BACKGROUND

Rapid genome-wide sequencing (rGWS) is being increasingly used to aid in prognostication and decision-making for critically ill newborns and children. Although its feasibility in this fast-paced setting has been described, this new paradigm of inpatient genetic care raises new ethical challenges.

OBJECTIVE

A scoping review was performed to (1) identify salient ethical issues in this area of practice; and (2) bring attention to gaps and ethical tensions that warrant more deliberate exploration.

METHODS

Data sources, Ovid Medline and Cochrane Central Register of Controlled Trials, were searched up to November 2021. Articles included were those in English relating to rGWS deployed rapidly in a critical care setting. Publications were examined for ethical themes and were further characterized as including a superficial or in-depth discussion of that theme. New themes were inductively identified as they emerged.

RESULTS

Ninety-nine studies, published in 2012 or thereafter, met inclusion criteria. Themes identified elaborated upon established ethical principles related to beneficence and nonmaleficence (ie, clinical utility, medical uncertainty, impact on family, and data security) autonomy (ie, informed consent), and justice (ie, resource allocation and disability rights). Many themes were only narrowly discussed.

CONCLUSIONS

The application of rGWS in neonatal and pediatric acute care is inherently tied to ethically charged issues, some of which are reported here. Attention to the ethical costs and benefits of rGWS is not always discussed, with important gaps and unanswered questions that call for ongoing focus on these ethical considerations in this next application of acute care genomics.

Since first applied to NICUs 10 years ago,1  rapid genome-wide sequencing (rGWS), including whole exome and whole genome sequencing, has become part of the evaluation of critically ill newborns and children suspected of having genetic contributions to their presentation. These tests, which can return genomic results in hours to days rather than months for conventional genetic testing, represent a shift away from the long “diagnostic odysseys” that have traditionally been the norm with conventional genetic work-ups.2  With diagnostic information that can be delivered to care teams and families at the point of care, such that they may aid in prognostication and decision-making or allow for personalized care at earlier disease or life stages, a new paradigm of genetic care has emerged, and with this, new challenges.

The ethical issues associated with conventional genetic testing in the pediatric context, such as managing uncertain or secondary findings, and notions of medical benefit and parental consent, have been discussed extensively and are well described.3  However, rGWS at a critical moment in care, and in a setting not historically staffed by genomic professionals, has prompted these ethical issues to resurface. The expanded offer of “hypothesis free” or untargeted testing in a phenotype that may not have fully declared itself or that may not have traditionally been flagged as genetic in nature (eg, neonatal encephalopathy or nonimmune fetal hydrops) pose challenges to result interpretation. Additionally, the high stakes emotionally charged environment of critical care and the potential timing of results at an early stage in life and potentially amid important care decisions add complexity. Given rGWS applications will expand, with a recent review calling for a new standard of care,2  our group embarked on a scoping review to capture the emerging ethical issues in this new application of genomic care. Some work in this area has already begun2,47 ; this review furthers this thinking by providing a descriptive overview of the ethical issues associated with rGWS in both the clinical and ethics literatures and, based on this, highlights gaps and challenges that warrant further discussion. As the application of rGWS in this setting is inherently tied to ethically charged clinical issues (eg, redirection of care), we hope this bringing together of ethics and clinical care can inform future research and practice.

A scoping review was performed to (1) identify salient ethical issues in the literature in this area of practice; and (2) bring attention to gaps and ethical tensions that warrant more deliberate exploration. Our scoping review was guided by the question “What are the ethical issues that arise in practice when whole exome or whole genome sequencing is applied rapidly or in critical care settings”?

A comprehensive search strategy was developed with a reference librarian at our pediatric hospital on the topic of rGWS in pediatric or neonatal intensive care units. Example search terms included: neonatal or pediatric ICUs and rapid whole exome or genome sequencing (Full search terms available in Supplemental A). An initial search was conducted in February 2020 via Ovid Medline and the Cochrane Central Register of Controlled Trials on the topic of rGWS in pediatric or neonatal intensive care units. Because of an evolving evidence base over the course of this work, an updated search in November 2021 was conducted. Study procedures followed Arksey and O’Malley’s framework for conducting scoping reviews and the Preferred Reporting Items for Systematic Revies and Meta-Analyses (PRISMA) extension for scoping reviews (PRISMA-ScR) guidelines.

