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New Consumer Genomics Offerings for Alzheimer's Risk Come to Market Despite Provider Reluctance


NEW YORK (GenomeWeb) – Mainstream doctors may not like it, but as of last week people interested in learning their genetic risk for late-onset Alzheimer's can purchase two new tests online without waiting for their own physicians to order them.

One is an APOE test from ADx Healthcare sold through the Helix online genomics marketplace. The other offering is a polygenic hazard score, developed by health technology startup HealthLytix and marketed by a firm called Dash Genomics, which gauges one's risk for developing late-onset Alzheimer's by factoring in the person's age and genetic information.

ADx Healthcare is a subsidiary of Northwest Pathology in Bellingham, Washington, which offers a suite of molecular, anatomical, and surgical pathology services, as well as APOE testing that doctors can order. Recognizing that a lot of doctors are unwilling to order APOE testing, the company entered the consumer genomics space to enable access for people who still want to learn this information.

The consumer genomics industry has been a disruptive force for the traditional medical establishment. After purchasing genetic tests online to learn their risks for incurable and unpreventable diseases like Alzheimer's, the customers of these consumer genomics firms increasingly end up in the doctors' office asking how to make sense of information in reports based on emerging science and not ready for clinical implementation. 

These consumer genomics companies, in turn, have accused healthcare providers of paternalism and of failing to recognize that their patients want to know this information because it has personal value to them. "Emerging research can take a while to be accepted by mainstream healthcare providers," ADx Healthcare states on the purchase page for the APOE test, in reference to studies suggesting that early lifestyle changes may lower the risk of developing Alzheimer's. "You aren’t limited by what your doctor's office offers or what your insurance will cover."

"In a perfect world, having all doctors understand the value of genetic testing and ordering it as appropriate would be the best thing to do, but that doesn't happen in reality," said Ryan Fortna, founder of ADx Healthcare, which charges $160 for its APOE test (plus $40 for exome sequencing through Helix). "The best way for patients to get this information is for them to be informed about what's available and initiate the interest in it."

The company reports customers' APOE results, provides a lifetime risk assessment based on their APOE genotype, age, and gender, and discusses the latest research on lifestyle changes associated with lowering the risk of dementia and improving brain health, such as getting sufficient sleep and exercise, lowering stress, lowering blood glucose and insulin levels.

ADx Healthcare is starting off with the APOE test offering on Helix but is planning to launch a polygenic Alzheimer's risk score in the coming months.

Dash Genomics' business model for its so-called polygenic hazard score relies on customers already having been genotyped by 23andMe and, two of the top consumer genomics companies. The polygenic hazard score, developed by HealthLytix and available currently for $99 (discounted from $149), analyzes customers' genotyping data and combines this with population-based incidence rates to calculate their risk for Alzheimer's-related cognitive decline as a function of their age.

In PLOS Medicine last year, researchers from the University of California, San Diego and UC San Francisco described the development and validation of the polygenic hazard score based on 33 loci near 28 genes, and concluded that the score can predict age-specific risk of Alzheimer's beyond APOE. HealthLytix then expanded this algorithm based on 600,000 loci across the genome typically found in 23andMe and raw data reports. 

"After publishing the proof-of-concept study last year, a lot of people asked when this score would be available," said Chun Fan, chief data scientist at HealthLytix, who played a leading role in developing the polygenic hazard score. Instead of setting up a wet lab to do the genotyping, Fan recognized that millions of people already had this data through 23andMe and HealthLytix partnered with Dash Genomics to make use of this data and quickly make the polygenic hazard score available on the market.

HealthLytix is also in early discussions with Helix to market its polygenic hazard score via its online genomics marketplace.

Supporting customers

On Dash Genomics' website there are numerous warnings and caveats about the polygenic hazard score. The company tells customers that the analysis doesn't meet the standards required for medical use, that the raw data from 23andMe and may contain errors, which may affect the accuracy of risk predictions, and that risk estimates are largely based on people of Caucasian ancestry and may not be relevant to other ethnic groups.

Regulators have expressed concern that consumers may not understand the limitations of the genetic tests they've purchased online or consent to testing without considering the psychological impact the information could have on them.

23andMe, as part of its efforts to garner FDA marketing authorization for its health risk tests, including APOE testing, had to show that consumers comprehended the information in its education modules and test reports. All the same, during the FDA review process, there was a lot of discussion about the risks of offering APOE testing directly to consumers, according to Alberto Gutierrez, former director of the agency's Office of In Vitro Diagnostics and Radiological Health.

