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Genetic researchers' selection of a database can have scientific, regulatory, and ethical implications. It is important to understand what is driving database selection such that database stewards can be responsive to user needs while balancing the interests of communities in equitably benefiting from advances.We conducted 23 semistructured interviews with US academic genetic researchers working with private, government, and collaboratory data stewards to explore factors that they consider when selecting a genetic database.Interviewees used existing databases to avoid burdens of primary data collection, which was described as expensive and time-consuming. They highlighted ease of access as the most important selection factor, integrating concepts of familiarity and efficiency. Data features, such as size and available phenotype, were also important. Demographic diversity was not originally cited by any interviewee as a pivotal factor; when probed, most stated that the option to consider diversity in database selection was limited. Database features, including integrity, harmonization, and storage were also described as key components of efficient use.There is a growing market and competition between genetic data stewards. Data need to be accessible, harmonized, and administratively supported for their existence to be translated into use and, in turn, result in scientific advancements across diverse communities.

PURPOSE The use of genomic sequencing (GS) in military settings poses unique considerations, including the potential for GS to impact service members' careers. The MilSeq Project investigated the use of GS in clinical care of active duty Airmen in the United States Air Force (USAF). METHODS We assessed perceived risks, benefits, and attitudes toward use of GS in the USAF among patient participants (n = 93) and health-care provider participants (HCPs) (n = 12) prior to receiving or disclosing GS results. RESULTS Participants agreed that there are health benefits associated with GS (90% patients, 75% HCPs), though more HCPs (75%) than patients (40%) agreed that there are risks (p = 0.048). The majority of both groups (67% HCPs, 77% patients) agreed that they trust the USAF with genetic information, but far fewer agreed that genetic information should be used to make decisions about deployment (5% patients, 17% HCPs) or duty assignments (3% patients, 17% HCPs). Despite their hesitancy, patients were supportive of the USAF testing for nondisease traits that could impact their duty performance. Eighty-seven percent of patients did not think their GS results would influence their career. CONCLUSION Results suggest favorable attitudes toward the use of GS in the USAF when not used for deployment or assignment decisions.

Most professional guidelines recommend against genetic screening for adult-onset only conditions until adulthood, yet others argue there may be benefit to disclosing such results. We explored parents' decision-making on this issue in the BabySeq Project, a clinical trial of newborn genomic sequencing.We conducted interviews with parents (n=24) who were given the option to receive actionable adult-onset only results for their children. Interviews explored parents' motivations to receive and reasons to decline adult-onset only genetic disease risk information, their decision-making process, and their suggestions for supporting parents in making this decision.Parents noted several motivations to receive and reasons to decline adult-onset only results. Most commonly, parents cited early intervention/surveillance (n=11), implications for family heath (n=7), and the ability to prepare (n=6) as motivations to receive these results. The most common reasons to decline were protection of the child's future autonomy (n=4), negative impact on parenting (n=3), and anxiety about future disease (n=3). Parents identified a number of ways to support parents in making this decision.Results demonstrate considerations to better support parental decision-making that aligns with their values when offering adult-onset only genetic information as it is more commonly integrated into pediatric clinical care.

In recent years, third-party genetic interpretation services have emerged to help individuals understand their raw genetic data obtained from researchers, clinicians, and direct-to-consumer genetic testing companies. The objectives of these services vary but include matching users to genetic relatives, selling customized diet and fitness plans, and providing health risk assessments. As these services proliferate, concerns are being raised about their accuracy, safety, and privacy practices. Thus far, US regulatory agencies have not taken an official position with respect to third-party genetic interpretation services, which has caused uncertainty regarding whether and how they might be regulated. To clarify this area, we analyzed their potential oversight by four US agencies that generally have been active in the regulation of genetic testing services and information: the Centers for Medicare and Medicaid Services, the Food and Drug Administration, the Department of Health and Human Services’ Office of Civil Rights, and the Federal Trade Commission. We conclude that the scope of federal jurisdiction over third-party genetic interpretation services—while limited—could be appropriate at this time, subject to agency clarification and appropriate exercise of oversight.