Citations were imported into the Covidence software, where duplicate studies were removed. The title and abstracts of the remaining articles were screened according to the following inclusion criteria by 2 authors, with no significant discrepancies: (1) English language and (2) study related to diagnostic genetic testing deployed rapidly in a critical care setting. Articles were excluded if they discussed genetic testing of bacterial or viral genomes. Importantly, all study types were included in the event a salient ethical issue emerged, realizing this may not have been the paper’s primary purpose. Articles were included whether they explicitly mentioned ethical issues, to gauge the extent to which these tensions surfaced and to consider both clinical and ethics dialogues in one work. Any differences in eligibility were resolved by a third reviewer, when necessary. The PRISMA diagram is depicted in Fig 1.

Two authors (A.S., and D.C.) extracted the following information from each article: authors, year of publication, country of corresponding author, type of journal (ie, primary readership is: genetics professionals, pediatricians, general medicine, or ethics and law), type of study, aims of study (ie, if primary objective was to explore ethical issues or not), outcomes measured, and results. Publications were then examined for ethical themes, based on a coding framework informed by Beauchamp and Childress' Principles of Biomedical Ethics.8  In the early stages of data collection, the group met regularly to discuss emerging patterns and achieve consensus on the following framework and definitions, hoping to use a vernacular familiar to practicing clinicians: (1) beneficence and nonmaleficence (defined as the moral obligation “to act for the benefit of others” and “to abstain from causing harm to others”, respectfully8 ); (2) respect for autonomy (defined as the requirement that “autonomous actions not be subjected to controlling constraints of others” and “respectful treatment in disclosing information and actions that foster autonomous decision making.”8 ); and (3) justice (defined to include distributive justice [ie, the equitable distribution of benefits and burdens, fair opportunity, and unfair discrimination]). Content was then coded by 2 of 4 reviewers (J.A., L.C., A.S., and D.C.), who mapped whether these ethical issues were mentioned in a publication. Using an inductive approach,9  reviewers also identified additional themes as they emerged and met regularly to compare and collapse or expand similar themes. To capture the significance of a theme, articles were further characterized as including a superficial or in-depth discussion of that theme (defined as finding 1 supporting annotation or mentioning an ethical issue versus finding multiple supporting annotations and exploring the issue deeply). All discrepancies were resolved through group discussion. Gaps were discussed upon completion of coding by the coauthors, who collectively have background and expertise in bioethics, clinical genetics, genetic counseling, neonatology and health policy, and health services research. To enhance rigor throughout data collection and analysis, coauthors used reflexivity to attend to their own biases. The PRISMA-ScR checklist was used to guide the reporting of results.10 

Of 191 abstracts, 102 studies underwent full-text review by 2 independent reviewers. Three were excluded as they were deemed irrelevant, or did not meet inclusion criteria, resulting in 99 studies (Fig 1). All included studies were published in 2012 or after, with a plurality published in 2021 (n = 26). Fifty-one studies were American, with Australia (n = 13), China (n = 10), the United Kingdom (n = 7), and Canada (n = 6) having also published. A description of studies is depicted in Table 1. The salient themes that emerged and their frequencies are listed in Table 2 and Fig 2, respectively. Although there were 99 papers included in this work, exploring ethical issues was the central objective in 8 (8%),47,1114  with 25 others (25%) with in-depth ethical discussions that centered around 1 or more themes (eg, parental experiences).2,1540  Gaps and ethical tensions, the most prominent of which was that ethical issues were not always discussed, are depicted in Table 3 and explored in the discussion.

We identified 7 subthemes grouped under 3 general themes. Under beneficence and nonmaleficence, we identified subthemes of clinical utility, medical uncertainty and provider concerns, personal impact on parents and family, data security and privacy concerns. Under autonomy, we identified challenges of informed consent. Under justice, we identified subthemes of resource allocation and distributive justice, and discrimination and disability rights.

1. Beneficence and Nonmaleficence

Several subthemes related to balancing benefits and potential harms were identified.

