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Nevada Project Expands Enrollment, Research Into Genetic Health Risks


NEW YORK (GenomeWeb) – Renown Health and the Desert Research Institute this week opened up enrollment into the second phase of the Healthy Nevada Project, in which they hope to sequence the exomes of 40,000 participants in partnership with consumer genomics firm Helix.

Researchers plan to delve into this data and study the genetic underpinnings of cancer, heart disease, and respiratory illness.

Renown Health, a healthcare network that serves Nevada, Lake Tahoe, and northern California, and the Desert Research Institute, a firm studying environmental changes, launched the Healthy Nevada Project in 2016 to study health determinants of the local population in northern Nevada. Renown and DRI also established Renown Institute for Health Innovation, which is building a large repository of the clinical, genetic, environmental, and socioeconomic data collected from study participants.

During the project's initial phase, within 48-hours, Renown and DRI enrolled 10,000 participants who submitted their DNA sample for genotyping by consumer genomics firm 23andMe. Renown and DRI announced in January that they planned to enroll another 40,000 participants in the project and sequence their exomes through Helix.

"As we expand the Healthy Nevada Project, we're going to use more data to help our patients live healthier lives," Anthony Slonim, CEO of Renown Health, said at a webcast event this week. "As we meet the Governor's challenge to improve our health rankings … we're advancing scientific studies to help us better understand why right here in Washaw County our age-adjusted death rates for heart disease, cancer, and lower respiratory disease are one third higher than they are nationwide."

"We have work to do," Nevada Governor Brian Sandoval, who was the first person to join the study in the pilot phase, said at the event, convened to discuss how the project was growing. "When it comes to the [health] rankings, we don’t do well."

Nevada in 2016 ranked 35th in state health rankings and 45th in terms of per capita spending on healthcare, at $5,735. However, Sandoval said that the Healthy Nevada Project has put the state on the healthcare map and will help the region move up in these rankings.

In the upcoming second phase, there will be a concerted effort to enroll participants representing regional demographics. In the first part of the study, because enrollment was open to anyone 18 years or older, certain groups were over- and underrepresented.

For example, more individuals in the 31- to 70-year-old bracket joined the study than those older than 70. Also, Northern Nevadans from 135 zip codes enrolled, but only around 1,000 participants were from rural communities. Women comprised 66 percent of the enrollees. Nearly 89 percent in the pilot phase were white and only 3 percent were Hispanic, even though census estimates show that 87 percent are white and 22 percent Hispanic in Northern Nevada.

To ensure the project is considering health risks across the population in the region, in the next phase, only 10,000 slots will be open to all-comers, and the remaining ones will be filled on the basis of age, gender, ethnicity, and residence in a rural or urban locale.

The pilot phase showed that Northern Nevadans were very eager to join the project and particularly interested in learning about their genetics. "Nevadans are thirsting for a larger health conversation," said Joe Grzymski, principal investigator of the Healthy Nevada Project. He believes that the consumer genomics test results that participants receive for joining the study open a window into their health risks and motivate them to take further action to manage those risks with their doctors.

Data collected during the pilot phase from study participants showed that many Northern Nevadans had parents with cancer and heart disease, who died at a higher rate than the age-

adjusted national average. Study participants said they did not exercise as frequently as the American Heart Association recommends and wanted help changing their lifestyle using diet and weight loss tools.

In phase two, study participants will get National Geographic’s ancestry app from Helix for free. If they complete a follow-up survey, they can pick another free app related to health and wellness.

In its commercial service, Helix collects customers' samples once and performs exome sequencing, after which they can order apps from Helix's online store that interpret the data and offer insights about health, fitness, nutrition, family, and ancestry, as well as for recreational purposes. The company recently announced that with an expected $200 million in funding from investors, it would introduce many new apps in its online marketplace, particularly apps that provide customers health-related insights.

Slonim noted that some people joining the study will have serious health issues, while others are relatively healthy. On one end of the spectrum, a participant might just want a report on their genetic ancestry, he acknowledged, and on the other end, there will be those who want to really get into the genetic details. "And wherever you might be on the continuum, our job is to inform you and to help you make better decisions," Slonim said.

In this next phase, experts will also start a number of clinical programs and research studies on heart disease, cancer, and lower respiratory disease. Age-related death rates among Northern Nevadans are 33 percent above the national rate for these three conditions.

Christopher Rowan, a cardiologist at Renown Health, referenced research by the Broad Institute's Sekar Kathiresan and colleagues, who have developed a polygenic risk score for coronary artery disease. They showed in a study published in 2016 in the New England Journal of Medicine that individuals at high genetic risk for CAD who had a favorable lifestyle had a 50 percent lower risk for CAD than those with an unfavorable lifestyle.

"We’ve recently started a project where we took data from the original 10,000 people … and created a risk model looking at the genetic risk of those people, and we started recruiting them to get them in and see us as quickly as possible, to see if they’re at truly higher risk for having a heart attack," Rowan said. The Renown Institute for Health Innovation will also provide advanced calcium score screenings to pilot phase participants at higher risk for cardiovascular disease in order to study the genetic underpinnings of calcium build up in the heart.

Pilot phase data also showed that "bad air events," such as wildfires, correlated with increased regional healthcare utilization. As such, the Renown Institute for Health Innovation will study whether there are genetic markers that increase people’s susceptibility to respiratory ailments.

Christos Galanopoulos, chief clinical officer at the Renown Institute for Cancer, highlighted the work of Mavaddat et al, published in 2015 in the Journal of the National Cancer Institute, where the researchers investigated a 77 SNP score for assessing risk for breast cancer, and concluded that it stratified risk in women with and without a family history of the disease.The partnership with Helix will enable experts at Renown to delve into the genetic risk for breast and other cancers, Galanopoulos said.

The researchers will garner a hundred times more genetic data by moving form SNP genotyping to exome sequencing. "The idea is to engage in a conversation with people regarding genetic risk and metabolic markers, and track people longitudinally to see if the predictions match the data," Grzymski told GenomeWeb.

Sequencing will also reveal whether participants have mutations in clinically relevant genes, such as BRCA1 and BRCA2, associated with increased risks for breast, ovarian, and prostate cancers.

In the current expansion phase of the study, researchers have been testing its infrastructure for recruiting and consenting new participants, and so far, around 1,000 people have joined the project. More than 90 percent of them have consented to partake in future research and have said they want to be contacted by Renown if genetic testing identifies a health risk factor that experts feel is important to relay to the patient.

Grzymski said that the project leaders are still figuring out what they should report back in this regard and how they will notify participants ー whether through an intermediary app delivering a report and a call from the doctor or through Renown’s clinical team.