PURPOSE: As exome and genome sequencing (ES, GS) enters the clinic, there is an urgent need to understand the psychological effects of test result disclosure. Through a Clinical Sequencing Exploratory Research (CSER), phase 1 (CSER1) consortium collaboration, we evaluated participants’ psychological outcomes across multiple clinical settings. METHODS: We conducted a random effects meta-analysis of state anxiety (Hospital Anxiety and Depression Scale (HADS)/ Generalized Anxiety Disorder-7 item), depressive symptoms (HADS/ Personal Health Questionnaire-9 item), and multi-dimensional impact (i.e., test-related distress, uncertainty and positive impact: modified Multidimensional Impact of Cancer Risk Assessment/ Feelings About Genomic Testing Results scale). RESULTS: Anxiety and depression did not increase significantly following test result disclosure. Meta-analyses examining mean differences from pre- to post-disclosure revealed an overall trend for a decrease in participants’ anxiety. We observed low levels of test-related distress and perceptions of uncertainty in some populations (e.g., pediatric patients) and a wide range of positive responses. CONCLUSION: Our findings across multiple clinical settings suggest no clinically significant psychological harms from the return of ES/GS results. Some populations may experience low levels of test-related distress or greater positive psychological effects. Future research should further investigate the reasons for test-related psychological response variation.

Purpose To examine patients’ experiences with clinical use of whole genome sequencing (WGS). Methods A randomized trial compared primary care and cardiology patients receiving WGS and family health history (FH) information or FH information alone. 202 patients were surveyed before (BL) and up to six months (6M) after disclosure of results. Results Patients (mean age = 55 years; 50% female; 81% college graduates) reported low levels of decisional regret (mean: 7.1/100) and high satisfaction with physicians’ disclosure of results (median = 29 / 30). Compared to the FH-only arm, patients receiving WGS results were more likely to report learning accurate disease risk information (OR = 7.45) and findings influential for medical treatment (OR = 2.39). Sessions where WGS results were disclosed took longer (30 vs. 15 minutes), particularly for primary care patients. Patients’ expected utility of sequencing at BL was higher than perceived utility at 6M in several domains, including impacting medical decision-making (87% vs. 54%) and influencing medication choice (73% vs. 32%). Conclusions Patients were satisfied with their physicians’ communication of WGS results and perceived them as medically useful. Discrepancies in expected versus perceived utility of WGS results suggest a need to temper patients’ expectations about its potential benefits.

On 13 December 2016, President Obama signed the 21(st) Century Cures Act (“the Act”) into law. Many of its provisions support the creation of an “Information Commons,” an ecosystem of separate but interconnected initiatives that facilitate open and responsible sharing of genomic and other data for research and clinical purposes. For example, the Act supports the National Institutes of Health in mandating data sharing, provides funding and guidance for the large national cohort program now known as All of Us, expresses congressional support for a global pediatric study network, and strengthens patient access to health information. The Act also addresses potential barriers to data sharing. For example, it makes the issuance of certificates of confidentiality automatic for federally-funded research involving “identifiable, sensitive” information and strengthens the associated protections. At the same time, the Act exacerbates or neglects several challenges, for example, increasing complexity by adding a new definition of “identifiable” and failing to address the financial sustainability of data sharing and the scope of commercialization. In sum, the Act is a positive step, yet there is still much work to be done before the goals of broad data sharing and utilization can be achieved.

Whether and how to return individual genetic results to study participants is among the most contentious policy issues in contemporary genomic research.We surveyed corresponding authors of genome-wide association studies, identified through the National Human Genome Research Institute's Catalog of Published Genome-Wide Association Studies, to describe the experiences and attitudes of these stakeholders.Of 357 corresponding authors, 200 (56%) responded. One hundred twenty-six (63%) had been responsible for primary data and sample collection, whereas 74 (37%) had performed secondary analyses. Only 7 (4%) had returned individual results within their index genome-wide association studies. Most (69%) believed that return of results to individual participants was warranted under at least some circumstances. Most respondents identified a desire to benefit participants' health (63%) and respect for participants' desire for information (57%) as major motivations for returning results. Most also identified uncertain clinical utility (76%), the possibility that participants will misunderstand results (74%), the potential for emotional harm (61%), the need to ensure access to trained clinicians (59%), and the potential for loss of confidentiality (51%) as major barriers to return of results.Investigators have limited experience returning individual results from genome-scale research, yet most are motivated to do so in at least some circumstances.

