Christensen, Kurt D.

Abstract Purpose Elective genomic sequencing (EGS) returns monogenic disease findings in multiple genes, including potentially novel variants, and may also provide participants with carrier status, pharmacogenomic and other health-related information. The PeopleSeq Study assessed participants’ motivations for and concerns about EGS and the associated clinical and psychosocial outcomes across diverse EGS providers. Methods We administered a shared questionnaire to participants who chose to undergo EGS via 18 academic, clinical, or commercial EGS platforms. Results We enrolled 1575 participants, of whom 1147 (72.8%) completed a questionnaire after receiving their EGS results. A majority (60.3%) of the participants who completed a post-result questionnaire self-reported receiving results they assessed as important, including negative findings, and 75.9% reported a form of health-related utility. Among a subset (19.4%) who shared their EGS reports, 16.6% (37 of n =223) received a monogenic finding and self-reported results deemed “important” were consistent with EGS reports. Most participants (74.1%) discussed their results with their family, but fewer discussed their results with a healthcare provider other than the site team (41.7%) or had one or more medical visits as a direct result of their EGS testing (23.1%). Participants expressed diverse motivations for EGS, with 91.4% expressing interest in their personal disease risk and 54% who expressed quasi-indication-based motivations related to family medical history. Individuals motivated by family history reported important results at a significantly higher rate. Conclusions Early adopters of EGS are motivated by general interest in their health as well as quasi-indication-based considerations such as family history. A majority of participants learned results they considered medically important, but a much smaller segment engaged healthcare providers with their results.

Abstract The public health impact of genomic screening can be enhanced by cascade testing. However, cascade testing depends on communication of results to family members. While the barriers and facilitators of family communication have been researched following clinical genetic testing, the factors impacting the dissemination of genomic screening results are unknown. Using the pragmatic Electronic Medical Records and Genomics Network‐3 (eMERGE‐3) study, we explored the reported sharing practices of participants who underwent genomic screening across the United States. Six eMERGE‐3 sites returned genomic screening results for mostly dominant medically actionable disorders and surveyed adult participants regarding communication of results with first‐degree relatives. Across the sites, 279 participants completed a 1‐month and/or 6‐month post‐results survey. By 6 months, only 34% of the 156 respondents shared their results with all first‐degree relatives and 4% did not share with any. Over a third (39%) first‐degree relatives were not notified of the results. Half (53%) of participants who received their results from a genetics provider shared them with all first‐degree relatives compared with 11% of participants who received their results from a non‐genetics provider. The most frequent reasons for sharing were a feeling of obligation (72%) and that the information could help family members make medical decisions (72%). The most common reasons indicated for not sharing were that the family members were too young (38%), or they were not in contact (25%) or not close to them (25%). These data indicate that the professional returning the results may impact sharing patterns, suggesting that there is a need to continue to educate healthcare providers regarding approaches to facilitate sharing of genetic results within families. Finally, these data suggest that interventions to increase sharing may be universally effective regardless of the origin of the genetic result.

Background: Perceived personal control (PPC) represents the belief that a person can alter his/her own situation or state. Higher PPC has been associated with increased health-related quality of life and helps facilitate healthy behavioral changes. We investigated whether disclosure of coronary heart disease (CHD) genetic risk influences PPC and genetic counseling satisfaction (GCS) in the myocardial infarction genes (MI-GENES) study, a randomized controlled trial of disclosing genetic risk of CHD. Methods: Participants (40-65 year-old, at intermediate 10-year CHD risk, and not on statins) were randomized to receive estimated 10-year risk of CHD based on their Framingham Risk Score (FRS) or FRS plus a 28 SNP genetic risk score (FRS*GRS). CHD risk was disclosed in each arm by a genetic counselor during a 30-minute scripted session that included a discussion of the impact of family history on CHD risk. For FRS*GRS participants, the genetic counselor also reviewed how their genetic risk score altered their FRS. Each participant then met with a physician to engage in shared-decision making regarding the need for statin therapy. Afterwards, study participants were asked to complete validated surveys to assess PPC and GCS. The 9-item PPC questionnaire was scored 0-9, with higher scores indicating greater control beliefs. The 5-item GCS questionnaire was scored 0-10, with greater scores indicating greater satisfaction with the disclosure session. Results: 207 patients (mean age 58.8±5 years, 46.7% males) were randomized to receive either FRS or FRS*GRS. Patients randomized to receive FRS*GRS had higher PPC compared to FRS although the absolute difference was small (8.85±0.77 vs. 8.54±1.31, P=0.016). Patients randomized to receive FRS*GRS also had a higher GCS score than FRS patients (9.08±2.67 vs. 8.3±3.67, P=0.050]. Conclusions: Disclosure of genetic risk for CHD did not adversely affect PPC or GCS. In fact, patients who received CHD genetic risk information had higher PPC and GCS. Our findings suggest that disclosure of CHD genetic risk is appreciated by patients and may empower them to improve health-related behaviors.

A goal of the 3rd phase of the Electronic Medical Records and Genomics (eMERGE3) Network was to examine the return of results (RoR) of actionable variants in more than 100 genes to consenting participants and their healthcare providers. Each of the 10 eMERGE sites developed plans for three essential elements of the RoR process: Disclosure to the participant, notification of the health care provider, and integration of results into the electronic health record (EHR). Procedures and protocols around these three elements were adapted as appropriate to individual site requirements and limitations. Detailed information about the RoR procedures at each site was obtained through structured telephone interviews and follow-up surveys with the clinical investigator leading or participating in the RoR process at each eMERGE3 institution. Because RoR processes at each of the 10 sites allowed for taking into account differences in population, disease focus and institutional requirements, significant heterogeneity of process was identified, including variability in the order in which patients and clinicians were notified and results were placed in the EHR. This heterogeneity in the process flow for eMERGE3 RoR reflects the “real world” of genomic medicine in which RoR procedures must be shaped by the needs of the patients and institutional environments.

We investigated whether disclosure of coronary heart disease (CHD) genetic risk influences perceived personal control (PPC) and genetic counseling satisfaction (GCS). Participants (n = 207, age: 45–65 years) were randomized to receive estimated 10‐year risk of CHD based on a conventional risk score (CRS) with or without a genetic risk score (GRS). Risk estimates were disclosed by a genetic counselor who also reviewed how GRS altered risk in those randomized to CRS+GRS. Each participant subsequently met with a physician and then completed surveys to assess PPC and GCS. Participants who received CRS+GRS had higher PPC than those who received CRS alone although the absolute difference was small (25.2 ± 2.7 vs 24.1 ± 3.8, p = 0.04). A greater proportion of CRS+GRS participants had higher GCS scores (17.3 ± 5.3 vs 15.9 ± 6.3, p = 0.06). In the CRS+GRS group, PPC and GCS scores were not correlated with GRS. Within both groups, PPC and GCS scores were similar in patients with or without family history (p = NS). In conclusion, patients who received their genetic risk of CHD had higher PPC and tended to have higher GCS. Our findings suggest that disclosure of genetic risk of CHD together with conventional risk estimates is appreciated by patients. Whether this results in improved outcomes needs additional investigation.