Signs Point to Expansion of Provider-Initiated Personal Genomic Testing

Since 2013 when the U.S. Food and Drug Administration (FDA) effectively stopped direct-to-consumer personal genomic testing, there has been pent up demand among healthy individuals for testing options to learn about their DNA. Many believe this health-related genetic information has the potential to inform the long-term health care planning of healthy individuals. In early April the FDA granted 23andMe (Mountain View, Calif.) the first authorization to market genetic reports on personal risk for 10 conditions, including late-onset Alzheimer’s disease, Parkinson’s disease, celiac disease, and hereditary thrombophilia (harmful blood clots). “This is an important moment for people who want to know their genetic health risks and be more proactive about their health,” declared 23andMe CEO and co-founder Anne Wojcicki in a statement. “The FDA has embraced innovation and has empowered individuals by authorizing direct access to this information. It is a significant step forward for 23andMe and for the adoption of personal genetics.”

While DTC players are encouraged by the FDA’s action there has been a marked uptick in activity in personal genomics testing ordered by health professionals, with several companies now having such tests commercially available. Some argue this approach will more effectively integrate healthy genome findings (e.g., disease risk and pharmacogenomic findings) into routine care (e.g., screening strategies and prescribing patterns). “Interest in using genetic information to make better health decisions is growing among patients and physicians alike. Proactive genetic testing for healthy adults can be done responsibly if it is based on proven research and focuses on actionable, useful results delivered in a clinical context, with physician guidance throughout the process,” said Robert Nussbaum, M.D., chief medical officer of Invitae, in a statement. “Genetic information can identify disease risk, impact screening decisions, and may lead to the earlier detection and prevention of disease. Our work with our pilot sites is showing how proactive screening can serve as a useful tool at the primary care level.” Healthy Genome Screening Can Detect Meaningful Variants At the American College of Medical Genetics and Genomics (ACMG) annual meeting (Phoenix, Arizona; March 22-24) genomic information company Wuxi NextCODE presented findings from a pilot study of 190 customers (104 male) from the first whole-genome sequencing-based wellness program in China. Saliva or blood samples were tested with Illumina HiSeq X systems to achieve greater than 30X coverage in the company’s CLIA-certified, CAP-accredited sequencing laboratory. Analysis focused on known pathogenic and expected pathogenic variants in genes recommended by ACMG for secondary finding reporting, carrier status for 402 genes of recessive diseases, and genetic risks for 28 common polygenic diseases. Findings were reported to the individuals through post-test counseling. Two individuals had known pathogenic or expected pathogenic variants in ACMG secondary finding genes. For carrier status, 71 samples carried at least one pathogenic or likely pathogenic variant yielding an aggregate carrier frequency of 38.9 percent. On average, four common diseases were reported to each individual (defined as relative risks increased 50 percent above the average population). Developing a Medically Actionable Genetic Screening Panel Also at ACMG, the genetic testing firm Invitae reported on development of their expanded genetic screening panel for healthy individuals. The company’s panel includes more than 120 clinically actionable genes derived from ACMG’s 56 reportable genes plus additional genes that facilitate “more comprehensive testing” in specific clinical areas. The panel also includes 24 genes associated with increased risk for a cancer-related phenotype, 38 genes associated with increased risk for a cardiovascular-related phenotype, and six genes associated with increased risk for other medically actionable disorders. From this expanded list only likely pathogenic or known pathogenic variants are reported.

“Most of the data generated from whole-exome or whole-genome sequencing is not currently interpretable or applicable in the context of a healthy individual, but a focused gene panel presents an opportunity for these individuals to partner with their health care providers to support evidence-based personalized medical care,” writes lead author Eden Haverfield, Ph.D., from Invitae, in the ACMG abstract. “Given the growing interest in and decreasing costs of obtaining this type of health-related genetic information, medically actionable genetic screening represents a notable paradigm shift in clinical genomics as it begins to integrate deeper into routine medical practice, and promotes risk assessment and prevention of serious heritable diseases.” Motivation of Healthy Early Adopters The PeopleSeq Consortium surveyed healthy individuals who underwent personal genome sequencing (PGS) through commercial or research avenues in order to understand their attitudes toward and expectations of PGS. Results were presented at the ACMG annual meeting. Respondents had purchased PGS through Illumina’s Understand Your Genome program, which provides participants with a clinically focused report through an ordering physician, followed by access to their raw genome sequence. This program was introduced at an educational symposium, which explains the fact that most survey respondents were highly educated (doctorate or professional degree).

The top three reasons cited for pursuing PGS were learning about disease risk (23 percent); learning about PGS for professional reasons (15 percent); and curiosity (14 percent). Most individuals reported consulted family members or colleagues, but not medical providers (primary care providers or genetic specialists) before undergoing testing. Additionally, most (62 percent) supported incorporating genomic information into the medical record. Takeaway: While much public attention has focused on direct-toconsumer personal genome testing, there has been a lot of recent activity in the industry to bring physician-ordered PGS to the commercial market. Experts believe healthy individuals have unmet interest in learning about their disease risk and using a physician-involved model may drive greater integration of sequencing results into routine care.