NEW YORK (GenomeWeb) – The Renown Institute for Health Innovation this week began returning genetic test results for familial hypercholesterolemia to participants in its Healthy Nevada Project, and in the coming months will report results for hereditary breast and ovarian cancer and Lynch syndrome.
Healthcare network Renown Health and environmental studies organization Desert Research Institute established the Renown Institute and launched the Healthy Nevada Project in 2016 to investigate the health determinants of the residents of northern Nevada. The local population in this region has an age-adjusted death rate from heart disease, cancer, and chronic lower respiratory disease that is 33 percent higher than the national average.
Within the Healthy Nevada Project, researchers are collecting clinical, environmental, socioeconomic, and genetic data in a repository managed by the Renown Institute and studying the multifactorial causes of disease. Renown and DRI are working with San Francisco Bay Area-based Helix to sequence the exomes of participants and collect their genetic data. This week, six months after Helix began sequencing Healthy Nevada participants, the project coordinators have begun to report back actionable, incidental findings to those who said they wanted to know this information.
The Healthy Nevada Project has been able to enroll participants far quicker than population health studies are typically able by riding the wave of consumer interest in learning about their genes. In its initial phase, Renown and DRI had planned to enroll 10,000 participants and reached their goal within 48 hours. A big draw for participants, according to the leaders of the project, was that they could get free genetic test reports from Mountain View, California-based consumer genomics firm 23andMe and learn about their ancestry, traits, wellness, and carrier status.
Following this experience, Renown and DRI earlier this year announced their aim to enroll 40,000 participants within the project. This time, they partnered with Helix, which operates an online marketplace of apps for consumers interested in learning what their genes say about their ancestry, and how they influence their diet, endurance, risks for diseases, and ability to metabolize drugs. In return for volunteering to partake in research, participants get National Geographic's ancestry app for free.
People rarely get anything back for participating in research, but providing people a chance to explore their own DNA information through Helix is motivating people to join the study and stay engaged, according to Anthony Slonim, CEO of Renown Health. Since March, when Renown and DRI began the expanded enrollment push, between 35,000 and 36,000 participants have had their exomes tested.
Within the initial 10,000 enrollees in the pilot phase, the response rate to health surveys was greater than 50 percent. In the expanded phase, participants are also asked to complete a survey to gather information on their health and lifestyle factors, which more than 50 percent of enrollees are completing.
After participants complete health surveys, they get another free app within Helix's platform. They can choose from nutrition and fitness apps from Lose It!, Intelliseq, and DNAFit; apps to learn about traits and ancestry by HumanCode and Insitome; or Sema4's carrier screening app.
Helix's participation in the Healthy Nevada Project also opens up another channel for the company to gain new customers. Project participants, once introduced to Helix's apps marketplace through the study, may decide to buy additional products on the website. However, Justin Kao, Helix cofounder and senior vice president, declined to disclose the extent to which this research partnership has bolstered the firm's customer base.
Renown's goal in offering participants free genomics apps through Helix is to not just engage them in the project, but also in their healthcare. "We don't want the health part of healthcare to be forgotten," said Joseph Grzymski, principal investigator of the Healthy Nevada Project and chief scientific officer of Renown Health. "We're engaging in this massive effort to instigate some behavior change."
This is why the project's leaders decided to return actionable, incidental findings following exome sequencing to participants who indicated they wanted to know this information during the consent process. Starting this week, participants will learn if they harbor likely pathogenic or pathogenic genetic variants associated with FH, an inherited condition that hinders the body's ability to recycle low density lipoprotein (LDL) from the blood.
"We're going through the process of identifying who is at risk," Slonim said. Clinical coordinators involved with the project will reach out to participants who want to know their results, after which they can see a doctor and speak with a genetic counselor.
FH occurs in around 1 out of 220 people and the FH Foundation estimates that there are 30 million people with the condition worldwide, though more than 90 percent of people with the condition around the world and more than 1 million in the US are undiagnosed. An expert panel convened by the FH Foundation recommended earlier this year that individuals with very high LDL cholesterol and a positive family history of high cholesterol or early heart attack should be evaluated for pathogenic variants in at least three genes: LDLR, APOB, and PCSK9.
Renown Institute has also begun advanced calcium score screenings for project participants who are at high risk for cardiovascular disease, so researchers can study the associations between genetics and calcium accumulation in the heart.
More than 2,000 unique genetic variants associated with FH have been identified to date, with around half being classified as pathogenic or likely pathogenic. More than 90 percent of pathogenic variants are in LDLR, between 5 percent and 10 percent are in APOB, and less than 1 percent are in PCSK9. Because genetic testing doesn't always detect a pathogenic variant in one of these genes, experts say that FH should be diagnosed clinically in the event of a negative test result.
Because the genetic information being reported back has implications for participants and their family's health, Renown has created literature they can take to their primary care providers and their relatives, who might also be at risk and benefit from testing. Relatives of study participants who want to get tested can do so for free by joining the Healthy Nevada Project if they live in Northern Nevada, while those living outside the area will receive information they can take to their doctors.
For those that don't have pathogenic or likely pathogenic mutations in the tested genes, the project will explain that researchers haven't identified all disease-associated variants and that they still might be at risk for those conditions based on lifestyle, diet, and environmental factors. It is also important that participants understand that variant classifications may change over time with mounting evidence, according to Grzymski. He said there is a process in place for iterative reanalysis of variants, and clinically meaningful changes in variant classifications will be communicated to participants.
In coming months, consented project participants will also find out if they have mutations in BRCA1 and BRCA2 genes associated with hereditary breast and ovarian cancer syndrome, as well as mutations in MLH1, MSH2, MSH6, and PMS2 associated with Lynch syndrome. The Centers for Disease Control and Prevention has determined these three conditions — FH, hereditary breast and ovarian cancer syndrome, and Lynch syndrome — to be poorly managed, but notes that screening for mutations in genes associated with these diseases could improve the population's health through early detection and prevention.
Other groups who have launched broad genetic screening efforts for these conditions have found that the prevalence of risk mutations are higher in the population than previous estimates. For example, based on exome sequencing data from more than 50,000 participants in the MyCode Community Health Initiative, Geisinger Health System in Pennsylvania found 267 people with likely pathogenic or pathogenic BRCA1/2 variants. Researchers involved in the study concluded that the prevalence of BRCA1/2 mutations among patients within Geisinger's healthcare system may be significantly higher than was previously estimated and that the prevalence of mutations for FH and Lynch syndrome may be similarly underestimated.
"We anticipate that our frequencies are going to be similar to generalized large studies, the Geisinger study being the best one," Grzymski said, adding that Renown will publish the prevalence of these disease-linked markers within its own population.
Renown and DRI said in a statement that they expect to meet the 40,000-person enrollment goal for the Healthy Nevada Project by year end. Including the 10,000 participants involved in the pilot phase, the project has enrolled around 10 percent of the population in Northern Nevada. For the second phase of the study, the project leaders are aiming to enroll and genomically profile more than 250,000 participants throughout Nevada, and eventually expand the scope of the project to other communities around the US.