"The agency worried whether people will be able to handle that and there is some evidence that [such risk information] may be difficult for some people to deal with," said Gutierrez. While the FDA authorized 23andMe's health risk reports for direct-to-consumer sales last year, without requiring that the company offer genetic counseling as part of the service, he personally believes 23andMe should provide this support. 

In the general population, between 10 percent and 15 percent of people will get late-onset Alzheimer's by age 85. But those with a version of the APOE gene, APOE4, have a much greater chance of getting the disease and at younger age. Having one copy of the APOE4 allele can increase one's lifetime risk for the disease by three times compared to the general population, and having two copies increases the risk twelvefold.

But numerous professional society guidelines recommend against APOE testing, noting that APOE4 carriers aren't destined to get Alzheimer's, risk estimates can vary based on one's ethnicity, and there aren't proven preventive measures. The 2011 joint guidelines from the American College of Medical Genetics and the National Society of Genetic Counselors advises against direct-to-consumer (DTC) testing of APOE variants and recommends that APOE testing should only occur in the context of genetic counseling. 

Earlier this year, Doris Zallen, professor of science and technology studies at Virginia Tech and a faculty member in the school of medicine, published a study where between 2015 and 2017 she interviewed people who had gotten APOE testing through consumer genomics services without genetic counseling and found a significant number of them experienced psychological distress once they learned they were at high risk. Over time, some of these individuals felt better about their results, as they started to eat healthier, exercise, or take supplements, but a few of the study participants remained depressed.  

The newer entrants to the consumer genomics space, ADx Healthcare and Dash Genomics, are addressing these concerns differently at the moment, though both companies recognize the importance of helping customers understand their results.

All health-related genetic tests sold on the Helix website require authorization from a doctor employed by PWN Health, which operates a national physician network. The same organization also provides genetic counseling for the price of the APOE test. "Our option allows [consumers] to initiate the testing by showing their interest in it but still have a physician involved to make sure testing is appropriate for them," Fortna said.

When ordering the test, customers fill out a health history questionnaire, which tries to ascertain if the customer has a family history of Alzheimer's or dementia or a history of mental illness. After reviewing the answers, it's up to PWN Health's doctors to decide whether to approve an order, and they may not, said Marci Hardy, director of health sciences at ADx Healthcare, if the customer indicates he or she has been diagnosed with depression, for example.

When the results are ready for viewing, customers can decide to open the report on their own or go through it with a genetic counselor on the phone. In an effort to mitigate concerns about conflicts of interest with this model, Helix discloses on the test ordering page the portion of the test price that goes to PWN Health for physician approval and genetic counseling services. Moreover, providers and counselors are paid for each test order they review and counseling session, not for orders they approve.

Dash Genomics' service doesn't currently involve providers in the ordering process or include genetic counseling, but on its website it tells customers to consult a medical professional and directs them to the National Society of Genetic Counselors' 'Find a genetic counselor' service.

HealthLytix is working with Dash Genomics to figure out the best way to provide active genetic counseling for individuals that the polygenic hazard score identifies as high risk, and the companies are currently in discussions with a genetic counseling partner. Additionally, if HealthLytix decides to sell its polygenic score through Helix, it will be physician ordered and include genetic counseling, as is required for all health-related tests available through that site.

Need for new educational tools

Helix and ADx Healthcare are taking a step in the right direction, Zallen said, by offering genetic counseling as part of its service. Her research shows that consumer genomics companies need to do a better job communicating the potential impact testing can have on them before they submit to testing and provide genetic counseling to help people understand potentially life-altering results that are all too easily accessed through mobile devices.

One of the women Zallen interviewed for her study on the psychological impact of direct-to-consumer APOE testing, received an email while she was at a dinner party notifying her that results were ready for viewing. As she started clicking through it on her phone, some things she learned were fun, some weren't interesting, but then she came to the Alzheimer's report and decided in the moment to view it. She was at high risk.

"For the rest of the dinner party she said she was numb and everybody wondered what was wrong with her," Zallen recounted. "You don't know what the circumstances are in which people are receiving this information. It may not be the studious library environment."

The 26 interviewees in Zallen's study got initial testing through 23andMe, though some learned their APOE status by having their raw genotyping data analyzed through a company called Promethease, and one individual consulted SNPedia, a website containing information on genetic variants. Eleven people learned they carried one copy of the APOE4 allele and 15 found out they had two copies. None had pre-test genetic counseling.

