Addressing underrepresentation in genomics research through community engagement.

The vision of the American Society of Human Genetics (ASHG) is that people everywhere will realize the benefits of human genetics and genomics. Implicit in that vision is the importance of ensuring that the benefits of human genetics and genomics research are realized in ways that minimize harms and maximize benefits, a goal that can only be achieved through focused efforts to address health inequities and increase the representation of underrepresented communities in genetics and genomics research. This guidance is intended to advance community engagement as an approach that can be used across the research lifecycle. Community engagement uniquely offers researchers in human genetics and genomics an opportunity to pursue that vision successfully, including by addressing underrepresentation in genomics research.

Engagement and return of results preferences among a primarily African American genomic sequencing research cohort.

Genomics researchers are increasingly interested in what constitutes effective engagement of individuals from underrepresented groups. This is critical for longitudinal projects needed to inform the implementation of precision medicine. Return of results is one opportunity for engagement. The aims of this study were to determine participant perspectives on optimal engagement strategies and priorities for return of results and the extent to which focus groups were an effective modality for gathering input on these topics. We conducted six professionally moderated focus groups with 49 participants in a genomics research study. Transcripts from audio-recorded sessions were coded by two researchers and themes were discussed with the wider research team. All groups raised the issue of mistrust. Individuals participated nonetheless to contribute their perspectives and benefit their community. Many group members preferred engagement modalities that are offered to all participants and allow them to share the nuances of their perspectives over the use of participant representatives and surveys. All groups created a consensus ranking for result return priorities. Results for life-threatening conditions were the highest priority to return, followed by those related to treatable conditions that affect physical or mental health. We advocate for engagement strategies that reach as many participants as possible and allow them to share their perspectives in detail. Such strategies are valued by participants, can be effective for developing return of results policies, and may help institutions become more trustworthy.

The Parent PrU: A measure to assess personal utility of pediatric genomic results.

PURPOSE: We aimed to adapt and validate an existing patient-reported outcome measure, the personal-utility (PrU) scale, for use in the pediatric genomic context. METHODS: We adapted the adult version of the PrU and obtained feedback from 6 parents whose child had undergone sequencing. The resulting measure, the Parent PrU, was administered to parents of children in 4 pediatric cohorts of the Clinical Sequencing Evidence-Generating Research consortium after they received their children's genomic results. We investigated the measure's structural validity and internal consistency. RESULTS: We conducted a principal-axis factor analysis with oblimin rotation on data from 755 participants to determine structural validity. These analyses yielded a 3-factor solution, accounting for 76% of the variance in the 16 items. We used Cronbach's α to assess the internal consistency of each factor: (1) child benefits (α = .95), (2) affective parent benefits (α = .90), and (3) parent control (α = .94). CONCLUSION: Our evidence suggests that the Parent PrU scale has potential as a measure for assessing parent-reported personal utility of their children's genomic results. Additional research is needed to further validate the Parent PrU scale, including by comparing its findings with utility assessments reported by clinicians and children themselves.

Parents' preferences for receiving and discussing prognostic genetic information regarding their children's neurodevelopmental condition: A qualitative study.

AIM: To investigate parents' preferences and motivations for receiving and discussing prognostic genetic test results. METHOD: We used a cross-sectional, interpretive description qualitative study design. We collected data through semi-structured interviews with Australian parents, which we analysed using reflexive thematic analysis. RESULTS: Parents (n = 32) had a child or children with a genetic neurodevelopmental condition, such as fragile X syndrome, DiGeorge (22q11.2 deletion) syndrome, or Angelman syndrome. Parents of mildly impacted or older children were tolerant to prognostic uncertainty. Parents found conversations about their child's prognosis emotional and preferred to discuss their child's potential strengths and challenges. While most were enthusiastic about prognostic tests and described many motivations for testing, the potential for prognostic information to contribute to a loss of hope and stigmatizing societal views were also discussed. INTERPRETATION: Parents had mixed preferences and motivations for acquiring prognostic genetic information about their child, contrasting evidence in other contexts such as cancer where parents typically have minimal tolerance of uncertainty. Health professionals should consider strength-based framing of prognostic information gained from current and emerging technologies when returning results to families. WHAT THIS PAPER ADDS: Parents had varied views about receiving prognostic information on their children's neurodevelopmental condition. Some parents preferred prognostic uncertainty about their children's genetic neurodevelopmental condition.

