Whole-genome sequencing in asymptomatic adults might prevent disease but increase health care use without clinical value.
Dr Jason Vassy and colleagues from Pennsylvania, USA described the effect on clinical care and outcomes of adding whole-genome sequencing to standardized family history assessment in primary care.
The team evaluated 9 primary care physicians, and 100 generally healthy patients recruited at ages 40 to 65 years.
Patients were randomly assigned to receive a family history report alone or in combination with an interpreted whole-genome sequencing report, which included monogenic disease risk results, carrier variants, pharmacogenomic associations, and polygenic risk estimates for cardiometabolic traits.
Each patient met with his or her primary care physicians to discuss the report.
The researchers obtained clinical outcomes and health care use through 6 months from medical records and audio-recorded discussions between primary care physicians and patients.
|Only 4% had evidence of the phenotypes predicted by an monogenic disease risk results|
|Annals of Internal Medicine|
Patients' health behavior changes were surveyed 6 months after receiving results.
A panel of clinician-geneticists rated the appropriateness of how primary care physicians managed MDR results.
The participants' mean age was 55 years, of which 58% were female.
The team found that 22% of family history + whole-genome sequencing patients had new monogenic disease risk results.
The research team observed that only 4% had evidence of the phenotypes predicted by an monogenic disease risk results.
Primary care physicians recommended new clinical actions for 16% of family history patients, and 34% of family history + whole-genome sequencing patients.
The team found that 30% and 41% and family history + whole-genome sequencing patients, respectively, reported making a health behavior change after 6 months.
Geneticists rated primary care physician management of 8 monogenic disease risk results as appropriate and 2 results as inappropriate.
Dr Vassy's team concludes, "Adding whole-genome sequencing to primary care reveals new molecular findings of uncertain clinical utility."
"Nongeneticist providers may be able to manage whole-genome sequencing results appropriately, but whole-genome sequencing may prompt additional clinical actions of unclear value."