Genomic Medicine Research Research Articles

Co-creating the experience of consent for newborn genome sequencing (The Generation Study).

The Generation Study (GS) aims to recruit 100,000 newborns in England to evaluate the utility and feasibility of using whole genome sequencing to screen for rare conditions that can be treated in early childhood; enable wider research to support further discovery in genomics and health; and explore the potential of storing an individual's genome over their lifetime. The GS incorporates complexities of consent in newborn screening, genomic medicine, and healthcare research, and there is a gap in exploring how to implement existing recommendations. Participant involvement has been shown to improve the implementation of processes and materials in healthcare. This paper describes how the GS team leveraged this through Design Research (DR) methodologies to develop the GS consent experience. Over a two-year period, 9 rounds of DR were undertaken with expectant and recent parents and a chosen partner (n=105). Each round consisted of semi-structured interviews and a range of co-design and usability testing activities. DR activities highlighted areas for consideration when consent materials and processes. We describe common barriers and enablers across three stages of consent: awareness, consideration, and making an informed decision. As well as ensuring participants fully understand pros and cons of taking part, materials should consider pre-existing assumptions or misconceptions which may discourage parents from learning about the GS. Involving parents in co-creation has broadened the perspective of what constitutes informed decision-making for newborn genome sequencing. Iterative rounds of research and design can provide tangible paths forward, supporting the successful implementation of informed decision-making.

Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals.

Background: The current study explores the genetic underpinnings of cardiac arrhythmia phenotypes within Middle Eastern populations, which are under-represented in genomic medicine research. Methods: Whole-genome sequencing data from 14,259 individuals from the Qatar Biobank were used and contained 47.8% of Arab ancestry, 18.4% of South Asian ancestry, and 4.6% of African ancestry. The frequency of rare functional variants within a set of 410 candidate genes for cardiac arrhythmias was assessed. Polygenic risk score (PRS) performance for atrial fibrillation (AF) prediction was evaluated. Results: This study identified 1196 rare functional variants, including 162 previously linked to arrhythmia phenotypes, with varying frequencies across Arab, South Asian, and African ancestries. Of these, 137 variants met the pathogenic or likely pathogenic (P/LP) criteria according to ACMG guidelines. Of these, 91 were in ACMG actionable genes and were present in 1030 individuals (~7%). Ten P/LP variants showed significant associations with atrial fibrillation p < 2.4 × 10-10. Five out of ten existing PRSs were significantly associated with AF (e.g., PGS000727, p = 0.03, OR = 1.43 [1.03, 1.97]). Conclusions: Our study is the largest to study the genetic predisposition to arrhythmia phenotypes in the Middle East using whole-genome sequence data. It underscores the importance of including diverse populations in genomic investigations to elucidate the genetic landscape of cardiac arrhythmias and mitigate health disparities in genomic medicine.

Microarray Images Contrast Enhancement and Gridding Using Genetic Algorithm.

Microarray is a sophisticated tool that concurrently analyzes the expression levels of thousands of genes, giving scientists an overview of DNA and RNA study. This procedure is divided into three stages: contact with biological samples, data extraction, and data analysis. Because expression levels are disclosed by the interplay of light with fluorescent markers, the data extraction stage relies on image processing methods. To extract quantitative information from the microarray image (MAI), four steps of preprocessing, gridding, segmentation, and intensity quantification are required. During the generation of MAIs, a large number of error-prone processes occur, leading to structural problems and reduced quality in the resulting data, affecting the identification of expressed genes. In this article, the first stage has been examined. In the preprocessing stage, the contrast of the images is first enhanced using the genetic algorithm, then the source noises that appear as small artifacts are removed using morphology, and finally, to confirm the effect of the contrast enhancement (CE) on the main stages of microarray data processing, gridding is checked on complementary deoxyribonucleic acid MAIs. The comparison of the obtained results with an adaptive histogram equalization (AHE) and multi-decomposition histogram equalization (M-DHE) methods shows the superiority and efficiency of the proposed method. For example, the image contrast of the Genomic Medicine Research Center Laboratory dataset is 3.24, which is 42.91 with the proposed method and 13.48 and 32.40 with the AHE and M-DHE methods, respectively. The performance of the proposed methods for CE is evaluated on 3 databases and a general conclusion is obtained as to which CE method is more suitable for each dataset.