Purpose: Despite growing concerns toward maintaining participants' privacy, individual investigators collecting tissue and other biological specimens for genomic analysis are encouraged to obtain informed consent for broad data sharing. Our purpose was to assess the effect on research enrollment and data sharing decisions of three different consent types (traditional, binary, or tiered) with varying levels of control and choices regarding data sharing. Methods: A single-blinded, randomized controlled trial was conducted with 323 eligible adult participants being recruited into one of six genome studies at Baylor College of Medicine in Houston, Texas, between January 2008 and August 2009. Participants were randomly assigned to one of three experimental consent documents (traditional, n = 110; binary, n = 103; and tiered, n = 110). Debriefing in follow-up visits provided participants a detailed review of all consent types and the chance to change data sharing choices or decline genome study participation. Results: Before debriefing, 83.9% of participants chose public data release. After debriefing, 53.1% chose public data release, 33.1% chose restricted (controlled access database) release, and 13.7% opted out of data sharing. Only one participant declined genome study participation due to data sharing concerns. Conclusion: Our findings indicate that most participants are willing to publicly release their genomic data; however, a significant portion prefers restricted release. These results suggest discordance between existing data sharing policies and participants' judgments and desires.

Increasingly, genomic research is being conducted through large, multi-site consortia. For example, the eMERGE (Electronic Medical Records and Genomics) Consortium was funded by the National Human Genome Research Institute to evaluate the scientific feasibility and potential value of performing genome wide association studies (GWAS) using information from electronic medical records together with hundreds of thousands of single nucleotide polymorphisms (SNPs) from samples obtained in the course of existing cohort studies, biorepositories, or from residual tissue or blood samples. This experiment, if successful, will enable a vast amount of research, especially as more and more medical information is stored electronically and as the cost of genotyping and sequencing decreases. However, the ability to use existing clinical information and samples for GWAS, while exciting, raises a number of ethical, legal, social, and policy issues. Examples of some of the issues raised by this type of research include: What sort of consent, if any, is required for such research? When might it be necessary to obtain new consent for the use of previously collected samples? Recognizing the value and the cost of obtaining such rich clinical and genetic variation data, and the desirability of combining datasets to permit more robust analysis, the NIH has strongly encouraged GWAS funded by the NIH, including the eMERGE data, be placed in a central repository called the database of Genotypes and Phenotypes (dbGaP) for use by other qualified investigators.1 To what extent should patients and research participants be able to opt out of having their data shared with the broader research community through government-sponsored databases such as dbGaP? When diverse data sources are combined and then shared beyond the originating institutions, the abilities of investigators or biorepository managers to protect participants’ interests, including privacy, necessarily change. Given this shift, do the obligations of those who originally collected samples change, and if so, how? Should investigators’ obligations differ depending on whether data and samples come from patients seeking routine care or from participants in a preexisting research project? When, if ever, should research results, either aggregate or individual, be returned to participants? What about incidental findings? And what role should communities play in long-term oversight and governance of these projects? To address these, and related concerns, each eMERGE site was required to bring together genetic researchers and ELSI investigators to address the ethical and social challenges of such research. Building an ethics component into large scientific studies provides an opportunity for transdisciplinary ELSI (ethical, legal, and social implications) research that is immediately responsive to the emerging issues raised by scientific innovation, an approach that is becoming more common in genomics research.2-4 The eMERGE Consortium provides a particularly rich landscape in which to pursue such research. The five partner institutions are examining data from a variety of populations that differ in their demographic characteristics, the ways they were recruited, and in the depth and stability of their relationships with the particular research team and institution (Table 1). Each eMERGE site includes investigators who bring particular disciplinary perspectives and approaches to studying the implications of using information from electronic medical records for GWAS (Table 1). (Additional Information about each member site and its research can be found at www.gwas.net). Table 1 In order to maximize what can be learned from the diverse eMERGE research settings, ELSI investigators are not only conducting transdisciplinary research at their own institutions, but have also joined together in a Consent and Community Consultation (C&CC) Working Group to share strategies and results and to collaborate on ethical issues and policy related to the conduct of GWAS. To facilitate this work, a number of prominent investigators from non-eMERGE institutions were invited to join the C&CC Working Group. Their names and affiliations are listed at the end of this article. The larger group quickly organized a number of smaller groups to focus on key, cross-cutting topics. The current groups, their leadership, and their goals follow

