Sequencing finds rare genetic disease risk in one out of five healthy adults

Whole-genome sequencing involves evaluating a patient's DNA to identify risk for genetic conditions and undiagnosed diseases. Many health care systems are moving toward more widespread adoption of clinical sequencing with the hope of predicting and preventing disease. The concern is whether primary care physicians who are not geneticists will be able to manage genomic information appropriately, or if adding sequencing to standard primary care will lead to patient anxiety and increased health care use and cost.

Researchers from Brigham and Women's Hospital and Harvard Medical School, along with collaborators at Baylor College of Medicine, conducted the first-ever randomized trial to examine the impact of whole-genome sequencing in healthy primary care patients. One hundred participants were randomly assigned to receive a family history report alone (n = 50) or in combination with a whole-genome sequencing report (n = 50). They found that about 22 percent of generally healthy adult patients with whole genome sequencing results had a previously unrecognized variant with potential risk for a rare Mendelian disease. However, only about 4 percent had a clinically relevant abnormality related to a variant. Primary care physicians were generally able to manage findings appropriately. Investigators also found that whole-genome sequencing did not seem to cause patient anxiety or depression, but considerable proportions of patients in both groups reported making health behavior changes related to the results they received. Health care costs in the 6 months following disclosure averaged about $300 greater per patient for those in the sequenced group.

While the results are promising, the investigators suggest 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.