Industry involvement in evidence production for genomic medicine: A bibliometric and funding analysis of decision impact studies.

Decision impact studies have become increasingly prevalent in genomic medicine, particularly in cancer research. Such studies are designed to provide evidence of clinical utility for genomic tests by evaluating their impact on clinical decision-making. This paper offers insights into understanding of the origins and intentions of these studies through an analysis of the actors and institutions responsible for the production of this new type of evidence. We conducted bibliometric and funding analyses of decision impact studies in genomic medicine research. We searched databases from inception to June 2022. The datasets used were primarily from Web of Science. Biblioshiny, additional R-based applications, and Microsoft Excel were used for publication, co-authorship and co-word analyses. 163 publications were included for the bibliometric analysis; a subset of 125 studies were included for the funding analysis. Included publications started in 2010 and increased steadily over time. Decision impact studies were primarily produced for proprietary genomic assays for use in cancer care. The author and affiliate analyses reveal that these studies were produced by 'invisible colleges' of researchers and industry actors with collaborations focused on producing evidence for proprietary assays. Most authors had an industry affiliation, and the majority of studies were funded by industry. While studies were conducted in 22 countries, the majority had at least one author from the USA. This study is a critical step in understanding the role of industry in the production of new types of research. Based on the data collected, we conclude that decision impact studies are industry-conceived and -produced evidence. The findings of this study demonstrate the depth of industry involvement and highlight a need for further research into the use of these studies in decision-making for coverage and reimbursement.

Equity in Genomic Medicine.

Since the completion of the Human Genome Project, considerable progress has been made in translating knowledge about the genetic basis of disease risk and treatment response into clinical services and public health interventions that have greater precision. It is anticipated that more precision approaches to early detection, prevention, and treatment will be developed and will enhance equity in healthcare and outcomes among disparity populations. Reduced access to genomic medicine research, clinical services, and public health interventions has the potential to exacerbate disparities in genomic medicine. The purpose of this article is to describe these challenges to equity in genomic medicine and identify opportunities and future directions for addressing these issues. Efforts are needed to enhance access to genomic medicine research, clinical services, and public health interventions, and additional research that examines the clinical utility of precision medicine among disparity populations should be prioritized to ensure equity in genomic medicine.

Automatic DNA replication tract measurement to assess replication and repair dynamics at the single-molecule level.

MotivationDNA fibre assay has a potential application in genomic medicine, cancer and stem cell research at the single-molecule level. A major challenge for the clinical and research implementation of DNA fibre assays is the slow speed in which manual analysis takes place as it limits the clinical actionability. While automatic detection of DNA fibres speeds up this process considerably, current publicly available software have limited features in terms of their user interface for manual correction of results, which in turn limit their accuracy and ability to account for atypical structures that may be important in diagnosis or investigative studies. We recognize that core improvements can be made to the GUI to allow for direct interaction with automatic results to preserve accuracy as well as enhance the versatility of automatic DNA fibre detection for use in variety of situations.ResultsTo address the unmet needs of diverse DNA fibre analysis investigations, we propose DNA Stranding, an open-source software that is able to perform accurate fibre length quantification (13.22% mean relative error) and fibre pattern recognition (R > 0.93) with up to six fibre patterns supported. With the graphical interface, we developed, user can conduct semi-automatic analyses which benefits from the advantages of both automatic and manual processes to improve workflow efficiency without compromising accuracy.Availability and implementationThe software package is available at https://github.com/lgole/DNAStranding.Supplementary information Supplementary data are available at Bioinformatics online.

Genomics in Egypt: Current Status and Future Aspects.