Race, ethnicity, and ancestry reporting in genetic counseling research: A focused mapping review and synthesis.

Studies on the use of Race, Ethnicity, and Ancestry (REA) concepts and terms in genetic research are limited. We aimed to describe the collection, reporting, and use of REA data in genetic counseling research. We undertook a focused mapping review and synthesis of the Journal of Genetic Counseling 2021 publications. We used a mapping proforma based on the Race, Ethnicity, And Culture in Health checklist to extract data. Of the 177 screened articles, 132 met our inclusion criteria of reporting primary data about participants. The sample REA characteristics were described in 80 (61%) articles, with 6% providing a definition or conceptualization of the REA term/s used and 23% including a rationale for their study in terms of REA factors. Group labels were most often reported using population descriptors, such as "race," "ethnicity," "race/ethnicity," and "ancestry." Several group labels were used under different population descriptors. For instance, the group labels "White" and "Asian" were used under all population descriptors. Most studies (79%) ascertained REA characteristics by participants' self-report. Three (15%) of the 20 qualitative studies mentioned the relevance of the interviewers' REA characteristics in relation to the participants' REA characteristics. Of the 55 quantitative studies, 19 (35%) used REA factors in the data analysis. Of the 80 articles describing the sample REA characteristics, 20% referred moderately or a great deal to any REA factors in the results interpretation, 46% acknowledged the REA factors in the study limitations, and 15% discussed the implications of REA reporting for genetic counseling practice. Our review documents extensive variation in how sample REA characteristics are described and used in genetic counseling research. Our findings provide a baseline against which to evaluate the effects of guidelines and recommendations for the collection, responsible use, and report of participants' REA characteristics in genetic counseling research.

The PrU: Development and validation of a measure to assess personal utility of genomic results.

PURPOSE: People report experiencing value from learning genomic results even in the absence of clinically actionable information. Such personal utility has emerged as a key concept in genomic medicine. The lack of a validated patient-reported outcome measure of personal utility has impeded the ability to assess this concept among those receiving genomic results and evaluate the patient-perceived value of genomics. We aimed to construct and psychometrically evaluate a scale to measure personal utility of genomic results-the Personal Utility (PrU) scale. METHODS: We used an evidence-based, operational definition of personal utility, with data from a systematic literature review and Delphi survey to build a novel scale. After piloting with 24 adults, the PrU was administered to healthy adults in a Clinical Sequencing Evidence-Generating Research Consortium study after receiving results. We investigated the responses using exploratory factor analysis. RESULTS: The exploratory factor analysis (N = 841 participants) resulted in a 3-factor solution, accounting for 74% of the variance in items: (1) self-knowledge (α = 0.92), (2) reproductive planning (α = 0.89), and (3) practical benefits (α = 0.91). CONCLUSION: Our findings support the use of the 3-factor PrU to assess personal utility of genomic results. Validation of the PrU in other samples will be important for more wide-spread application.

Models of communication for polygenic scores and associated psychosocial and behavioral effects on recipients: A systematic review.