1.1 Clinical Utility

Whereas the utility of a test is a common metric used in the scientific literature, it is also important from an ethical point of view. To assess the ethical justifiability of rGWS in the critical care of children, the harms of rGWS must be weighed against the benefits. Findings herein contribute to efforts in the field aimed toward characterizing the context-specific notion of benefit. Not surprisingly, a majority of papers (n = 88, 89%)1,2,47,1114,15,18,2229, 32, 33, 36101 & 103  and all 8 papers where exploring ethical issues was a central objective discussed the benefit of genomic sequencing in critically ill children, as it pertains to achieving a diagnosis. This was particularly true where rGWS was a first-line test initiated early in the admission process,67  with turnaround times between 24 hours93  and within a few weeks. Whereas there were heterogeneous designs and inclusion criteria, diagnostic yield in some cohorts reached 72%83  and rGWS was perceived to be useful by both clinicians and parents.23,53,69  In some work, results informed acute management in up to 95% of children who received a diagnosis.74  This was caused by the initiation of targeted investigations or consultations, or revision of the care plan by discontinuation, deferral, or avoidance of procedures or medication expected to be ineffective or potentially harmful, based on the diagnosis. Rapid diagnosis also enabled access to precision treatments69  and to investigational drugs via enrollment into clinical trials at a potentially more therapeutically responsive stage in the disease course.59  Benefit was also described with nondiagnostic results, especially with regards to rendering a genetic etiology less likely, and offering support for other decisions to move forward, such as transplantation.29,69,85 

Improved prognostication was cited as another benefit of rGWS in some work, enabling earlier guidance for families in establishing goals of care, instituting supportive treatments, or in the redirection of care to minimize suffering in disorders associated with unfavorable prognoses.62,75  Knowledge of a disorder’s anticipated natural history also allowed for planning long-term management by defining surveillance protocols, looking for comorbidities, and enabling early access to therapies for children at high risk of developmental disorders, potentially improving quality of life later on.60 

Rapid testing also enabled genetic counseling and pregnancy planning for parents based on recurrence risk.1,18,24,43,44,50,59,63,71,82,93,94,98  Clinical utility for others through the identification of at-risk relatives for both primary and secondary findings was also described.34,44,70  A further extension of utility to other families, and to the medical field in general, was discussed by expanding the understanding of a known condition or delineating a novel one when rGWS is performed.36  The opportunity for dynamic reinterrogation of genomic data as the clinical course evolves or as the genetic knowledge base expands was discussed as allowing for future utility.65,66 

1.2 Medical Uncertainty and Provider Concerns

Concerns related to the medical uncertainty associated with genetic information was another subtheme related to beneficence and nonmaleficence, mentioned in 37 papers (37%)2,46,1113,14, 15,17,18,2225,29,30,32,33,34,37,38,40,46,47,50,52,59,61,75, 79,86,89,94,95,97,103  including 7 of 8 ethics papers.46,1114  Although testing may have helped some providers feel at ease with clinical decisions, provider concerns on how to interpret variants of uncertain significance and how to apply these to clinical decisions were also described.4,13,30,37,38  Gubbels noted related challenges in the neonatal context,62  as even when there was certainty about a diagnosis, there may have been uncertainty about its natural history or clinical spectrum because of the rarity of the syndrome or an evolving knowledge base. It was felt the children undergoing rGWS may also represent some of the youngest described with a particular condition, creating additional uncertainty both in terms of prognosis but also in how to leverage this information to guide acute decisions. More fundamental questions of to whom testing should be offered and what (research or clinical) results to return were also raised.5,34,84,85,102 

A call to improve genomic literacy for providers, either in the form of capacity building of nongenetics professionals, or in mobilizing more genetic professionals to critical care was discussed.11,13,15,29,30,38  This was thought to be especially useful for posttest interpretation, as inference of findings on disease course can be unclear and potentially confusing.4  Additionally, the goals of testing, even between genetics and nongenetics care providers, may differ. These groups may operate with different decision-making paradigms, creating additional tensions.15,21,22  Appropriate and timely test selection may warrant new models of care, clearer delineation of clinical roles, and changes in laboratory infrastructure to reflect new workflows.15 

The potential for negative impacts on parental bonding,6,29  parental psychosocial distress,25,31,40  and privacy (discussed with respect to impact on parents) were also a concern for providers.4,33,37  Concerns related to the tension between parents’ right to know and a child’s right to an open future were also noted.33,37,38,75  Finally, as mentioned under autonomy, providers were concerned about the ability to obtain truly informed consent in acute care settings.6,29 