Egypt is the third most densely inhabited African country. Due to the economic burden and healthcare costs of overpopulation, genomic and genetic testing is a huge challenge. However, in the era of precision medicine, Egypt is taking a shift in approach from “one-size-fits all” to more personalized healthcare via advancing the practice of medical genetics and genomics across the country. This shift necessitates concrete knowledge of the Egyptian genome and related diseases to direct effective preventive, diagnostic and counseling services of prevalent genetic diseases in Egypt. Understanding disease molecular mechanisms will enhance the capacity for personalized interventions. From this perspective, we highlight research efforts and available services for rare genetic diseases, communicable diseases including the coronavirus 2019 disease (COVID19), and cancer. The current state of genetic services in Egypt including availability and access to genetic services is described. Drivers for applying genomics in Egypt are illustrated with a SWOT analysis of the current genetic/genomic services. Barriers to genetic service development in Egypt, whether economic, geographic, cultural or educational are discussed as well. The sensitive topic of communicating genomic results and its ethical considerations is also tackled. To understand disease pathogenesis, much can be gained through the advancement and integration of genomic technologies via clinical applications and research efforts in Egypt. Three main pillars of multidisciplinary collaboration for advancing genomics in Egypt are envisaged: resources, infrastructure and training. Finally, we highlight the recent national plan to establish a genome center that will aim to prepare a map of the Egyptian human genome to discover and accurately determine the genetic characteristics of various diseases. The Reference Genome Project for Egyptians and Ancient Egyptians will initialize a new genomics era in Egypt. We propose a multidisciplinary governance system in Egypt to support genomic medicine research efforts and integrate into the healthcare system whilst ensuring ethical conduct of data.

Prevalence and prediction of medical distrust in a diverse medical genomic research sample

PurposeMedical distrust has been identified as a persistent barrier to medical care, affecting preventative screening, treatment uptake, and treatment adherence. Despite this, little research to date has examined medical distrust in a genomic medicine context. The goal of this work was to assess the prevalence of medical distrust in a genomic medicine research study and examine patient-level demographic, access-related, and health-status characteristics that predict medical distrust. MethodsWe assessed medical distrust in a research sample of adults (N = 967) receiving genomic sequencing to screen for hereditary risk of cancer syndromes in the United States. We used multiple predictive variable selection models to determine predictors of medical distrust followed by marginal mean analyses to characterize the relationships. ResultsThe prevalence of medical distrust was 32%. The final model indicated that Black and African American race/ethnicity; trans, nonbinary, or nonidentifying gender identity; high education; low income; low access to health care; and poor Short Form 12 mental health composite scores predict medical distrust. ConclusionMedical distrust may pose similar challenges to genomic sequencing, as it does in other medical contexts. The pattern of variables that predict distrust suggest that increasing access and accommodation for stigmatized and underserved communities may help overcome the negative effects of medical distrust.

Adapting a conceptual framework to engage diverse stakeholders in genomic/precision medicine research.

IntroductionGenomic/precision medicine offers a remarkable opportunity to improve health and address health disparities. Genomic medicine is the study of genes and their interaction with health. Precision medicine is an approach to disease prevention and treatment that considers individual variability in genes, environment and lifestyle. Conclusions from studies lacking diversity may hinder generalizability as genomic variation occurs within and between populations. Historical factors, such as medical mistrust, ethical issues related to decision making, and data sharing pose complex challenges that may further widen inequities in genomic/precision medicine if not appropriately addressed. Although few biomedical studies integrate priorities of community partners into their conceptual framework, effective implementation of genomic/precision medicine research calls for the involvement of diverse stakeholders to expand traditional unidirectional models of engagement in clinical research towards authentic bidirectional collaboration.MethodsA multipronged approach was used integrating an evidence‐based literature review and best practices in developing and evaluating the engagement of diverse stakeholders in genomic and precision medicine research. This was combined with expert consensus building to adapt a conceptual model from a community engagement framework to addressing genomics to be scalable to engagement science, which is challenging to genomic/precision medicine research.ResultsThe final enhanced conceptual framework is composed of four overarching dimensions now inclusive of domains in trust, exploitation, discrimination, privacy risk, stigmatization, prior harms/injustices, failure to recognize coexisting governments, intersectionality and research transformation. This conceptual framework proposes effective participant research engagement strategies for upstream relationship building, distinct from downstream recruitment strategies in which the goal is enrolment.ConclusionTo further shape the evolution of genomic/precision medicine research, it is important to leverage existing partnerships, engage participants beyond recruitment and embrace diverse perspectives.Patient or Public ContributionIn preparation of this manuscript, the perspectives of the community partners on the impact of engaging in genomic/precision medicine research beyond research participation were integrated into this conceptual framework from various guided listening sessions held in diverse communities.

