Genetic Testing and Other Healthcare Use by Black and White Individuals in a Genomic Sequencing Study.

INTRODUCTION: Early adopters play a critical role in the diffusion of medical innovations by spreading awareness, increasing acceptability, and driving demand. Understanding the role of race in the context of other characteristics of potential early adopters can shed light on disparities seen in the early implementation of genomic medicine. We aimed to understand the association between self-identified race and individual experience with genetic testing outside of the research context. METHODS: We assessed factors associated with the odds of having ever received genetic testing prior to enrollment in a genomic sequencing study among 674 self-identified white and 407 self-identified African, African American, or Afro-Caribbean ("Black") individuals. RESULTS: Controlling for individual determinants of healthcare use (demographics, personality traits, knowledge and attitudes, and health status), identifying as Black was associated with lower odds of prior genetic testing (OR = 0.43, 95% CI [0.27-0.68], p < 0.001). In contrast, self-identified race was not associated with the use of non-genetic clinical screening tests (e.g., echocardiogram, colonoscopy). Black and white individuals were similar on self-reported personality traits tied to early adoption but differed by sociodemographic and resource facilitators of early adoption. CONCLUSION: Persistent racial disparities among early adopters may represent especially-entrenched disparities in access to and knowledge of genomic technologies in clinical settings.

Elective genomic testing: Practice resource of the National Society of Genetic Counselors.

Genetic counseling for patients who are pursuing genetic testing in the absence of a medical indication, referred to as elective genomic testing (EGT), is becoming more common. This type of testing has the potential to detect genetic conditions before there is a significant health impact permitting earlier management and/or treatment. Pre- and post-test counseling for EGT is similar to indication-based genetic testing. Both require a complete family and medical history when ordering a test or interpreting a result. However, EGT counseling has some special considerations including greater uncertainties around penetrance and clinical utility and a lack of published guidelines. While certain considerations in the selection of a high-quality genetic testing laboratory are universal, there are some considerations that are unique to the selection of a laboratory performing EGT. This practice resource intends to provide guidance for genetic counselors and other healthcare providers caring for adults seeking pre- or post-test counseling for EGT. Genetic counselors and other genetics trained healthcare providers are the ideal medical professionals to supply accurate information to individuals seeking counseling about EGT enabling them to make informed decisions about testing and follow-up.

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.

Future-oriented Emotions and Decisions to Receive Genomic Testing Results Among U.S. Adults of African Ancestry.

BACKGROUND: Future-oriented emotions are associated with consequential health decision-making, including genomic testing decisions. However, little is known about the relative role of various future-oriented emotions in such decisions. Moreover, most research on predictors of decision making regarding genomic testing is conducted with white participants. PURPOSE: This study examined the role of future-oriented emotions in decisions to receive genomic testing results in U.S. individuals of African descent. METHODS: We analyzed cross-sectional survey data from a genomic sequencing cohort (N = 408). All participants identified as African, African-American, or Afro-Caribbean (Mage = 56.3, 74.7% female). Participants completed measures assessing anticipatory affect (worry about genetic testing results), anticipated distress (feeling devastated if genetic testing showed an increased risk for fatal disease), and anticipated regret (regretting a decision not to learn results). Outcomes were intentions for learning actionable, nonactionable, and carrier results. RESULTS: Anticipated regret was robustly positively associated with intentions to receive actionable (b = 0.28, p < .001), nonactionable (b = 0.39, p < .001), and carrier (b = 0.30, p < .001) results. Anticipated distress was negatively associated with intentions to receive nonactionable results only (b = -0.16, p < .01). Anticipatory negative affect (worry) was not associated with intentions. At higher levels of anticipated regret, anticipated distress was less strongly associated with intentions to receive nonactionable results (b = 0.14, p = .02). CONCLUSIONS: Our results highlight the role of future-oriented emotions in genomic testing among participants who are typically underrepresented in genomic testing studies and behavioral medicine broadly. Future work should examine whether interventions targeting future-oriented emotions such as anticipated regret may have clinically meaningful effects in genetic counseling in similar cohorts.

