In a new paper published June 26 in the Annals of Internal Medicine journal by investigators at Brigham and Women’s Hospital and Harvard Medical School, along with collaborators at Baylor College of Medicine, report the results of the 4 year, NIH–funded MedSeq Project, the first–ever randomized trial conducted to examine the impact of whole genome sequencing in healthy primary care patients.

In the MedSeq Project, 100 healthy individuals and their primary care physicians were enrolled and randomized so that half of the patients received whole genome sequencing and half did not. Nearly 5000 genes associated with rare genetic conditions were expertly analyzed in each sequenced patient, and co–investigators from many different disciplines including clinical genetics, molecular genetics, primary care, ethics, and law were involved in analyzing the results.

Researchers found that among the 50 healthy primary care patients who were randomized to receive genome sequencing, 11 (22 percent) carried genetic variants predicted to cause previously undiagnosed rare disease. Two of these patients were then noted to have signs or symptoms of the underlying conditions, including one patient who had variants causing an eye disease called fundus albipunctatus, which impairs night vision. This patient knew he had difficulty seeing in low light conditions but had not considered the possibility that his visual problems had a genetic cause.

Another patient was found to have a genetic variant associated with variegate porphyria, which finally explained the patient’s and family members’ mysterious rashes and sun sensitivity. The other nine participants had no evidence of the genetic diseases for which they were predicted to be at risk. For example, two patients had variants that have been associated with heart rhythm abnormalities, but their cardiology work–ups were normal. It is possible, but not at all certain, that they could develop heart problems in the future.

“Sequencing healthy individuals will inevitably reveal new findings for that individual, only some of which will have actual health implications,” said lead author Jason Vassy, MD, MPH, a clinician investigator at Brigham and Women’s Hospital, primary care physician at the VA Boston Healthcare System and assistant professor at Harvard Medical School. “This study provides some reassuring evidence that primary care providers can be trained to manage their patients’ sequencing results appropriately, and that patients who receive their results are not likely to experience anxiety connected to those results. Continued research on the outcomes of sequencing will be needed before the routine use of genome sequencing in the primary care of generally healthy adults can be medically justified.”

Primary care physicians received six hours of training at the beginning of the study regarding how to interpret a specially designed, one–page genome testing report summarizing the laboratory analysis.

Researchers note that they analyzed variants from nearly 5000 genes associated with rare genetic diseases. These included single genes causing a significantly higher risk for rare disorders than the low risk variants for common disorders reported by direct–to–consumer genetic testing companies. No prior study has ever examined healthy individuals for pathogenic (high risk) variants in so many rare disease genes.

Additionally, investigators compared the two arms of the study, and found that patients who received genome sequencing results did not show higher levels of anxiety. They did, however, undergo a greater number of medical tests and incurred an average of $350 more in health care expenses in the six months following disclosure of their results.