NEW YORK (GenomeWeb) – Geisinger investigators have been able to return secondary genomic findings to most participants in its MyCode Community Health Initiative in whom they found pathogenic variants.
The MyCode initiative launched in 2007 to build a repository of patient samples to fuel research studies and later expanded into a collaboration between Geisinger and the Regeneron Genomics Center to sequence participating patients.
The investigators also began screening patients' genomes for pathogenic or likely pathogenic variants associated with monogenic conditions and developed a pipeline to return results from their research effort to clinicians and patients. As they reported in the American Journal of Human Genetics today, they used this model to disclose secondary genomic findings to 95 percent of patients with such results.
"The early stages of this program have been successful at reaching subjects and their providers about results, and demonstrate the feasibility of incorporating genomic sequence risk information into clinical care management," Geisinger's Michael Murray and his colleagues wrote in their paper.
In 2013, the American College of Medical Genetics and Genomics issued guidelines that recommended clinical testing labs report incidental findings in 56 genes — later increased to 59 genes — from clinical exome and genome sequencing tests, even when those genes were not related to the reason for testing. Murray and his colleagues noted that while there are no similar guidelines regarding research-generated results, they added there has been growing interest in providing research participants with clinically relevant results.
The investigators followed three guiding principles for their model for returning secondary findings: careful selection of medically actionable genes, stringent variant interpretation, and a supportive clinical result return process.
In particular, the Geisinger team developed a list of 76 genes — which includes all the genes on the ACMG list — linked to 27 conditions to incorporate into its analyses. These genes are associated with cancer-predisposing syndromes and cardiovascular conditions, among others.
In their model, the initial variant call is made from research-generated whole-exome sequencing data. To confirm it in a CLIA lab setting, the researchers either collected a second DNA samples or used a second aliquot from a stored sample for Sanger sequencing-based confirmation. Only variants classified as pathogenic or likely pathogenic are returned.
The investigators also relied on a data broker to act as a gatekeeper between the participants' de-identified study sample and personal identifiers.
Once generated, the clinical lab results are shared with the study team and reviewed before the participants' primary care physicians are notified. They noted that they informed physicians first based on feedback from providers, a move they said was approved by patients.
The patient is then also notified that there is a result through the portal or by a letter. They can then learn the nature of the result by phone or letter and choose whether or not to follow up with a provider.
Following this model, Geisinger investigators have uncovered 546 pathogenic or likely pathogenic variants within 542 participants out of a total 200,000 participants. Of these 542 participants, 511 individuals had direct contact with the GSCP team as part of the results reporting process and a further 31 mentioned their result to their primary care physician, according to documentation in the EHRs.
Overall, the Geisinger team reported it was able to successfully return results to 95 percent of individuals. This notification process, they noted, took an average 1.62 phone calls per participant.
This approach, Murray and his colleagues wrote, can be adapted for use by other institutions.
"Although the model applied here is specific to generating results from genomic screening, the same broad principles can be applied to other programs that search existing data for meaningful information," they added.