Future-oriented emotions (emotions directed toward a future outcome, such as worrying about a future outcome, or expecting to feel distress or regret if a particular outcome occurs) are important predictors of health decisions, including decisions to seek and receive genomic testing results. Understanding how such factors relate to decisions to receive genetic testing results is particularly important in medically-underserved groups such as individuals of African ancestry, who are underrepresented in genomics and behavioral science research. We analyzed survey responses from a genomic sequencing cohort where all 408 participants identified as African, African-American, or Afro-Caribbean, and were asked about their level of worry, anticipated distress, and anticipated regret about results, plus their interest in receiving three types of genomic testing results from the study. We found that participants who expected that they would regret their decision to not learn the results had stronger intentions to receive all three types of results; those who expected to feel distressed by a genetic testing result that showed an increased risk for a fatal disease were less interested in nonactionable genetic testing results specifically. Our results highlight the differing roles of specific types of future-oriented emotions in genomic testing decisions, among participants who are typically underrepresented in this type of research.

The role of future-oriented affect in engagement with genomic testing results.

Future-oriented emotions such as anticipatory affect (i.e., current affect experienced regarding a potential future outcome) and anticipated affect (i.e., expectations about potential future affect), are uniquely associated with health decision-making (e.g., electing to receive results of genomic testing). This study investigated the degree to which negative anticipated and anticipatory emotions predict health decision making over time, and whether such emotions predict social, emotional, and behavioral responses to anticipated information (e.g., genomic testing results). 461 participants (M age = 63.9, SD = 5.61, 46% female) in a genomic sequencing cohort who elected to receive genomic sequencing (carrier) results were included in the current study. Anticipated and anticipatory affect about sequencing results were assessed at baseline. Psychological and behavioral responses to sequencing results, including participants' reported anxiety, decisional conflict, and distress about sequencing results, whether they shared results with family members, and their intentions to continue learning results in the future, were collected immediately, one month, and/or six months after receiving results. More negative anticipated and anticipatory affect at baseline was significantly and independently associated with lower intentions to continue learning results in the future, as well as higher levels of anxiety and uncertainty at multiple time points after receiving results. Anticipated negative affect was also associated with greater decisional conflict, and anticipatory negative affect was also associated with greater distress after receiving results. Future-oriented emotions may play an important role in decisions that unfold over time, with implications for genomic testing, behavioral medicine, and health decision-making broadly.

The ACMG SF v3.0 gene list increases returnable variant detection by 22% when compared with v2.0 in the ClinSeq cohort.

PURPOSE: The American College of Medical Genetics and Genomics (ACMG) recommends the return of pathogenic and likely pathogenic (P/LP) secondary findings from exome and genome sequencing. The latest version (ACMG secondary finding [SF] v3.0) includes 14 additional genes. We interrogated the ClinSeq cohort for variants in these genes to determine the additional yield in unselected individuals. METHODS: Exome data from 1473 individuals (60% White, 34% African American or Black, 6% other) were analyzed. We restricted our analyses to coding variants; +1,+2,-1, and -2 splice site variants; and the pathogenic GAA variant, NM_000152.5:c.-32-13T>G. Variants were assessed with slightly modified ACMG/Association of Molecular Pathology guidelines. RESULTS: A total of 25 P/LP variants were identified. In total, 7 individuals had P/LP variants in genes recommended for return of heterozygous variants, namely HNF1A (1), PALB2 (3), TMEM127 (1), and TTN (2). In total, 4 individuals had a homozygous variant in a gene recommended for biallelic variant return, namely HFE, NM_000410.3(HFE):c.845G>A p.Cys282Tyr. A total of 17 P/LP variants were identified in the heterozygous state in genes recommended only for biallelic variant reporting and were not returned. The frequency of returnable P/LP variants did not significantly differ by race. CONCLUSION: Using the ACMG SF v3.0, the returnable P/LP variant frequency increased in the ClinSeq cohort by 22%, from 3.4% (n = 50, ACMG SF v2.0) to 4.1% (n = 61, ACMG SF v3.0).

Examining access to care in clinical genomic research and medicine: Experiences from the CSER Consortium.

