A large-scale genomic sequencing study by the Geisinger Health System and Regeneron is expected to sequence at least 5,000 exomes this year and to report medically actionable results back to participants starting this fall, Clinical Sequencing News has learned.
The goal of the five-year research study, which Geisinger and Regeneron announced in January, is to recruit at least 100,000 Geisinger patients and sequence their exomes or genomes in order to find new associations between genes and disease.
Regeneron, based in Tarrytown, NY, will generate the sequence data – initially from exomes – in its newly-established Regeneron Genetics Center and will use the results, in conjunction with certain de-identified phenotypic and clinical data, in its target discovery and drug development programs. "We think [this project] will have enormous long-term value in helping us understand the genetic causes and factors in a variety of major diseases," a company spokesperson told CSN.
Geisinger Health System, which is based in Danville, Pa., and provides healthcare to more than 2.6 million individuals, hopes the results will allow its doctors to diagnose diseases earlier or prevent their onset. "We expect that many of our patients will directly benefit from their participation in this research because of Geisinger's ability to validate and return clinically actionable results to them, and all of our patients will benefit from the knowledge we gain in how to help set the standard for genomically informed care," said David Ledbetter, executive VP and CSO of the Geisinger Health System, at the time of the announcement.
The study came about after Regeneron approached Geisinger about a possible partnership more than a year ago. After a long period of negotiations and due diligence, "both organizations felt that it was a good match," Michael Murray, director of clinical genomics at Geisinger's Genomic Medicine Institute, told CSN. "Both are recognized for being innovative thinkers within their own area, and we agreed that we could do this project, we could protect the interests of our patients in the meantime, and that both groups would benefit."
For Geisinger, he said, obtaining genome data from 100,000 patients "seemed like a great opportunity" that might not otherwise be possible on this scale. While the parties did not disclose financial details about their collaboration, Murray did confirm that Regeneron will cover the cost of sequencing.
Patient samples will come from the MyCode biorepository, which Geisinger started in 2006 in order to support research studies. As of the end of 2013, the MyCode cohort, for which Geisinger recruits when patients visit their doctors, had grown to almost 50,000 members.
While their original consent did allow for their genomes to be sequenced, and for them to be recontacted if research findings needed to be delivered back to them, the Geisinger researchers felt that a new consent was needed to cover the "return of results" project they were planning for the Geisinger-Regeneron genomic sequencing study.
As a result, they started a reconsenting effort last October and are planning to recruit 20,000 additional members under the new consent this year, and 100,000 within five years. As part of the new consent, patients agreed to the return of medically actionable genomic results, though not every participant can expect to receive such results. Eventually, patients will be able to sign up for the biorepository, which has been renamed the Geisinger MyCode Community Health Initiative, electronically.
Murray said Geisinger is aware of patients' privacy and other concerns regarding genome sequencing and has had "an ongoing conversation" with both participants and its patient community at large about these. It has "systems set up that we think are best in class that protect patient information from going outside our firewalls," and while Regeneron will have access to "some of the phenotypic information," it will not have access to personal health records.
Under the Geisinger-Regeneron project, the plan is to sequence the exomes of at least 5,000 MyCode individuals this year, according to Murray, though the exact timeline has not been determined yet. Geisinger hopes to obtain the first sequencing results this summer, and to return results to the first patients around the fall.
In general, the study will sequence any MyCode patient because "there is a benefit to having a large, relatively unselected group of patients," Murray said. But the project may also start recruiting patient groups of particular interest to Geisinger or Regeneron. "We will be moving ahead in both areas," he said.
Both parties will have access to the sequence data, though it has not yet been determined how. "Whether it would be a cloud-based solution or some other solution is being discussed by many experts on both sides," Murray said.
Also, Regeneron's sequencing facility is not CLIA-certified, and any actionable results will be confirmed by a clinical laboratory before being returned to patients and doctors in the form of a "clinical lab report that looks much like a standard clinical lab report and can go right into the electronic medical record," Murray said. Geisinger is currently negotiating with "top reference laboratories" to provide confirmatory sequencing services and create the reports, he added, "and then at some point we may bring it in house."
The list of genes for which the study will provide results has not been finalized, but it will "likely include all or most of" the 65 genes specified in the recommendations by the American College of Medical Genetics and Genomics for reporting incidental findings last year, Murray said.
He expects the list to include the BRCA1 and 2 genes, to which Myriad Genetics claims certain intellectual property rights, even after the US Supreme Court invalidated some of its claims last year.
In addition to the ACMG-recommended genes and variants, the project plans to report – either initially, or at a later stage – pharmacogenomic variants and carrier status information for autosomal recessive disorders.
As part of the Electronic Medical Records and Genomics (eMERGE) consortium, Geisinger is already working on delivering pharmacogenomic information back to patients and doctors, "so we already have some of that infrastructure set up, and we are working simultaneously behind the scenes to move that ahead," Murray said.
Along with the clinical report on the findings will come an "action plan" for evaluating the patient and providing any necessary follow-up care. "One of the things we're spending a lot of time on now is designing that safety net and support system, so that the patients and the providers feel confident that if and when they get the results, there will enough expertise around and there will be a system that supports them," Murray said.
It is unclear at this point how many patients will actually receive actionable findings – estimates from smaller exome and genome sequencing studies suggest on the order of 3 to 5 percent – but "when we're getting up into the 10,000 to 100,000 patient range over the course of this project, that will be a lot of people getting relevant data back that we think will improve their care and the care of their families," Murray said.
"If we find a patient, for instance, who has a BRCA or hypertrophic cardiomyopathy gene [mutation], we will be able to help that research participant get the word out to their family members, many of whom are within our healthcare system," he explained.
The plan is also to re-analyze genome data after a period of time in order to take advantage of new research findings. "At this point, we don’t have a specific re-analysis timeline except that we know we'll have to do it," Murray said.
Longer term, patients could benefit from the research on their genomes, both by Regeneron and by Geisinger, who will conduct independent analyses.
Geisinger is still working out specific projects, "but the thought is that we would be able to use the genomic information linked to the patient information and be able to, for instance, look at a subpopulation with diabetes vs. diabetes and hypertension, look at those that have obesity within that population, look at the gender of the population, … and then look for variants that are relevant to whatever parameters are set," Murray said.