1.3 Personal Impact on Parents and Family

The psychosocial impacts of rGWS on families were mentioned in 39 studies (39%),2,47,11,1520,2229,3133,35,38,44,45,47,49,52, 56,61,75,76,79,89,94,96,99  in 5 of 8 ethics papers,47,11  and exploring these was the central objective of 7 studies.16,18,2325,27,29  These studies identified test-related concerns that parallel those of providers including: themes related to uncertainty, particularly if diagnoses turned out to be wrong25,29 ; concerns about the interaction between rGWS and discriminatory attitudes toward disability, discussed later33 ; and psychological distress from the stressful setting of the ICU.30  Hill and others29  also mentioned that an offer of genetic testing itself may create anxiety and/or cause parents to realize the seriousness of their child’s illness, while inflicting an additional emotional burden of worrying about results.25,29  Whereas parents who received a life-limiting diagnosis for their child in these studies understandably experienced sadness and grief, some literature suggested that even so, they expressed favorable views of testing, often centering on the hope for an answer that could improve their child’s health.23,24,29  Importantly, some parents who received nondiagnostic or inconclusive results described positive impacts.18  At the same time, in 1 study, whereas more than half of parents had no decisional regret, 26% experienced mild and 15% experienced moderate to high decisional regret whether the test was diagnostic or their child survived.18  Some parents experienced reduced uncertainty and closure from obtaining an answer, as well as reassurance regarding decisions about their child’s goals of care.23,25,29  Still, others faced new challenges navigating limited resources when a rare condition was diagnosed that did not have a clear medical home.25,28,96 

There were other notable psychosocial effects described. One study found that 15% of parents refused testing of their child for fear of learning distressing information at an already stressful time.27,29,37  With regards to receiving a genetic diagnosis rapidly, some work discussed that the limited contact with a newborn, the early stage in life at which a diagnosis is established, and the absence of the typical waiting period for a genetic diagnosis may disrupt family-dynamics and, in particular, the parent-child bond.6,16,25,28,32,37,76  At least 1 study discussed parental sadness that such testing was not offered in-utero,18  with another mentioning adoption as an outcome after rGWS results.6 

1.4 Data Security and Privacy Concerns

Ten studies (10%)4,11,15,19,25,28,33,37,40,41  addressed concerns around the privacy and security of genetic information discovered when pursuing rGWS. Two of the ethics-focused articles discussed this.4,11  Clinicians also expressed concern over potential misuse of this information by third parties such as insurance companies.37  Some papers brought up the familial nature of genetic information and that information discovered in a child may also be important for relatives.4  It is worth noting that decisions to return secondary findings for both the child and/or parents may have been handled differently depending on study design, which may have made these concerns more or less apparent.74  Whether parents were knowingly consenting to future uses or reanalysis of genetic information was also unclear in some work, although parents did list altruistic reasons and furthering research as motivations for agreeing to pursue rGWS.29  These privacy issues are not new, but the nature of the consent process, described next, and the young age at which many of these children are undergoing testing, may highlight these challenges.

2. Autonomy

2.1 Challenges Related to Informed Consent

Discussions related to autonomy and informed consent were present in 21 papers (21%)47,11,18,19,2225,2730,3335,37,38,85  and 5 of 8 ethics papers.47,11  These included typical challenges of nonrapid genetic testing, such as decisions to return of secondary findings, which have been previously published and discussed.34,40  A number of papers highlighted how having a critically ill child complicates decision-making for parents and families. It was proposed that the vulnerability and stress experienced by parents because of their child’s admission, or the rushed nature of the decisions at hand, may render them less able to process complex medical information, threatening their ability to provide meaningful consent to rGWS.6,28,29  In some cases, the offer of the test may also present a sense of inflicted ought from parents.25 

Diamonstein30  identified 4 factors influencing parent consent to rGWS in the ICU context: (1) parents’ emotional state; (2) involvement of multiple health care providers; (3) environmental distractions; and (4) competing clinical priorities. According to Diamonstein, all these factors may conspire to undermine informed consent to rGWS in the ICU.