INTRODUCTION: Ensuring equitable access to health care is a widely agreed-upon goal in medicine, yet access to care is a multidimensional concept that is difficult to measure. Although frameworks exist to evaluate access to care generally, the concept of "access to genomic medicine" is largely unexplored and a clear framework for studying and addressing major dimensions is lacking. METHODS: Comprised of seven clinical genomic research projects, the Clinical Sequencing Evidence-Generating Research consortium (CSER) presented opportunities to examine access to genomic medicine across diverse contexts. CSER emphasized engaging historically underrepresented and/or underserved populations. We used descriptive analysis of CSER participant survey data and qualitative case studies to explore anticipated and encountered access barriers and interventions to address them. RESULTS: CSER's enrolled population was largely lower income and racially and ethnically diverse, with many Spanish-preferring individuals. In surveys, less than a fifth (18.7%) of participants reported experiencing barriers to care. However, CSER project case studies revealed a more nuanced picture that highlighted the blurred boundary between access to genomic research and clinical care. Drawing on insights from CSER, we build on an existing framework to characterize the concept and dimensions of access to genomic medicine along with associated measures and improvement strategies. CONCLUSIONS: Our findings support adopting a broad conceptualization of access to care encompassing multiple dimensions, using mixed methods to study access issues, and investing in innovative improvement strategies. This conceptualization may inform clinical translation of other cutting-edge technologies and contribute to the promotion of equitable, effective, and efficient access to genomic medicine.

A systematic literature review of disclosure practices and reported outcomes for medically actionable genomic secondary findings.

PURPOSE: Secondary findings (SFs) are present in 1-4% of individuals undergoing genome/exome sequencing. A review of how SFs are disclosed and what outcomes result from their receipt is urgent and timely. METHODS: We conducted a systematic literature review of SF disclosure practices and outcomes after receipt including cascade testing, family and provider communication, and health-care actions. Of the 1,184 nonduplicate records screened we summarize findings from 27 included research articles describing SF disclosure practices, outcomes after receipt, or both. RESULTS: The included articles reported 709 unique SF index recipients/families. Referrals and/or recommendations were provided 647 SF recipients and outcome data were available for 236. At least one recommended evaluation was reported for 146 SF recipients; 16 reports of treatment or prophylactic surgery were identified. We found substantial variations in how the constructs of interest were defined and described. CONCLUSION: Variation in how SF disclosure and outcomes were described limited our ability to compare findings. We conclude the literature provided limited insight into how the American College of Medical Genetics and Genomics (ACMG) guidelines have been translated into precision health outcomes for SF recipients. Robust studies of SF recipients are needed and should be prioritized for future research.

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.

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.

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).

Adaptation of the working alliance inventory for the assessment of the therapeutic alliance in genetic counseling.

The concept of therapeutic alliance is central to genetic counseling as the mechanism through which the outcomes of empowerment and effective coping are likely to be achieved. To date, there have been no published systematic assessments of the therapeutic relationship in genetic counseling. We adapted a previously validated measure of the therapeutic alliance to genetic counseling and assessed its reliability and validity. Participants were enrolled in a clinical genomic study where they were randomized to receive education about carrier results via a Web platform or via a genetic counselor and then further randomized to receive genetic counseling (without additional education) or not. We rated the therapeutic alliance from audio recordings of 120 genetic counseling sessions. We modified the observer version of the Working Alliance Inventory (WAI-O), initially designed to assess therapeutic relationships in psychotherapy. We examined internal consistency reliability by calculating Cronbach's alpha and inter-rater reliability through both percent agreement and Gwet's alternative agreement coefficient (AC). Regression analyses were used to evaluate the relationship of WAI-O scores with session length and with the designation of the session as one in which prior education was delivered by the genetic counselor or not. The adapted scale had high-reliability characteristics with agreement of 88%-93%, Gwet's AC of 0.84-0.90, and Cronbach's alpha of 0.89-0.93 for the three WAI-O subscales (bonds, goals, and tasks). Although there was no difference in alliance based on whether prior education was provided by the genetic counselor, the total WAI-O score significantly increased with increasing session length (beta =0.667, p<.001), providing preliminary evidence of construct validity. The WAI-O that we have adapted can be used reliably with two independent raters to assess the therapeutic alliance in studies of genetic counseling. The initial evidence for construct validity is promising and should be reassessed in future genetic counseling studies using the WAI-O.

An open-source python library for detection of known and novel Kell, Duffy and Kidd variants from exome sequencing.

