Genomic Research Results Research Articles

Researchers' views on informed consent for return of secondary results in genomic research.

Previous studies have suggested that genomic investigators generally favor offering to return at least some secondary findings to participants and believe that participants' preferences should determine the information they receive. We surveyed investigators to ascertain their views on four models of informed consent for this purpose: traditional consent, staged consent, mandatory return, and outsourced consent. We performed an online survey of the views regarding return of secondary results held by 198 US genetic researchers drawn from our subject pool for an earlier study. Potential participants were identified through the National Institutes of Health RePORTER database and abstracts from the 2011 American Society of Human Genetics meeting. Under circumstances in which resource constraints are not an issue, approximately a third of respondents would endorse either staged consent or traditional consent; outsourced consent and mandatory return are favored by only a small minority. However, taking resource constraints into account, roughly half the sample would favor traditional consent, with support for staged consent dropping to 13%. Despite their liabilities, traditional approaches to consent are seen as the most viable under current circumstances. However, there is considerable interest in staged consent, assuming the infrastructure to support it can be provided.

The Evolutionary Genomics of Cichlid Fishes: Explosive Speciation and Adaptation in the Postgenomic Era

With more than 1,500 species, cichlid fishes provide textbook examples of recent and diverse adaptive radiations, rapid rates of speciation, and the parallel evolution of adaptive phenotypes among both recently and distantly related lineages. This extraordinary diversity has attracted considerable interest from researchers across several biological disciplines. Their broad phenotypic variation coupled with recent divergence makes cichlids an ideal model system for understanding speciation, adaptation, and phenotypic diversification. Genetic mapping, genome-wide analyses, and genome projects have flourished in the past decade and have added new insights on the question of why there are so many cichlids. These recent findings also show that the sharing of older DNA polymorphisms is extensive and suggest that linage sorting is incomplete and that adaptive introgression played a role in the African radiation. Here, we review the results of genetic and genomic research on cichlids in the past decade and suggest some potential avenues to further exploit the potential of the cichlid model system to provide a better understanding of the genomics of adaptation and speciation.

Return of Genomic Results to Research Participants: The Floor, the Ceiling, and the Choices In Between

As more research studies incorporate next-generation sequencing (including whole-genome or whole-exome sequencing), investigators and institutional review boards face difficult questions regarding which genomic results to return to research participants and how. An American College of Medical Genetics and Genomics 2013 policy paper suggesting that pathogenic mutations in 56 specified genes should be returned in the clinical setting has raised the question of whether comparable recommendations should be considered in research settings. The Clinical Sequencing Exploratory Research (CSER) Consortium and the Electronic Medical Records and Genomics (eMERGE) Network are multisite research programs that aim to develop practical strategies for addressing questions concerning the return of results in genomic research. CSER and eMERGE committees have identified areas of consensus regarding the return of genomic results to research participants. In most circumstances, if results meet an actionability threshold for return and the research participant has consented to return, genomic results, along with referral for appropriate clinical follow-up, should be offered to participants. However, participants have a right to decline the receipt of genomic results, even when doing so might be viewed as a threat to the participants' health. Research investigators should be prepared to return research results and incidental findings discovered in the course of their research and meeting an actionability threshold, but they have no ethical obligation to actively search for such results. These positions are consistent with the recognition that clinical research is distinct from medical care in both its aims and its guiding moral principles.

Attitudes of parents toward the return of targeted and incidental genomic research findings in children

We describe parental attitudes toward the return of targeted and incidental genomic research results in the setting of high-risk pediatric cancer and inherited childhood diseases. A validated 36-item questionnaire was mailed to participants in three large-scale genome research consortia examining attitudes toward receipt of genomic research results and the influence of certainty, severity, and onset of the condition, in addition to responsibilities to extended family and provision of results even after death of the proband. Of the 563 participants who were sent questionnaires, 362 (64%) responded. Most of them stated a positive right to receive results related to the target condition (97%) or to incidental findings (86%); no difference was found in results between participants with cancer and those with orphan diseases. Furthermore, 92% indicated that genomic research for childhood-onset conditions should occur. The majority wanted incidental results predicting susceptibility even to untreatable fatal conditions (83%), to multiple conditions (87%), or to those with uncertain impact (70%). Most felt sibling genomic results showing serious conditions, whether treatable (93%) or not (88%), and/or results discovered after death of the proband should be shared with family (74%). Many parents of children in pediatric genomic research indicated a strong desire to receive a broader range of results than is described in consensus recommendations. Clear delineation of what will be offered should be established at the time of consent.