Understanding motivations for declining testing, or how to resolve potentially different views between parents and the healthcare team or between healthcare teams, on the value of testing were also flagged.60  Because of the complexity of both the environment and the information, it was felt that rGWS highlights the need for genetics expertise and the provision of thorough, yet potentially reimagined, pre and post-test counseling.4,13,28,30,37,38,62  At the same time, the idea that such a test could potentially occur even in the absence of consent was raised, particularly if highly relevant to decision-making or care and in a child’s best interest,4  bringing in new team tensions17  and child protection concerns.71 

3. Justice

3.1 Resource Allocation

Justice related themes were identified regarding the fair allocation of resources and distributive justice, or fairness in access to rGWS. Fifty-three studies (54%)1,2,4,6,11,12,14,19,21,22,25,28,29,32,36,3845,47, 4952,56,58,6063,6871,73,8386,89,90,9297,99,102  and 5 of 8 ethics studies4,6,11,12,14  included this theme, most centering on rGWS as a faster and potentially less expensive test in the long run,50  notwithstanding potential up-front technological and personnel costs.13,29  Others focused on cost savings caused by shortened length of stay and net healthcare savings in children undergoing rGWS, which may have been because of earlier access to care, avoiding unnecessary treatments and procedures, or in the decision to redirect care.47,57,85,93,97  Though the majority of papers that reflected on this theme described a reduction in expenses, several papers demonstrated that costs may actually increase using rGWS in a NICU setting given higher costs of admission, associated investigations and testing,84  and downstream costs associated with rGWS results.60  Some studies that recommended implementation of rGWS consider cost-saving alternatives, including clinical genetics consults or smaller gene panels.44,90  Concerns related to distributive justice and equitable access to testing were also mentioned, raising another potential liability of expensive testing, both between inpatients and when considering outpatient access.4,6,7,21,76 

3.2 Discrimination and Disability Rights

Nine studies (9%) discussed issues of disability-based discrimination as a consequence of rGWS,4,6,7,11,19,24,25,27,33  including 4 of 8 ethics pieces.4,6,7,11  A few identified concerns from parents and providers that rGWS may exacerbate discriminatory or ableist attitudes toward disability in end of life decision-making and encourage framing disability as an avoidable cost to the health care system.7,11,29,33,38  It was felt that implicit bias may also shape when rGWS is offered, the way in which pre and posttest counseling are administered, and what clinical decisions are offered or made.11  These concerns are important in relation to well-known conditions, but may be particularly pressing in relation to emerging or less well-understood conditions, as decisions to withdraw life-sustaining treatments may preclude the development of medical knowledge about them.11  Historically, this pattern has played out repeatedly, creating a self-fulfilling prophecy for children with genetic conditions who were not offered therapeutic opportunities.6,11 

In this scoping review, we identified 7 subthemes grouped under 3 general principles of biomedical ethics. These help to better characterize the nuanced benefits and burdens of rGWS in pediatric care and acknowledge the complex needs of critically unwell patients and their families. That being said, our findings also highlight what is missing, or only minimally present, in the clinical literature: serious attention to the ethical costs and benefits of rGWS in this context.

Many of the key themes we identified were discussed only minimally (eg, discrimination and disability rights) or may have been reported with respect to singular cases with unique contexts (eg, redirection of care). Indeed, clinical utility was the primary ethical theme in the majority of papers, though this often boiled down to discussions of feasibility only (eg, diagnostic yield, turnaround time, and length of stay). Insofar as bona fide assessments of clinical utility involve weighing all the harms and the benefits of an intervention, this minimal discussion of a subset of potential harms warrants further reflection and speaks to an important gap in how the adoption of new technologies is discussed and evaluated.

Second, we wonder whether the tensions identified reflect the reality of an interdisciplinary endeavor that is still in its infancy. Anxious parents may look for hope, guidance, and space to make decisions as they navigate their child’s journey through the healthcare system. Intensivists skilled in acute care, clinical decision-making, and navigating difficult discussions with patients and families now have a new tool to integrate into acute care decisions. Clinical geneticists and genetic counsellors who have comfort and familiarity with variable phenotypes, the uncertain nature of genetic “prognostication,” and the psychosocial dynamics inherent in searching for and adapting to a genetic diagnosis need to acclimatize to this critical care setting. In the past, they and their laboratory colleagues may have had limited roles there because of, in part, conventional genetic testing options and a different genetics knowledge base. We may take lessons from other issues in critical care and outside of it: the introduction of MRIs, for example, highlighted similar tensions between prognostication and uncertainty, and potential tensions between teams and families in care decisions.104  Team culture and communication, described in other work, also highlights the differing boundaries and skillsets intensivists and consulting teams may bring to patient care.105  These complexities of interdisciplinary care and ensuring continuity of care represent ethical challenges in their own right and suggest the need for novel team-based, family-centered approaches for joint decision-making and ongoing evaluation of the impact of the offer of rapid testing for care teams, patients, and families. Additional attention on how to reach all relevant stakeholders for meaningful dialogue, through publication or other means, is warranted.

