Source: Manolio TA. Ann Intern Med. 2017;doi:10.7326/M17-1518.
Vassy JL, et al. Ann Intern Med. 2017;doi:10.7326/M17-0188.
June 26, 2017
2 min read

Whole-genome sequencing shows unclear clinical value in primary care

Source: Manolio TA. Ann Intern Med. 2017;doi:10.7326/M17-1518.
Vassy JL, et al. Ann Intern Med. 2017;doi:10.7326/M17-0188.
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Whole-genome sequencing revealed a risk for rare genetic disease in 20% of healthy primary care patients; however, the technology could lead to increased health care use with limited clinical value in this setting, according to findings published in Annals of Internal Medicine.

“Sequencing is still predominantly the province of genetics specialists, but its expansion in this era of limited health care resources, including access to genetics professionals, evokes concern,” Jason L. Vassy, MD, MPH, SM, from VA Boston Healthcare System, Brigham and Women’s Hospital, Harvard Medical School and Partners HealthCare Personalized Medicine, and colleagues wrote. “The main considerations are whether nongeneticist physicians and [PCPs] can manage genomic information appropriately and the degree to which clinical integration of genomics enables early disease detection and prevention or leads to anxiety and unnecessary and costly follow-up.”

Researchers examined whether adding whole-genome sequencing (WGS) to standardized family history assessment effected clinical care and outcomes in generally health primary care patients.
In this pilot randomized trial, the investigators assessed nine PCPs and 100 patients aged 40 to 65 years at academic primary care practices.

They randomly allocated patients to receive a family history report alone or in combination with an interpreted WGS report. WGS reports included monogenic disease risk results, carrier variants, pharmacogenomic associations and polygenic risk estimates for cardiometabolic traits. Vassy and colleagues used recorded discussions between patients and PCPs, along with medical records, to assess clinical outcomes and health care use through 6 months, and monitored changes in patients’ health behavior 6 months after receiving results.

Analysis showed that 11 patients (22%) in the family history plus WGS group had new monogenic disease risk results, with two patients (4%) showing evidence of the phenotypes predicted by a monogenic disease risk result. PCPs recommended new clinical actions for 34% patients in the family history plus WGS group, compared with 16% of patients with only a family history. After 6 months, 30% of patients with only a family history and 41% of patients with a family history plus WGS reported making a health behavior change, such as a change in exercise, diet, supplements or medication. A panel of clinician-geneticists, asked to assess how PCPs handled monogenic disease risk results, rated PCP management of eight results (73%) as appropriate and two results (18%) as inappropriate.

“The results of this pilot study do not support the use of WGS in primary care but suggest that, if a healthy adult has WGS, some of the resulting increased health care use may be clinically appropriate,” Vassy and colleague wrote. “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.”

In a related editorial, Teri A. Manolio, MD, PhD, a physician and epidemiologist at the National Human Genome Research Institute, wrote that although the study provides reassurance that PCPs can manage WGS information appropriately, family history alone seems more useful, yet is underutilized.

“As perhaps the oldest and simplest truly genome-wide screening tool, [family history] continues to provide a wealth of information, but remains underused,” she wrote. “As we enter the genomic age, the ‘low-tech’ tools that have served us well in the past are important to retain and we should facilitate their use by higher-tech means, such as online data collection.” – by Savannah Demko

Disclosures: Vassy reports no relevant financial disclosures. Please see the full study for a complete list of all other authors’ relevant financial disclosures. Manolio reports that her affiliated department funded and managed the project described by Vassy and colleagues.