Genome Sequencing Reveals Rare Disease Risk in 1 of 5 Generally Healthy Adults

An analysis of whole-genome sequencing (WGS) in healthy adults in the primary care setting found that 1 in 5 had a previously unrecognized variant associated with a rare disease, according to a study published in Annals of Internal Medicine.

The researchers recruited 9 primary care physicians (PCPs) and 100 generally healthy patients between the ages of 40 and 65 and randomly assigned patients to receive a family history (FH) report alone or in combination with a WGS report. The researchers surveyed patients’ health behavior changes for 6 months after receiving their results and a panel of clinician-geneticists rated the appropriateness of how the PCPs handled the monogenic disease risk results.

“Although the risk-benefit ratio of sequencing is probably favorable in specific clinical contexts, the risks and costs of sequencing might outweigh its benefits for generally healthy persons,” the authors considered.

The study found that 1 in 5 generally healthy adults with WGS had a previously unrecognized variant with potential risk for a Mendelian disease. The variants were associated with rare diseases that many clinicians might be unfamiliar with, but the panel determined that the PCPs were able to manage them.

Despite concerns, the researchers found no evidence that WGS caused patient anxiety or depression, although 30% of patients in the FH group and 41% in the FH and WGS group “reported making health behavior changes related to the results they received.”

The results of the study showed that the PCPs suggested new clinical actions for 16% of patients in the FH group and 34% of patients in the FH and WGS group.

“Although some PCPs may be able to manage the results appropriately, WGS may prompt additional clinical actions without evidence of short-term distress or clinical utility,” the authors concluded.

In an accompanying editorial, Teri A. Manolio, MD, PhD, of the National Human Genome Research Institute, wrote that the findings show that “genetic variants indicative of disease risk, carrier status, or altered response to medications” are frequent, but that PCPs are capable of managing them.

While the study found healthy patients tolerated the information well, many made behavior changes and use and costs did increase in patients with new monogenic disease risk.

“Whether this increased use will truly improve patient outcomes remains to be seen and will be a key factor influencing decisions to reimburse such testing in healthy patients,” she wrote.