Parents' Preferences for Return of Results in Pediatric Genomic Research

Background: The aim of this study was to ascertain parental preferences for the return of genetic research results on themselves and their children and their choices for genetic research results to receive. Methods: A mail survey was sent to 6,874 families seen at Boston Children's Hospital. The survey included questions assessing the respondents' preferences regarding the types of result they wanted to receive on themselves and their children. Results: Most of the 1,060 respondents ‘probably' or ‘definitely' wanted to receive genetic research results about themselves (84.6%) and their children (88.0%). Among those who wanted to receive results, 83.4% wanted to receive all research results for themselves and 87.8% for their children. When questions about specific types of research results were combined into a composite measure, fewer respondents chose to receive all results for themselves (53.5%) and for their children (56.9%). Conclusion: Although most parents report a desire to receive all research results on a general question, almost half chose to receive only a subset of research results when presented with specific types of research results. Our findings suggest that participants might not understand the implications of their choice of individual research results to receive unless faced with specific types of results.

Attitudes to the return of incidental and targeted genomic findings obtained in a high-risk pediatric cancer versus an inherited genetic condition research setting.

10066 Background: The disclosure of clinically significant, validated incidental and target findings to participants in genomic research is often recommended. There have been no reports on whether attitudes of parents differ if these findings emerge from an acquired pediatric cancer versus an inherited genetic condition setting. Methods: Parents in 3 large-scale projects [Canadian Pediatric Cancer Genome Consortium (CPCGC), the Finding of Rare Genes Canada Consortium (FORGE) and the Orphan Diseases: identifying Genes and Novel Therapeutics to Enhance Treatment Project (IGNITE)] were surveyed using a mailed, validated 29-item questionnaire. Two reminders were sent. Analysis was by descriptive and Chi-square statistics. Results: Response rate: 64% (n=307/480). 40% were > 50 yrs age; more than half had a grade 12 education. 86 were parents of poor risk pediatric cancer patients and 221 were parents or individuals with rare inherited conditions. Most stated a very strong or strong right to genomic research results, irrespective if from the target condition (97%) or incidental (86%). 70% wish genetic counselling pre- and post-research testing; an additional 20% were uncertain what this entails. Almost all indicated that genomic research for childhood onset conditions should occur, regardless of whether therapy existed (99%) or not (91%). A few indicated that they would not want incidental results showing an untreatable fatal condition (17%). Most want results, even if these suggest susceptibility to multiple conditions (87%) or are of uncertain health impact (84%). Most felt a right to genomic research that showed a serious condition in siblings, whether treatable (94%) or not (89%). 74% strongly support that results discovered after death of the proband be shared with family. Conclusions: Parents of children in both cancer and inherited rare conditions genomic research do not differ in indicating a strong right and desire to receive research results, even if they are of uncertain impact, of childhood onset, or after death of the proband. Clear delineation of what will or will not be offered from genomic research should be established at the time of consent.

Overcoming the obstacles to returning genomic research results

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Return of results in genomic biobank research: ethics matters

Return of results in genomic biobank research: ethics matters

Attitudes of Canadian researchers toward the return to participants of incidental and targeted genomic findings obtained in a pediatric research setting