PURPOSE: This study aimed to systematically review current models for communicating polygenic scores (PGS) and psycho-behavioral outcomes of receiving PGSs. METHODS: Original research on communicating PGSs and reporting on psycho-behavioral outcomes was included. Search terms were applied to 5 databases and were limited by date (2009-2021). RESULTS: In total, 28 articles, representing 17 studies in several disease settings were identified. There was limited consistency in PGS communication and evaluation/reporting of outcomes. Most studies (n = 14) presented risk in multiple ways (ie, numerically, verbally, and/or visually). Three studies provided personalized lifestyle advice and additional resources. Only 1 of 17 studies reported using behavior change theory to inform their PGS intervention. A total of 8 studies found no evidence of long-term negative psychosocial effects up to 12 months post result. Of 14 studies reporting on behavior, 9 found at least 1 favorable change after PGS receipt. When stratified by risk, 7 out of 9 studies found high PGS was associated with favorable changes including lifestyle, medication, and screening. Low-risk PGS was not associated with maladaptive behaviors (n = 4). CONCLUSION: PGS has the potential to benefit health behavior. High variability among studies emphasizes the need for developing standardized guidelines for communicating PGSs and evaluating psycho-behavioral outcomes. Our findings call for development of best communication practices and evidence-based interventions informed by behavior change theories.

Motivations to learn genomic information are not exceptional: Lessons from behavioral science.

Whether to undergo genome sequencing in a clinical or research context is generally a voluntary choice. Individuals are often motivated to learn genomic information even when clinical utility-the possibility that the test could inform medical recommendations or health outcomes-is low or absent. Motivations to seek one's genomic information can be cognitive, affective, social, or mixed (e.g., cognitive and affective) in nature. These motivations are based on the perceived value of the information, specifically, its clinical utility and personal utility. We suggest that motivations to learn genomic information are no different from motivations to learn other types of personal information, including one's health status and disease risk. Here, we review behavioral science relevant to motivations that may drive engagement with genome sequencing, both in the presence of varying degrees of clinical utility and in the absence of clinical utility. Specifically, we elucidate 10 motivations that are expected to underlie decisions to undergo genome sequencing. Recognizing these motivations to learn genomic information will guide future research and ultimately help clinicians to facilitate informed decision making among individuals as genome sequencing becomes increasingly available.

Extending an Antiracism Lens to the Implementation of Precision Public Health Interventions.

Precision public health holds promise to improve disease prevention and health promotion strategies, allowing the right intervention to be delivered to the right population at the right time. Growing concerns underscore the potential for precision-based approaches to exacerbate health disparities by relying on biased data inputs and recapitulating existing access inequities. To achieve its full potential, precision public health must focus on addressing social and structural drivers of health and prominently incorporate equity-related concerns, particularly with respect to race and ethnicity. In this article, we discuss how an antiracism lens could be applied to reduce health disparities and health inequities through equity-informed research, implementation, and evaluation of precision public health interventions. (Am J Public Health. 2023;113(11):1210-1218. https://doi.org/10.2105/AJPH.2023.307386).

Views and experiences of palliative care clinicians in addressing genetics with individuals and families: a qualitative study.

PURPOSE: A proportion of people with palliative care needs unknowingly have a genetic predisposition to their disease, placing relatives at increased risk. As end-of-life nears, the opportunity to address genetics for the benefit of their family narrows. Clinicians face numerous barriers addressing genetic issues, but there is limited evidence from the palliative care clinician perspective. Our aims are to (1) explore the views and experiences of palliative care clinicians in addressing genetics with patients and their families and (2) generate suggested strategies that support integration of genetics into palliative care. METHODS: An interpretive descriptive qualitative study using semi-structured interviews with palliative care doctors and nurses (N = 14). RESULTS: Three themes were identified: (1) Harms and benefits of raising genetics: a delicate balancing act, (2) Navigating genetic responsibility within the scope of palliative care and (3) Overcoming practice barriers: a multipronged approach. Participants described balancing the benefits of addressing genetics in palliative care against potential harms. Responsibility to address genetic issues depends on perceptions of relevance and the scope of palliative care. Suggestions to overcome practice barriers included building genetic-palliative care relationships and multi-layered genetics education, developing clinical resources and increasing organisational support. CONCLUSIONS: Integrating aspects of genetics is feasible, but must be balanced against potential harms and benefits. Palliative care clinicians were uncertain about their responsibility to navigate these complex issues to address genetics. There are opportunities to overcome barriers and tailor support to ensure people nearing end-of-life have a chance to address genetic issues for the benefit of their families.

Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot.

While consensus regarding the return of secondary genomic findings in the clinical setting has been reached, debate about such findings in the research setting remains. We developed a hybrid, research-clinical translational genomics process for research exome data coupled with a CLIA-validated secondary findings analysis. Eleven intramural investigators from ten institutes at the National Institutes of Health piloted this process. Nearly 1,200 individuals were sequenced and 14 secondary findings were identified in 18 participants. Positive secondary findings were returned by a genetic counselor following a standardized protocol, including referrals for specialty follow-up care for the secondary finding local to the participants. Interviews were undertaken with 13 participants 4 months after receipt of a positive report. These participants reported minimal psychologic distress within a process to assimilate their results. Of the 13, 9 reported accessing the recommended health care services. A sample of 107 participants who received a negative findings report were surveyed 4 months after receiving it. They demonstrated good understanding of the negative secondary findings result and most expressed reassurance (64%) from that report. However, a notable minority (up to 17%) expressed confusion regarding the distinction of primary from secondary findings. This pilot shows it is feasible to couple CLIA-compliant secondary findings to research sequencing with minimal harms. Participants managed the surprise of a secondary finding with most following recommended follow up, yet some with negative findings conflated secondary and primary findings. Additional work is needed to understand barriers to follow-up care and help participants distinguish secondary from primary findings.

Dyadic concordance and associations of beliefs with intentions to learn carrier results from genomic sequencing.

Although romantic couple concordance has been demonstrated across a wide array of health behaviors, little research has examined dyadic concordance in health beliefs. This study examined the extent to which cohabitating romantic dyads' attitudes and beliefs coincide (i.e., dyadic concordance) in addition to how well they predict intentions to learn genomic sequencing results. The actor-partner interdependence model was applied to cross-sectional data from 81 dyads in an exome sequencing study who were surveyed about their risk perceptions, worry, information avoidance, attitudes, and intentions toward learning carrier results. Information avoidance tendencies were positively correlated between partners, but there was low concordance on other beliefs. Individuals' attitudes and information avoidance predicted their own intentions to learn results. Additionally, partners' information avoidance tendencies predicted their partner's intentions to learn results. Future research should explore mechanisms through which one's partner's information avoidance may affect one's own intentions and behaviors.

Preferences for and acceptability of receiving pharmacogenomic results by mail: A focus group study with a primarily African-American cohort.

Although genetic counseling is traditionally done through in-person, one-on-one visits, workforce shortages call for efficient result return mechanisms. Studies have shown that telephone and in-person return of cancer genetic results are equivalent for patient outcomes. Few studies have been conducted with other modes, result types or racially diverse participants. This study explored participants' perspectives on receiving pharmacogenomic results by mail. Two experienced moderators facilitated six focus groups with 49 individuals who self-identified primarily as African-American and consented to participate in a genome sequencing cohort study. Participants were given a hypothetical pharmacogenomic result report (positive for c.521T>C in SLCO1B1). An accompanying letter explained that the result was associated with statin intolerance along with a recommendation to share it with one's doctor and immediate relatives. Participants reacted to the idea of receiving this type of result by mail, discussing whether the letter's information was sufficient and what they predicted they would do with the result. Two researchers coded the focus group transcripts and identified themes. Many participants thought that it was appropriate to receive the result through the mail, but some suggested a phone call alerting the recipient to the letter. Others emphasized that although a letter was acceptable for disclosing pharmacogenomic results, it would be insufficient for what they perceived as life-threatening results. Most participants found the content sufficient. Some participants suggested resources about statin intolerance and warning signs be added. Most claimed they would share the result with their doctor, yet few participants offered they would share the result with their relatives. This exploratory study advances the evidence that African-American research participants are receptive to return of certain genetic results by approaches that do not involve direct contact with a genetic counselor and intend to share results with providers. ClinSeq: A Large-Scale Medical Sequencing Clinical Research Pilot Study (NCT00410241).

Ethnic identity and engagement with genome sequencing research.