In interviews with Zallen, five of the 11 people carrying a single APOE4 copy and 10 out of the 15 individuals carrying two copies said they were shocked to find out they were at high risk for Alzheimer's and went through a psychologically painful, sometimes incapacitating, period.

23andMe and Promethease offer online educational resources and information about how to connect to genetic counselors but don't offer pre- or post-test genetic counseling as part of their services. After learning their results, these individuals had to figure out complex medical literature and seek out support for themselves, such as, an online support group initially started within the 23andMe customer community.

When some of these individuals took their test results to their doctors, healthcare providers reinforced dire prognoses 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.

"The people I talked to were unprepared," Zallen said. "They got this dump of genetic information, and then they were abandoned."

Over the long term, 23 out of the 26 individuals came to feel better about knowing their APOE status. They ultimately felt this knowledge benefitted them because they could eat better, exercise more, take supplements, and pay more attention to cardiovascular and diabetes risk factors. "Nobody knows if those [actions] are going to work" in terms of staving off Alzheimer's, Zallen said. "And while these people felt this was useful, they still regretted the suffering and the rejection by the medical community."

Importantly, three people she interviewed weren't empowered by the potential for lifestyle changes to make a positive difference. "Those three people felt that this knowledge was the dark cloud that ruins every day of their lives," Zallen said. "Even having [the wellness information] didn't make them feel better."

Personal utility

Ultimately, companies like ADx Healthcare and Dash Genomics want their customers to feel better — or have a sense of empowerment — from knowing their genetic information than remaining in the dark about it. There may not be proven ways to prevent Alzheimer's, but people may use this information to guide other life decisions.

"Maybe they're not going to work 80 hours a week anymore, or make better financial decisions," said Elissa Levin, director of policy and clinical affairs at Helix. "These are real considerations that are of value to people … and that's something that doesn't get enough attention, especially among the clinical professional audience."  

Although Dash Genomics tells customers that they shouldn't use the Alzheimer's onset risk estimates to make medical decisions, people interested in personal genomics may still want to know their polygenic hazard score, according to Fan. "We hope to help people understand how the latest research in the field applies to them," which in turn "can help people better understand themselves and inform their lives," he said.

Spearheaded by Rahul Desikan at UC San Francisco, Fan's team and collaborators have published papers showing the association of this algorithm with Alzheimer's biomarkers, such as amyloid and tau depositions, and its utility when combined with brain imaging data and cognitive measures. As such, individuals who find out they're at high risk of Alzheimer's onset in the next year or over the next five years based on the score can take this information to their doctors, who, based on this information, may decide to conduct additional diagnostic screening. 

ADx Healthcare's Fortna pointed to emerging research suggesting that early lifestyle changes are associated with lower lifetime risk of Alzheimer's. Last year, the Lancet Commission reviewed the available evidence and reported that one-third of dementias worldwide can be prevented if, for example, people stop smoking or lowered their propensity for hypertension and obesity.  

"We're not talking about giving someone a chemotherapy drug that's going to give them terrible side effects," Fortna said. "Almost all the things we're talking about are things that also have beneficial effects on health and other disease preventive measures anyway. We feel fairly comfortable we're not doing any harm."

Zallen pointed out that Helix discusses the value of learning one's APOE status on the purchase page for the test, but she feels the company doesn't do a good job of highlighting the reasons someone may not want to know. "Of course, they are selling a product," she noted. "But there are reasons for not getting tested, and these came up in the interviews I did." The psychological adverse reactions reported in her study occurred among those who had specifically sought out APOE testing, those who had learned results unexpectedly, those with a family history with Alzheimer's, and those without.

Zallen and a research team developed and published a free, web-based decision aid ( to help people think through whether they truly want to learn their APOE status. The online decision aid asks users to critically consider their family history of Alzheimer's, whether the test will give useful information, if is this the right time for testing, and if the advantages of obtaining this information are greater than the disadvantages. To date, more than 1,200 people have used the tool and the vast majority found it helpful, with 35 percent indicating they'd be more likely to get tested, and 20 percent saying they were less inclined to learn their APOE status. 

As people's interest in genetic testing grows, increasing the need for genetic counseling and education, Zallen believes that the consumer genomics industry has an obligation to supplement the decision process with these kinds of tools. "We have to recognize these are complex decisions that impact people, and not all tests are right for everyone," Zallen said. "You can't just supply [this] information to people and think that's enough."