Purpose:The purpose of this study was to explore the attitudes of genomics researchers in a pediatric setting in the context of regulatory guidance recommending the disclosure of clinically significant research findings.Methods:A validated 32-item questionnaire was sent to 107 researchers with two large-scale projects (the Canadian Pediatric Cancer Genome Consortium and the Finding of Rare Genes Canada Consortium). We examined researchers' attitudes toward obligations to offer genomic research results (including if the participant was deceased, a relative, or a child), influence of the certainty/severity of the condition on this obligation, and personal experiences.Results:Of the 107 researchers, 74 (69%) responded. Researchers did not feel a strong responsibility to look for meaningful incidental results in the research genomic data set (n = 27, 37%). However, once identified, they felt participants had a strong right to receive them, irrespective of being incidental (n = 50, 68%) or primary targets (n = 64, 87%). There was a high degree of support for informing siblings of genomic results (n = 46, 62%), especially for treatable conditions (n = 56, 76%). Less than half of the participants indicated that their research ethics board required an offer of results (n = 34, 46%) or provided a detailed process (n = 16, 22%).Conclusion:Researchers strongly support the offer of targeted and incidental genomic research results to participants. Greater regulatory guidance is needed for a consistent approach.

The importance of being Uros: Indigenous identity politics in the genomic age

The objective of this article is to explore the interrelations between human population genomic research, the political strategies of indigenous movements and processes of identity formation. It will do so by analysing the collaboration between the Uros, an indigenous group living on artificial floating islands on Lake Titicaca (Peru), and researchers of the Genographic Project. Claiming descent from the ancient Urus, the islands’ inhabitants used their differentiated ethnic identity as a central resource in a territorial conflict with the Peruvian state. Their engagement with genetics was aimed at obtaining scientific support for their highly contested claims. In fact, the results of genomic research became a central element in the debate waged around the identity of the Uros. This article aims to contribute new insights into the incorporation of genetic research within the political debates waged over the identities of indigenous populations, as well as to the interaction of genetic knowledge with pre-existing discourses for defining ethnic identities. It also analyses the ways in which genetic research is turned into a political resource with the ability to generate significant social effects in the daily lives of studied populations.

Attitudes of Researchers to the Return of Incidental and Targeted Genomic Findings Obtained in a Research Setting to Participants

AbstractAbstract 2069 Background:The use of genomic research has exploded in recent years. Various guidelines recommend disclosure of significant, clinically validated findings to participants. Continued debate in this area has led to calls for stakeholder involvement to inform policy. In particular, the attitudes of genomics researchers are salient yet relatively unexplored with respect to how the sharing of both targeted and incidental findings should be accomplished. Methods:All 107 researchers affiliated with two large-scale Genome Canada projects [Canadian Pediatric Cancer Genome Consortium (CPCGC) and the Finding of Rare Genes Canada Consortium (FORGE)] were surveyed using a mailed, validated 32-item questionnaire that had been pilot tested with genomics researchers. The survey was designed to cover a wide range of topics including attitudes of researchers to the return of incidental and targeted research results, the need for genetic counselling, responsibilities to participants over time, to child participants and to siblings of participants, and institutional ethics review. Two reminders were sent to non-respondents. Data were analyzed with descriptive statistics. Results:74/107 (69%) responded. Most were between 41–55 yr of age (n=40, 54%) and had their most senior training inNorth America (n=67, 91%). The majority were experienced researchers (n=58, 78%) and felt comfortable in discussing genomic results with participants (n= 66, 89%). Respondents did not feel a strong responsibility to look for meaningful incidental results in the genomic data set they created (n=27, 37%). However, once potentially significant results were identified, researchers indicated that participants had a strong or very strong right to receive analytically validated genomic results irrespective of whether these results were incidental findings (n= 50, 68%) or primary targets of the research (n= 64, 87%). Most indicated that results with clinical utility that were actionable should be offered to participants (n=54, 73%) although some indicated that research results should not be returned under any circumstances (n=6, 8%). The majority felt that a research result should be confirmed in a clinical lab prior to return to participants (n=51, 69%). Most indicated that genetic counselling should be provided either almost always or frequently prior to genomic research participation (n=48, 64%). Respondents indicated that siblings of genomic research participants had a strong or very strong right to be informed of results (n=46, 62%), and this was especially true if an intervention to ameliorate the identified condition is feasible (n=56, 76%). A minority of researchers felt personal responsibility to ensure genomic research results obtained on a child of potential clinical utility were eventually communicated to him/her when the child became an adult (n=10, 14%). A slim majority felt the parents or health care provider should be responsible (n=38, 51%). Some researchers reported encountering incidental findings of clinical utility (n=25, 34%) and had offered them to participants. However, the minority reported that their institutional ethics review boards either always (n=10, 14%) or sometimes (n=24, 32%) required an offer of results. Only 16 (22%) indicated that their ethics board had a detailed process on how to do so. Conclusions:Researchers in general support the offer of return of targeted and incidental genomic research results to participants. A minority strongly oppose such action. There is typically a high degree of support for the offer of genomic research findings to siblings, especially if actionable. Given the new developments in genomics and resulting incidental findings, researchers describe little specific guidance about the process that should be followed in returning results to participants. Greater policy guidance would be of assistance in providing a consistent approach to the offer of incidental or targeted genomic research results. Acknowledgments:Funded by Genome Canada and the Canadian Institutes of Health Research. Disclosures:No relevant conflicts of interest to declare.