PURPOSE: We examined the role of ethnic identity (which measures the degree to which individuals identify with their ethnic group) in beliefs about, and intentions to learn, genomic results. METHODS: A longitudinal cohort was recruited to implement genome sequencing among healthy participants self-identifying as African, African American, or Afro-Caribbean, 40-65 years old (n = 408). Before receiving genomic results, participants completed a survey assessing social and behavioral constructs related to health, genomics, and ethnic identity. RESULTS: Ethnic identity was positively correlated with perceived value of genomic results and expected benefits from genomic research participation. Among participants with stronger ethnic identity, cognitive beliefs (perceived value of results [b = 0.63, 95% confidence interval: 0.29, 0.98, p < 0.001] and expected benefits from genomic research participation [b = 0.32, 95% confidence interval: 0.12, 0.53, p = 0.002]) were associated with intentions to receive results. Among those with weaker ethnic identity, there was no such association. CONCLUSION: Individuals with stronger ethnic identity seem to attend more to cognitive beliefs such as the value of genomic results when deliberating receipt of results compared with those with weaker ethnic identity. Understanding ethnic identity variation and its influence on genome sequencing perceptions and intentions can inform future research opportunities using ethnic identity to explore specific practical, clinical questions.

Secondary findings from clinical genomic sequencing: prevalence, patient perspectives, family history assessment, and health-care costs from a multisite study.

PURPOSE: Clinical sequencing emerging in health care may result in secondary findings (SFs). METHODS: Seventy-four of 6240 (1.2%) participants who underwent genome or exome sequencing through the Clinical Sequencing Exploratory Research (CSER) Consortium received one or more SFs from the original American College of Medical Genetics and Genomics (ACMG) recommended 56 gene-condition pair list; we assessed clinical and psychosocial actions. RESULTS: The overall adjusted prevalence of SFs in the ACMG 56 genes across the CSER consortium was 1.7%. Initially 32% of the family histories were positive, and post disclosure, this increased to 48%. The average cost of follow-up medical actions per finding up to a 1-year period was $128 (observed, range: $0-$678) and $421 (recommended, range: $141-$1114). Case reports revealed variability in the frequency of and follow-up on medical recommendations patients received associated with each SF gene-condition pair. Participants did not report adverse psychosocial impact associated with receiving SFs; this was corroborated by 18 participant (or parent) interviews. All interviewed participants shared findings with relatives and reported that relatives did not pursue additional testing or care. CONCLUSION: Our results suggest that disclosure of SFs shows little to no adverse impact on participants and adds only modestly to near-term health-care costs; additional studies are needed to confirm these findings.

Correction: Secondary findings from clinical genomic sequencing: prevalence, patient perspectives, family history assessment, and health-care costs from a multisite study.

The originally published version of this Article contained errors in Fig. 2. The numbers below the black arrowheads were incorrect; please see incorrect Figure in associated Correction. These errors have now been corrected in the PDF and HTML versions of the Article.

Managing the need to tell: Triggers and strategic disclosure of thalassemia major in Singapore.

This study explored patients' experiences and perceptions of living with thalassemia (an inherited hematologic disorder), perceptions of social stigma, and impact on disclosure decision-making. Semistructured, in-person interviews were conducted in Singapore with 30 individuals: 16 thalassemia major patients and 14 parents of children with thalassemia. Findings were indicative of felt or enacted stigma that may have influenced disclosure decisions. Although affected individuals commonly disclosed their thalassemia diagnosis to family members, they either downplayed the condition with or avoided disclosure to unrelated individuals. Disclosure outside the family occurred only in response to triggers, such as questions about absences due to medical care. Health professionals should provide anticipatory guidance about disclosure strategies when managing individuals with thalassemia.

Genetic counseling, genetic testing, and risk perceptions for breast and colorectal cancer: Results from the 2015 National Health Interview Survey.