Integration of stakeholder engagement from development to dissemination in genomic medicine research: Approaches and outcomes from the CSER Consortium

PurposeThere is a critical need for genomic medicine research that reflects and benefits socioeconomically and ancestrally diverse populations. However, disparities in research populations persist, highlighting that traditional study designs and materials may be insufficient or inaccessible to all groups. New approaches can be gained through collaborations with patient/community stakeholders. Although some benefits of stakeholder engagement are recognized, routine incorporation into the design and implementation of genomics research has yet to be realized. MethodsThe National Institutes of Health–funded Clinical Sequencing Evidence-Generating Research (CSER) consortium required stakeholder engagement as a dedicated project component. Each CSER project planned and carried out stakeholder engagement activities with differing goals and expected outcomes. Examples were curated from each project to highlight engagement strategies and outcomes throughout the research lifecycle from development through dissemination. ResultsProjects tailored strategies to individual study needs, logistical constraints, and other challenges. Lessons learned include starting early with engagement efforts across project stakeholder groups and planned flexibility to enable adaptations throughout the project lifecycle. ConclusionEach CSER project used more than 1 approach to engage with relevant stakeholders, resulting in numerous adaptations and tremendous value added throughout the full research lifecycle. Incorporation of community stakeholder insight improves the outcomes and relevance of genomic medicine research.

Genome sequencing as a first-line diagnostic test for hospitalized infants

PurposeSouthSeq is a translational research study that undertook genome sequencing (GS) for infants with symptoms suggestive of a genetic disorder. Recruitment targeted racial/ethnic minorities and rural, medically underserved areas in the Southeastern United States, which are historically underrepresented in genomic medicine research. MethodsGS and analysis were performed for 367 infants to detect disease-causal variation concurrent with standard of care evaluation and testing. ResultsDefinitive diagnostic (DD) or likely diagnostic (LD) genetic findings were identified in 30% of infants, and 14% of infants harbored an uncertain result. Only 43% of DD/LD findings were identified via concurrent clinical genetic testing, suggesting that GS testing is better for obtaining early genetic diagnosis. We also identified phenotypes that correlate with the likelihood of receiving a DD/LD finding, such as craniofacial, ophthalmologic, auditory, skin, and hair abnormalities. We did not observe any differences in diagnostic rates between racial/ethnic groups. ConclusionWe describe one of the largest-to-date GS cohorts of ill infants, enriched for African American and rural patients. Our results show the utility of GS because it provides early-in-life detection of clinically relevant genetic variations not detected by current clinical genetic testing, particularly for infants exhibiting certain phenotypic features.

Introducing The International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD)

The International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) is a £5 m, 5 year MRC Strategic award whose goal is to improve health outcomes for people with neuromuscular diseases (NMDs) globally. Activity is distributed across 14 Centres in Brazil, India, Turkey, South Africa, the United Kingdom and Zambia. The ICGNMD aims to: • deliver an international genomics research & capacity-building partnership in genomic medicine; • facilitate international NMD patient access to accurate genetic diagnoses; • assemble “trial ready” comprehensively phenotyped and genotyped cohorts of people living with NMDs and their families; and growing clinical capacity in neuromuscular diseases by training a cohort of clinical academic researchers.

Revisiting Secondary Information Related to Pharmacogenetic Testing.

Incidental or secondary findings have been a major part of the discussion of genomic medicine research and clinical applications. For pharmacogenetic (PGx) testing, secondary findings arise due to the pleiotropic effects of pharmacogenes, often related to their endogenous functions. Unlike the guidelines that have been developed for whole exome or genome sequencing applications for management of secondary findings (though slightly different from PGx testing in that these refer to detection of variants in multiple genes, some with clinical significance and actionability), no corresponding guidelines have been developed for PGx clinical laboratories. Nonetheless, patient and provider education will remain key components of any PGx testing program to minimize adverse responses related to secondary findings.

Public trust and genomic medicine in Canada and the UK.

Background: Genomic medicine could improve precise risk stratification, early prevention, and personalised treatment across a broad spectrum of disease. As this reality approaches, questions on the importance of public trust arise. The success of genomic medicine initiatives is influenced by the public's trust and willingness to engage. Specific social actors influential in the public's trust have been identified by the "Your DNA, Your Say" study, including doctors, researchers, and governments. This paper aims to identify and examine which specific social actors, if any, in Canada and the United Kingdom (UK) are the most trustworthy and influential to engage the public in genomic medicine research. Methods: Using data from the 'Your DNA, Your Say' study, logistic regression models and Pearson's chi-square tests were conducted to explore trust in social actors across Canada and the UK. Results: The results demonstrate Canada and the UK significantly differ in public trust and willingness to donate. Non-profit researchers, domestic doctors, and personal doctors were identified to be the most influential and trustworthy social actors in Canada and the UK. Conclusions: The comparative results indicate that both countries would benefit from engaging the public through doctors and non-profit researchers. The UK could additionally support public trust by engaging with the public through the National Health Service. However, the results suggest that whilst public trust is significant, it may be neither necessary nor sufficient in influencing willingness to donate. Future research could do well to investigate how the importance of public trust compares in countries with lower public trust.

