created a separate report for them that discusses the limitations of the tests, cites what professional society guidelines say about genetic testing for specific conditions, as well as data from peer-reviewed papers. "It comes to them in language that they understand," South said. 

As the health services mature and new reports are launched, Ancestry will remain focused on ensuring that patients and physicians feel supported and understand the information conveyed to them, South said. "That's going to have to be number one to us."