We examined what proportion of the U.S. population with no personal cancer history reported receiving either genetic counseling or genetic testing for cancer risk, and also the association of these behaviors with cancer risk perceptions. We used data from the 2015 National Health Interview Survey. Objective relative risk scores for breast (women) and colorectal (men and women) cancer risk were generated for individuals without a personal history of cancer. Participants' risk perceptions were compared with their objective relative risk. Of 12,631 women, 1.2% reported receiving genetic counseling and 0.8% genetic testing for hereditary breast cancer risk. Of 15,085 men and women, 0.8% reported receiving genetic counseling and 0.3% genetic testing for hereditary colorectal cancer risk. Higher breast cancer risk perception was associated with genetic counseling (OR: 4.31, 95%CI: 2.56, 7.26) and testing (OR: 3.56, 95%CI: 1.80, 7.03). Similarly, higher perception of colorectal cancer risk was associated with genetic counseling (OR: 5.04, 95%CI: 2.57, 9.89) and testing (OR: 5.92, 95%CI: 2.40, 14.63). A higher proportion of individuals with colorectal cancer risk perceptions concordant with their objective risk (vs. discordant) had undergone genetic counseling or testing for colorectal cancer risk. Concordant risk perceptions for breast cancer were not associated with breast cancer genetic counseling or testing. Given frequent dialogue about implementing population level programs involving genetic services for cancer risk, policy makers and investigators should consider the role of risk perceptions in the effectiveness and design of such programs and potential strategies for addressing inaccuracies in risk perceptions.

What proportion of paediatric specialist referrals originates from general practitioners?

AIM: To determine (i) the proportion of different referral sources for new referrals to paediatric specialist outpatient clinics and (ii) any association of referral source with utilisation of additional health services. METHODS: Survey of parents presenting with their child at five paediatric specialist outpatient clinics at two Melbourne public hospitals. RESULTS: Just over half (52%) of the respondents were referred by a general practitioner (GP). The remainder were referred by a paediatrician (27%) at hospital discharge (16%) or from the ED (6%). Most respondents (71%) reported that their child also has a referral to see another specialist for the same health concern but had not yet had the consultation; 44% had consulted another doctor for the same health concern between receiving the referral and the appointment. Paediatrician referrals were more likely to see another specialist for the same health concern compared to other referral sources (P = 0.032). CONCLUSION: Only half of the referrals of new patients to paediatric specialist outpatient clinics come from GPs. Future research should investigate whether multiple referral sources have a negative impact on the co-ordination and cost of paediatric health care.

Feasibility of Coping Effectiveness Training for Caregivers of Children with Autism Spectrum Disorder: a Genetic Counseling Intervention.

Caregivers of children with autism spectrum disorder (ASD) may find it difficult to feel a sense of control and to cope with the overall physical and emotional demands of caring for their child. While caregivers are able to successfully cope with a high level of stress, there are limits to their resources and abilities to cope over time. Genetic counselors working with affected families may be able to help parents more effectively manage stress related to the disorder. Few short-term interventions have been reported in genetic counseling yet implementation of evidence-based examples may be achievable. This study aimed to assess the feasibility of a coping effectiveness training (CET) intervention designed to enhance coping self-efficacy (CSE) among caregivers of children with ASD, with the eventual goal of translating this intervention into genetic counseling practice. A randomized treatment-control design was used to investigate the feasibility of an intervention using CET among caregivers of children with ASD. The primary outcome was the feasibility of the intervention; the secondary outcome was improvements in CSE in the intervention group as compared to the control group. Caregivers were recruited and randomized into the treatment (n=15) or control (n=13) groups. Of these, 22 completed the study (retention: 78.6%). The intervention was highly feasible; most caregivers found the CET helpful, practical, useful, and relatively easy to attend. The treatment group demonstrated significantly increased CSE from pre-intervention to post-intervention (p=0.02). Between group differences were not significant when comparing the pre-post changes. We provide preliminary evidence that CET may be beneficial to caregivers of children with ASD. The results of this feasibility study support development of a phase II study of this intervention in a larger cohort, aimed to be implemented into a genetic counseling setting.