Public trust and genomic medicine in Canada and the UK

Background: Genomic medicine could improve precise risk stratification, early prevention, and personalised treatment across a broad spectrum of disease. As this reality approaches, questions on the importance of public trust arise. The success of genomic medicine initiatives is influenced by the public’s trust and willingness to engage. Specific social actors influential in the public's trust have been identified by the “Your DNA, Your Say” study, including doctors, researchers, and governments. This paper aims to identify and examine which specific social actors, if any, in Canada and the United Kingdom (UK) are the most trustworthy and influential to engage the public in genomic medicine research. Methods: Using data from the ‘Your DNA, Your Say’ study, logistic regression models and Pearson’s chi-square tests were conducted to explore trust in social actors across Canada and the UK. Results: The results demonstrate Canada and the UK significantly differ in public trust and willingness to donate. Non-profit researchers, domestic doctors, and personal doctors were identified to be the most influential and trustworthy social actors in Canada and the UK. Conclusions: The comparative results indicate that both countries would benefit from engaging the public through doctors and non-profit researchers. The UK could additionally support public trust by engaging with the public through the National Health Service. However, the results suggest that whilst public trust is significant, it may be neither necessary nor sufficient in influencing willingness to donate. Future research could do well to investigate how the importance of public trust compares in countries with lower public trust.

Evaluating the clinical utility of early exome sequencing in diverse pediatric outpatient populations in the North Carolina Clinical Genomic Evaluation of Next-generation Exome Sequencing (NCGENES) 2 study: a randomized controlled trial

BackgroundExome sequencing (ES) has probable utility for shortening the diagnostic odyssey of children with suspected genetic disorders. This report describes the design and methods of a study evaluating the potential of ES as a routine clinical tool for pediatric patients who have suspected genetic conditions and who are in the early stages of the diagnostic odyssey.MethodsThe North Carolina Clinical Genomic Evaluation by Next-generation Exome Sequencing (NCGENES) 2 study is an interdisciplinary, multi-site Phase III randomized controlled trial of two interventions: educational pre-visit preparation (PVP) and offer of first-line ES. In this full-factorial design, parent-child dyads are randomly assigned to one of four study arms (PVP + usual care, ES + usual care, PVP + ES + usual care, or usual care alone) in equal proportions. Participants are recruited from Pediatric Genetics or Neurology outpatient clinics in three North Carolina healthcare facilities. Eligible pediatric participants are < 16 years old and have a first visit to a participating clinic, a suspected genetic condition, and an eligible parent/guardian to attend the clinic visit and complete study measures. The study oversamples participants from underserved and under-represented populations. Participants assigned to the PVP arms receive an educational booklet and question prompt list before clinical interactions. Randomization to offer of first-line ES is revealed after a child’s clinic visit. Parents complete measures at baseline, pre-clinic, post-clinic, and two follow-up timepoints. Study clinicians provide phenotypic data and complete measures after the clinic visit and after returning results. Reportable study-related research ES results are confirmed in a CLIA-certified clinical laboratory. Results are disclosed to the parent by the clinical team. A community consultation team contributed to the development of study materials and study implementation methods and remains engaged in the project.DiscussionNCGENES 2 will contribute valuable knowledge concerning technical, clinical, psychosocial, and health economic issues associated with using early diagnostic ES to shorten the diagnostic odyssey of pediatric patients with likely genetic conditions. Results will inform efforts to engage diverse populations in genomic medicine research and generate evidence that can inform policy, practice, and future research related to the utility of first-line diagnostic ES in health care.Trial registrationClinicalTrials.govNCT03548779. Registered on June 07, 2018.

African American Nurses' Perspectives on Genomic Medicine Research.