Modern biobanking efforts consist of prospective collections of tissues linked to clinical data for patients who have given informed consent for the research use of their specimens and data, including their DNA. In such efforts, patient autonomy and privacy are well respected because of the prospective nature of the informed consent process. However, one of the richest sources of tissue for research continues to be the millions of archived samples collected by pathology departments during normal clinical care or for research purposes without specific consent for future research or genetic analysis. Because specific consent was not obtained a priori, issues related to individual privacy and autonomy are much more complicated. A framework for accessing these existing samples and related clinical data for research is presented. Archival tissues may be accessed only when there is a reasonable likelihood of generating beneficial and scientifically valid information. To minimize risks, databases containing information related to the tissue and to clinical data should be coded, no personally identifying phenotypic information should be included, and access should be restricted to bona fide researchers for legitimate research purposes. These precautions, if implemented appropriately, should ensure that the research use of archival tissue and data are no more than minimal risk. A waiver of the requirement for informed consent would then be justified if reconsent is shown to be impracticable. A waiver of consent should not be granted, however, if there is a significant risk to privacy, if the proposed research use is inconsistent with the original consent (where there is one), or if the potential harm from a privacy breach is considerable.

As clinical genetics evolves, and we embark down the path toward more personalized and effective health care, the amount, detail, and complexity of genetic/genomic test information within the electronic health record will increase. This information should be appropriately protected to secure the trust of patients and to support interoperable electronic health information exchange. This article discusses characteristics of genetic/genomic test information, including predictive capability, immutability, and uniqueness, which should be considered when developing policies about information protection. Issues related to "genetic exceptionalism"; i.e., whether genetic/genomic test information should be treated differently from other medical information for purposes of data access and permissible use, are also considered. These discussions can help guide policy that will facilitate the biological and clinical resource development to support the introduction of this information into health care.

Purpose: Current genomic research policy calls for public data release with specific consent for data sharing. Because most clinical investigators are not responsible for and do not anticipate data broadcast few include information about data sharing in their informed consent process. Model language is therefore urgently needed and should be responsive to research participants' attitudes and judgments. The purpose of this study was to describe research participants' attitudes and judgments about data release and their preferences for varying levels of control over decision-making. Methods: Focus group sessions with patients and controls from a genetic study of epilepsy. Results: Despite wide variation in judgments, there was general interest in receiving information and making decisions about data sharing. Participants preferred multiple data sharing options, but were more likely to consent to public data release when given fewer options. For existing samples most participants felt that genomic information should not be publicly released without explicit consent from research participants. Conclusions: Specific information about data sharing ought to be included in the consent process for all genetic research. These participants desire multiple data release options, but the effect, if any, on consent to public release deserves further investigation.

Return of individual research results (IRRs) to study participants has been, and continues to be, hotly debated. The role of biobanks in the return of research results had received little attention until the recent publication from Susan Wolf et al.,1 which presents a detailed discussion and 10 recommendations regarding the return of results from biobanks. The authors propose that if reidentification of an individual participant (whom they also call a “contributor”) is possible, the biobank, as the central hub in a biobank research system, should enable the system to (i) clarify the criteria for evaluating findings and develop a list of returnable findings; (ii) analyze a particular finding in relation to the aforementioned list/criteria; (iii) reidentify the individual participant/contributor; and (iv) recontact them to offer the finding. Wolf et al.1 propose that the biobank would bear the long-term responsibility for the return of incidental findings (IFs) and IRRs rather than the investigators themselves. These recommendations neither sufficiently reflect the wide variability in both the purpose and nature of biobanks nor do they take into account the associated costs to biobanks and the research system. Biobanks encompass disease-specific and healthy cohorts and range from small collections in individual laboratories to international collections involving many thousands of people.2

Genet Med (2013) 15, 565–574 doi:10.1038/gim.2013.73 In the published version of this paper, on page 567, on the 16th line in the last paragraph of the left column, the abbreviation of Expected Pathogenic is incorrect. The correct sentence should read, “For the purposes of these recommendations, variants fitting these descriptions were labeled as Known Pathogenic (KP) and Expected Pathogenic (EP), respectively.