A closer look revisited: are we subjects or are we donors?

The author offers personal reflections on the implications of the article “Managing Incidental Findings & Research Results in Genomic Research Involving Biobanks & Archived Datasets” in terms of how the article addresses serious knowledge disparities and differing expectations between participants and researchers.Genet Med 2012:14(4):458–460

The past, present, and future of the debate over return of research results and incidental findings

In this introduction to a symposium on managing incidental findings (IFs) and individual research results (IRRs) in genomic research involving biobanks and archived datasets, the principal investigator of the underlying NIH-funded project discusses the roots, current state, and likely future of this debate. The roots lie in the recognition that research participants are not mere means to scientific progress, but vulnerable individuals. After key position papers on return of IFs and IRRs by investigators, the debate has now turned to the more complex question addressed in this symposium--how large-scale research using biobanks and archived datasets should approach IFs and IRRs. Where is the debate headed next? The answer lies in the history itself, a history of progress toward recognizing the humanity and informational needs of research participants. Increasingly, participants will be offered individual information. Limits will be set, to preserve the capacity to perform research and to protect participants from faulty information. And not all studies and biobanks will undertake individual return. It will take research and work to tailor return to serve participants’ needs and research realities. But debating return is the next step toward recognizing those who contribute specimens and data as partners in the research process.

The beliefs, motivations, and expectations of parents who have enrolled their children in a genetic biorepository

PurposeLittle is known about parental attitudes toward return of individual research results (IRRs) in pediatric genomic research. The aim of this study was to understand the views of the parents who enrolled their children in a genomic repository in which IRRs will be returned. MethodsWe conducted focus groups with parents of children with developmental disorders enrolled in the Gene Partnership (GP), a genomic research repository that offers to return IRRs, to learn about their understanding of the GP, motivations for enrolling their children, and expectations regarding the return of IRRs. ResultsParents hoped to receive IRRs that would help them better understand their children’s condition(s). They understood that this outcome was unlikely, but hoped that their children’s participation in the GP would contribute to scientific knowledge. Most parents wanted to receive all IRRs about their child, even for diseases that were severe and untreatable, citing reasons of personal utility. Parents preferred electronic delivery of the results and wanted to designate their preferences regarding what information they would receive. ConclusionIt is important for researchers to understand participant expectations in enrolling in a research repository that offers to disclose children’s IRRs in order to effectively communicate the implications to parents during the consenting process.Genet Med 2012:14(3):330–337

Individual genetic and genomic research results and the tradition of informed consent: exploring US review board guidance

BackgroundGenomic research is challenging the tradition of informed consent. Genomic researchers in the USA, Canada and parts of Europe are encouraged to use informed consent to address the prospect of...

A Metaphor Made in Public

The preliminary results of human genome research have become widely known as “drafts of the human genome.” Drawing on the interaction theory of metaphor, this article shows that take-up of the notion of a draft and its elaboration as a scientific metaphor was contingent on interactions with broader audiences.The notion of a draft was thus not merely a metonym of the popular but often-criticized Book of Life metaphor for the human genome.