BACKGROUND AND OBJECTIVES: Next generation sequencing (NGS) has promising applications in transfusion medicine. Exome sequencing (ES) is increasingly used in the clinical setting, and blood group interpretation is an additional value that could be extracted from existing data sets. We provide the first release of an open-source software tailored for this purpose and describe its validation with three blood group systems. MATERIALS AND METHODS: The DTM-Tools algorithm was designed and used to analyse 1018 ES NGS files from the ClinSeq® cohort. Predictions were correlated with serology for 5 antigens in a subset of 108 blood samples. Discrepancies were investigated with alternative phenotyping and genotyping methods, including a long-read NGS platform. RESULTS: Of 116 genomic variants queried, those corresponding to 18 known KEL, FY and JK alleles were identified in this cohort. 596 additional exonic variants were identified KEL, ACKR1 and SLC14A1, including 58 predicted frameshifts. Software predictions were validated by serology in 108 participants; one case in the FY blood group and three cases in the JK blood group were discrepant. Investigation revealed that these discrepancies resulted from (1) clerical error, (2) serologic failure to detect weak antigenic expression and (3) a frameshift variant absent in blood group databases. CONCLUSION: DTM-Tools can be employed for rapid Kell, Duffy and Kidd blood group antigen prediction from existing ES data sets; for discrepancies detected in the validation data set, software predictions proved accurate. DTM-Tools is open-source and in continuous development.

Increased Burden of Rare Sequence Variants in GnRH-Associated Genes in Women With Hypothalamic Amenorrhea.

CONTEXT: Functional hypothalamic amenorrhea (HA) is a common, acquired form of hypogonadotropic hypogonadism that occurs in the setting of energy deficits and/or stress. Variability in individual susceptibility to these stressors, HA heritability, and previous identification of several rare sequence variants (RSVs) in genes associated with the rare disorder, isolated hypogonadotropic hypogonadism (IHH), in individuals with HA suggest a possible genetic contribution to HA susceptibility. OBJECTIVE: We sought to determine whether the burden of RSVs in IHH-related genes is greater in women with HA than controls. DESIGN: We compared patients with HA to control women. SETTING: The study was conducted at secondary referral centers. PATIENTS AND OTHER PARTICIPANTS: Women with HA (n = 106) and control women (ClinSeq study; n = 468). INTERVENTIONS: We performed exome sequencing in all patients and controls. MAIN OUTCOME MEASURE(S): The frequency of RSVs in 53 IHH-associated genes was determined using rare variant burden and association tests. RESULTS: RSVs were overrepresented in women with HA compared with controls (P = .007). Seventy-eight heterozygous RSVs in 33 genes were identified in 58 women with HA (36.8% of alleles) compared to 255 RSVs in 41 genes among 200 control women (27.2%). CONCLUSIONS: Women with HA are enriched for RSVs in genes that cause IHH, suggesting that variation in genes associated with gonadotropin-releasing hormone neuronal ontogeny and function may be a major determinant of individual susceptibility to developing HA in the face of diet, exercise, and/or stress.

Roles of attitudes and injunctive norms in decisional conflict and disclosure following receipt of genome sequencing results.

RATIONALE: Individuals who choose to obtain genetic information may learn that their genetic profile confers health risks to themselves or offspring. Individuals may react more negatively to this information when personal attitudes, perceived norms, and/or the decision to receive results conflict with one another. OBJECTIVE: We predicted that holding more negative attitudes (personal evaluations) or injunctive norms (perceptions of others' approval) toward obtaining genetic test results would prospectively predict greater conflict about the decision to undergo sequencing and less disclosure of sequencing results to family members. We also expected attitudes and norms to interact, such that attitudes would be negatively associated with decisional conflict and positively associated with disclosure when injunctive norms were positive, but weakly associated with outcomes when injunctive norms were negative. METHOD: Participants (N=312) were enrolled in a genomic sequencing trial focused on identifying carrier genetic variants, reflecting a variant that might affect their biological children's or grandchildren's health. Participants reported attitudes and injunctive norms, underwent sequencing, and later received results indicating carrier status for at least one variant. Decisional conflict was assessed at immediate post-test, and 1- and 6-month follow-ups. Disclosure of results to children and siblings were assessed at 1 and 6 months. RESULTS: In structural equation models with covariates, attitudes were negatively associated with post-test and 1-month decisional conflict. Injunctive norms were negatively associated with decisional conflict at 1 and 6 months and positively associated with disclosure to children and siblings at 1 month. The significant attitudes by injunctive norms interaction predicting post-test decisional conflict supported lower decisional conflict when attitudes, norms, and the decision to receive results were all aligned. Exploratory analyses supported indirect effects of attitudes and norms on 6-month sibling disclosure via 1- month decisional conflict. CONCLUSION: Results support roles of psychosocial factors in decisional conflict and disclosure after receiving sequencing results.