Third, the rapidity of these tests, often offered in the first few hours or days of life underpins a few of the ethical themes described, yet gaps remain in our understanding of whether faster is always better. Whereas rapid genetic testing for certain indications (eg, trisomy 13 or 18) has been present for some time, what is new is the availability of rapid, broad-based testing for rare and/or recently described conditions in the newborn, coupled with expanding knowledge about the genetic basis of some presentations. Additionally, there is still a conventional (months) and rapid (days to weeks) option, and a deliberate decision needs to be made as to who may benefit from fast turnaround of results. A rapid result may be welcome after a long diagnostic odyssey or in cases where results guide management. Other times, turnaround time may still be “too slow” to make a meaningful difference (eg, in a clinically deteriorating child) or “too fast” (eg, if it interferes with bonding). That is, potential sources of harm extend beyond the diagnostic capabilities of the test to considerations of time and place for result delivery. Perhaps not unlike newborn screening programs, early, unsought genetic information may at times be harmful.106 

Fourth, and finally, whether and how a molecular diagnosis ought to shape clinical care decisions or whether parents or clinicians ought to wait for results at all also warrants further exploration. The heterogeneous patient population and the differing values that parents and clinical teams bring to these decisions are important to recognize and acknowledge. Transparency with parents during the consent process concerning the potential reasons motivating testing and what types of decisions and discussion this may drive is paramount. How to determine whether testing is truly in the best interests of a critically ill child will need to be explored. Decisions that may be inconsistent with one’s own values should be respected as long as they are consistent with the child’s best interests. At the same time, a careful balance between reliance but not overreliance on results which may be preliminary or uncertain is needed, with space maintained for clinical decisions to be made in the absence of genetic results, whether or not these are pursued.

It is clear that the offer of a test at a critical moment in care makes the application of rGWS different than conventional genetic care occurring in an outpatient setting. At the same time, it is difficult to separate issues related to rapid testing from the mere availability of genetic testing in critical care contexts, particularly if there are also cultural shifts in these contexts in the perceived value and importance of achieving a genetic diagnosis. Just as with any new technology, the offer or even the availability of this test may change patient-provider relationships, care decisions and pathways, and how teams interact, making this intervention and its effects complex to describe and measure. Definitions of rapid testing also vary widely, with potential overlap of issues relevant when undertaking any genetic test.

We acknowledge that our methods may underrepresent ethical issues encountered in the field, as the absence of ethical issues in the literature does not imply there were none encountered, particularly when describing the ethical issues was not the primary purpose of the papers reviewed. The 4 principles were chosen to operationalize ethics in a clinical vernacular, though we may have characterized more negative or problematic issues related to rGWS because of the valence of our themes. Nevertheless, we feel this work captures many of the important and emerging ethical issues in this critical application of genomic testing.

rGWS has made major strides in providing families with timely and precise diagnoses. rGWS at a critical moment in care also raises numerous ethical issues, some of which are identified here. Attention to the ethical costs and benefits of rGWS is not always discussed, with important gaps and unanswered questions related to the complexities of the interdisciplinary environment, clinical care decisions, and the genomic information on offer. As this testing becomes a standard of care, we encourage groups to reflect on their local practices and look more broadly at the themes identified herein, capturing, where possible, both the benefits and ethical tensions this technology elicits. In particular, the parent experience and broader social context of individuals with disabilities or medical complexity, the nuances of which will not necessarily be captured by cost-effectiveness analyses or measures of clinical utility, ought to receive attention. Developing best practices for crossdisciplinary collaboration, operationalizing informed consent practices, and identifying which infants and issues are best suited to rGWS are important next steps in building fair and transparent processes. They will require a careful balance of family preference, clinical need, and best interest of the critically unwell child. Just as importantly, rGWS will continue to evolve. We anticipate that there will be new applications of rGWS and, with this, issues that warrant similar ethical reflection. Acknowledging the complexity of genomic information, the evolving clinical relationships, our biases, and the limitations of our technology will be just as important in guiding decisions and best practices as we move forward.

FUNDING: No external funding.

CONFLICT OF INTEREST DISCLOSURES: The authors have no conflicts of interest relevant to this article to disclose.

Drs Chad and Anderson conceptualized the study and performed data curation; Ms Cagliero and Ms Szuto performed data curation; all authors formally analyzed this study, wrote the original and review drafts, and reviewed the final manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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