What is a meaningful result? Disclosing the results of genomic research in autism to research participants

Developments in genomics research have been accompanied by a controversial ethical injunction: that researchers disclose individually relevant research results to research participants. With the explosion of genomic research on complex psychiatric conditions such as autism, researchers must increasingly contend with whether--and which results--to report. We conducted a qualitative study with researchers and participants involved in autism genomics research, including 4 focus groups and 23 interviews with parents of autistic children, and 23 interviews with researchers. Respondents considered genomic research results 'reportable' when results were perceived to explain cause, and answer the question 'why;' that is, respondents set a standard for reporting individually relevant genetic research results to individual participants that is specific to autism, reflecting the metaphysical value that genetic information is seen to offer in this context. In addition to this standard of meaning, respondents required that results be deemed 'true.' Here, respondents referenced standards of validity that were context nonspecific. Yet in practice, what qualified as 'true' depended on evidentiary standards within specific research disciplines as well as fundamental, and contested, theories about how autism is 'genetic.' For research ethics, these finding suggest that uniform and context-free obligations regarding result disclosure cannot readily be specified. For researchers, they suggest that result disclosure to individuals should be justified not only by perceived meaning but also by clarity regarding appropriate evidentiary standards, and attention to the status of epistemological debates regarding the nature and cause of disorders.

Regularities of the location of genes having different functions and of some other nucleotide sequences in the bacterial chromosome

The review considers the results of genomic research performed over the last decade that shed light on the location in the bacterial chromosomes of genes having different functions. A tendency towards polarity of the chromosome composition is observed: vitally important genes tend to be concentrated in the region of replication origin (oriC), and their concentration decreases toward the region of replication termination (terC). An oppositely directed polarity (an increase near the terC region) is observed for the distribution of certain oligonucleotides involved in the process of chromosome recombination and segregation.

Tumor Proteomics - Neue Wege in der Diagnostik kolorektaler Karzinome

Die Frühdiagnose des kolorektalen Karzinoms respektive der zum Malignom führenden Vorstufen ist der Schlüssel zur kurativen Therapie dieser Erkrankung. Trotz Screening-Methoden werden über zwei Drittel aller kolorektalen Karzinome erst im Stadium III und IV diagnostiziert und bedingen so die schlechte Prognose. Die Proteomforschung („PROTEins expressed by a genOME”) ist ein neues Feld der Wissenschaft, in dem Zusammensetzung, Struktur, Funktion und Interaktion von Polypeptiden untersucht werden, die als potenzielle Biomarker zur Früherkennung fungieren können. Schon heute sind Proteomanalysen auf Basis der zweidimensionalen Gelelektrophorese (2-DE), der Massenspektrometrie (MALDI) und der SELDI-Technologie in der Lage, mit hoher Sensitivität und Spezifität den Tumorerkrankten vom Gesunden zu unterscheiden. Die Identifikation tumorentitätsspezifischer Markerproteine wird es zukünftig möglich machen, personalisierte Behandlungsstrategien zu entwickeln und birgt somit das Potenzial, die Überlebensraten von Patienten mit kolorektalen Karzinomen deutlich zu beeinflussen. Es ist vorhersehbar, dass in naher Zukunft die klinische Medizin die Ergebnisse der Proteom- und Genomforschung in die Routine integrieren wird. Bei diesem Transfer von „bench to bedside” wird dem Chirurgen eine tragende Rolle zukommen.

Preemptive patenting, human genomics, and the US biotechnology sector: balancing intellectual property rights with societal welfare

Within the biotechnology sector of the US economy, aggressive patenting, i.e. preemptive patenting, of human genomic research results are practiced by private-sector firms, the academic community, and non-profit organizations. Preemptive patenting has traditionally been practiced by the private sector as a competitive strategy, being driven by economic considerations. Recently, academics and patients/consumers have instituted preemptive patenting strategies as a way of ensuring access to genomic sequences for, respectively, research study purposes and life-enhancing access to diagnostic gene testing. To reduce this non-economic motivation for preemptive patenting by these nontraditional competitors, it is recommended that the biotechnology industry initiate a strategy of its own which will: (1) relax firm patent enforcement of genomic sequences that are essential for academic researchers to use in their studies; and (2) provide for a ‘means-test’ approach that incorporates a ‘staggered’ fee-schedule for academic researchers to charge their subjects, i.e. patients, for gene tests and diagnostic results.