Perceptions of uncertainties about carrier results identified by exome sequencing in a randomized controlled trial.

How individuals perceive uncertainties in sequencing results may affect their clinical utility. The purpose of this study was to explore perceptions of uncertainties in carrier results and how they relate to psychological well-being and health behavior. Post-reproductive adults (N = 462) were randomized to receive carrier results from sequencing through either a web platform or a genetic counselor. On average, participants received two results. Group differences in affective, evaluative, and clinical uncertainties were assessed from baseline to 1 and 6 months; associations with test-specific distress and communication of results were assessed at 6 months. Reductions in affective uncertainty (∆x̅ = 0.78, 95% CI: 0.53, 1.02) and evaluative uncertainty (∆x̅ = 0.69, 95% CI: 0.51, 0.87) followed receipt of results regardless of randomization arm at 1 month. Participants in the web platform arm reported greater clinical uncertainty than those in the genetic counselor arm at 1 and 6 months; this was corroborated by the 1,230 questions asked of the genetic counselor and residual questions reported by those randomized to the web platform. Evaluative uncertainty was associated with a lower likelihood of communicating results to health care providers. Clinical uncertainty was associated with a lower likelihood of communicating results to children. Learning one's carrier results may reduce perceptions of uncertainties, though web-based return may lead to less reduction in clinical uncertainty in the short term. These findings warrant reinforcement of clinical implications to minimize residual questions and promote appropriate health behavior (communicating results to at-risk relatives in the case of carrier results), especially when testing alternative delivery models.

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.

Using the diffusion of innovations model to guide participant engagement in the genomics era.

Exome and genome sequencing (EGS) are increasingly the genetic testing modalities of choice among researchers owing to their ready availability, low cost, and large data output. Recruitment of larger, more diverse cohorts into long-term studies with extensive data collection is fundamental to the success of EGS research and to the widespread benefit of genomic medicine to various populations. Effective engagement will be critical to meeting this demand. The Diffusion of Innovation (DOI) model provides a framework for how new technologies are adopted in communities, including antecedents of an individual's decision to adopt the technology, how the technology's attributes influence its acceptability, the predictors of sustained use of that technology, and its diffusion through society. We apply the DOI model to frame participant engagement in EGS research and to guide the proposal of potential strategies that aim to overcome forecasted challenges. Finally, we suggest a variety of ways genetic counselors can apply their skills and training to the development and implementation of these strategies.

Knowledge, motivations, expectations, and traits of an African, African-American, and Afro-Caribbean sequencing cohort and comparisons to the original ClinSeq® cohort.

PURPOSE: Racial minority populations are underrepresented in genomics research. This study enrolled African-descended individuals in a sequencing study and reported their characteristics. METHODS: We purposively recruited 467 individuals self-identified as African, African American, or Afro-Caribbean to the ClinSeq® study and surveyed them about knowledge, motivations, expectations, and traits. Summary statistics were calculated and compared with data from the study's original cohort, which was primarily White and self-referred. RESULTS: Recruitment took five years and 83% of enrollees completed the survey. Participants had modest knowledge about benefits and limitations of sequencing (x̅s = 5.1, ranges: 0-10), and less than the original cohort (x̅ = 7.5 and 7.7, respectively). Common motivations to enroll were learning information relevant to personal health (49%) or family members' health (33%), and most had realistic expectations of sequencing. Like the original cohort, they had high levels of optimism, openness, and resilience. CONCLUSION: Early adopters may have relatively consistent personality traits irrespective of majority/minority status and recruitment methods, but high levels of genomics knowledge are not universal. Research should determine whether recruitment and consent procedures provide adequate education to promote informed choices and realistic expectations, which are vital to ethical research and increasing genomics research participation in underrepresented communities.

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.