Only 1 out of 5 generally healthy patients were found at risk for rare diseases following whole-genome sequencing
Only 1 out of 5 generally healthy patients were found at risk for rare genetic diseases following whole-genome sequencing

The first randomized trial of whole gene sequencing in generally healthy primary care patients has found that 1 out of 5 generally healthy patients were found to be at risk for rare genetic diseases. Of those patients found to be at risk, the majority did not have features associated with the disease, though the group did show slightly incresaed health care costs in the six months after receiving the results

Researchers from Brigham and Women's Hospital and Harvard Medical School, along with collaborators at Baylor College of Medicine, reported that about 22%—11 of 50 patients randomly assigned to receive a whole-genome sequencing (WGS) report as well as a family history report—had a previously unrecognized variant with potential risk for a rare Mendelian disease.

However, only about two of the 11 patients (4%) had a clinically relevant abnormality related to a variant. A total 100 generally healthy patients aged 40 to 65 years were recruited and randomized in the pilot study, “The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients: A Pilot Randomized Trial,” published in Annals of Internal Medicine.

More sobering, healthcare costs for the patients in the sequenced group averaged about $300 greater per patient in the 6 months following disclosure, according to the study.

In an accompanying editorial, Teri Manolio, M.D., Ph.D., director of the Division of Genomic Medicine at the NIH’s National Human Genome Research Institute, said the results posed challenges for advocates of incorporating more genome sequencing in clinical practice: “The lack of evidence of utility will be one of the hardest [obstacles] to overcome, but this pilot study has provided valuable reassurances and useful tools for taking that next step in the sequence of implementing WGS in clinical care.”

Yet in their study, the researchers suggested that more research with larger sample sizes and longer follow up is needed to determine whether and how whole genome sequencing can be integrated into the care of healthy individuals.

The study offered data seeming to support such integration, by finding that primary care physicians were generally able to manage findings appropriately—and that whole-genome sequencing did not seem to cause patient anxiety or depression. Thirty percent of family history-alone patients, and 41% of patients receiving WGS plus family history, reported making health behavior changes 6 months after receiving results.

“Adding WGS to primary care reveals new molecular findings of uncertain clinical utility. Nongeneticist providers may be able to manage WGS results appropriately, but WGS may prompt additional clinical actions of unclear value,” the researchers wrote.

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