As increased accessibility to genetic testing contributes to finding more individuals with genetic predispositions to a specific conditions or diseases, National Institutes of Health-sponsored networks grow in importance when considering the identification and subsequent management of these conditions. The American College of Genetics and Genomics (ACMG) designated 59 genes (this is now higher with subsequent versions of the guideline) as highly actionable owing to availability of effective medical management guidelines for individuals with detected disease-causing variants in one of these genes. Because the identification of hereditary disorders can greatly assist in patient monitoring and treatment for many diseases (eg, use of PARP inhibitors in patients with specific breast cancer pathogenic variants in BRCA1 or BRCA2), streamlining the procedure for genomic testing and strategies for return of results (RoRs) can improve patient experiences. The aim of this study was to use one such network, the Electronic Medical Records and Genomics (eMERGE) Network, to analyze the procedures of genomic testing and RoRs of significant variants in genes associated with adult-onset disease in various institutions, thereby evaluating the RoR process (including methods for RoR, consent, result disclosure to participants, informing health care providers, and data uploading to electronic health records [EHRs]). One of the goals of genomic medicine is to provide tailored management and surveillance for individuals with a highly penetrant disease-causing genetic variant. Connecting genomic information to a national database such as eMERGE3 instills the hope of decreasing or ameliorating associated disease by establishing a unified slate of best practices for various genetic conditions. This study and experience of RoR via the eMERGE3 Network was meant to guide and inform future genomic research projects (along with efforts of implementation). The eMERGE3 study enrolled approximately 25,000 participants from 10 different health care systems, through which sequencing of approximately 100 actionable genes took place. In all, 1444 had at least 1 pathogenic or likely pathogenic variant in a significant gene eligible for RoR; 35 had variants in 2 different genes. An overall frequency of 5.7% of pathogenic or likely pathogenic variants among eMERGE participants was demonstrated, although it ranged from 2.8% to 10.3% at individual sites based on initial sampling methods and site-specific criteria for RoR. Of the 1444 participants with at least 1 variant, 1077 were disclosed to the participant (74.6%). Adult populations had a results disclosure rate of 82.5% (ranging from 24.7% to 97.5%) across cohorts and clinical sites, whereas pediatric participants had a lower results disclosure rate of 24.2%, ranging between 20.9% and 83.3%. Sites not only differed in policies as to whether or not participants were required to have results disclosed, but they also varied in the method of communication of results. Various methods included in-person appointments with a medical geneticist and/or genetic counselor, phone calls, use of a patient portal in the EHR, and use of US postal mail. These varying methods of disclosure are thought to be an important contributing factor to rates of results disclosure. One notable finding was that RoR processes did not necessarily imply that participants received genetic counseling. Across the eMERGE3 Network, a total of 38.9% of 1444 participants with pathogenic or likely pathogenic variants received their results and genetic counseling. However, the number of participants who actually received genetic counseling is likely higher as some participants had prior knowledge of their genetic diagnoses and therefore previous genetic counseling for their disease-associated variant. Limitations of the study results must be understood in the context of the eMERGE3 Network. First, owing to the heterogeneous nature of 10 eMERGE site participant populations, the 5.8% percentage of variants reported here is notably higher than the frequency of secondary findings reported previously (3%). Second, the focus of this project was a systems-based impact and effectiveness of RoR processes. Downstream impacts of these processes (ie, health care services/cascade testing) are beyond this study's scope. Lastly, observed variability emerged due to differences of individual site RoR processes, but this demonstrates clinical utility of genomic screening and can guide future research investigations relating to clinical care implementation. Overall, the eMERGE3 study demonstrated that issues of consent, engagement, contact, and participation in genetic counseling should be considered before broader implementation of DNA sequence results into health care, as demonstrated by the barriers experienced by sites and adaptations to the eMERGE3 RoR processes.
|Original language||English (US)|
|Number of pages||4|
|Journal||Obstetrical and Gynecological Survey|
|State||Published - Nov 1 2022|
ASJC Scopus subject areas
- Obstetrics and Gynecology