There is a lack of African American (AA) community engagement in genomic medicine research. Recent popular interest in the experience of AAs, such as that of Henrietta Lacks, has perhaps prompted interest in research on how AA nurses can provide strategies to better engage AA communities in genomic medicine research. The authors conducted one-on-one semi-structured interviews with 11 National Black Nurses Association (NBNA) chapter leaders from 8 different US states, representing 782 NBNA members. Our results quantified NBNA chapter leader agreement on known themes from the literature, captured newly emerging themes, and produced a set of actionable strategies to help overcome barriers to AA engagement in genomic medicine research that fall under 6 themes: (1) engagement, support, information dissemination, and implementation recommendations in general and to address health disparities; (2) addressing language barriers; (3) addressing research implementation barriers; (4) getting physicians to participate; (5) overcoming privacy concerns; and (6) nursing education recommendations. Actionable strategies presented herein can help researchers better engage AA communities in genomic medicine research.

Implementing genomic screening in diverse populations

BackgroundPopulation-based genomic screening has the predicted ability to reduce morbidity and mortality associated with medically actionable conditions. However, much research is needed to develop standards for genomic screening and to understand the perspectives of people offered this new testing modality. This is particularly true for non-European ancestry populations who are vastly underrepresented in genomic medicine research. Therefore, we implemented a pilot genomic screening program in the BioMe Biobank in New York City, where the majority of participants are of non-European ancestry.MethodsWe initiated genomic screening for well-established genes associated with hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), and familial hypercholesterolemia (FH). We evaluated and included an additional gene (TTR) associated with hereditary transthyretin amyloidosis (hATTR), which has a common founder variant in African ancestry populations. We evaluated the characteristics of 74 participants who received results associated with these conditions. We also assessed the preferences of 7461 newly enrolled BioMe participants to receive genomic results.ResultsIn the pilot genomic screening program, 74 consented participants received results related to HBOC (N = 26), LS (N = 6), FH (N = 8), and hATTR (N = 34). Thirty-three of 34 (97.1%) participants who received a result related to hATTR were self-reported African American/African (AA) or Hispanic/Latinx (HL), compared to 14 of 40 (35.0%) participants who received a result related to HBOC, LS, or FH. Among the 7461 participants enrolled after the BioMe protocol modification to allow the return of genomic results, 93.4% indicated that they would want to receive results. Younger participants, women, and HL participants were more likely to opt to receive results.ConclusionsThe addition of TTR to a pilot genomic screening program meant that we returned results to a higher proportion of AA and HL participants, in comparison with genes traditionally included in genomic screening programs in the USA. We found that the majority of participants in a multi-ethnic biobank are interested in receiving genomic results for medically actionable conditions. These findings increase knowledge about the perspectives of diverse research participants on receiving genomic results and inform the broader implementation of genomic medicine in underrepresented patient populations.

\u2018CTRL\u2019: an online, Dynamic Consent and participant engagement platform working towards solving the complexities of consent in genomic research

The complexities of the informed consent process for participating in research in genomic medicine are well-documented. Inspired by the potential for Dynamic Consent to increase participant choice and autonomy in decision-making, as well as the opportunities for ongoing participant engagement it affords, we wanted to trial Dynamic Consent and to do so developed our own web-based application (web app) called CTRL (control). This paper documents the design and development of CTRL, for use in the Australian Genomics study: a health services research project building evidence to inform the integration of genomic medicine into mainstream healthcare. Australian Genomics brought together a multi-disciplinary team to develop CTRL. The design and development process considered user experience; security and privacy; the application of international standards in data sharing; IT, operational and ethical issues. The CTRL tool is now being offered to participants in the study, who can use CTRL to keep personal and contact details up to date; make consent choices (including indicate preferences for return of results and future research use of biological samples, genomic and health data); follow their progress through the study; complete surveys, contact the researchers and access study news and information. While there are remaining challenges to implementing Dynamic Consent in genomic research, this study demonstrates the feasibility of building such a tool, and its ongoing use will provide evidence about the value of Dynamic Consent in large-scale genomic research programs.

Lessons learned from the eMERGE Network: balancing genomics in discovery and practice

SummaryThe Electronic Medical Records and Genomics (eMERGE) Network, established in 2007, is a consortium of academic and integrated health systems conducting discovery and implementation research in translational genomics. Here, we outline the history of the network, highlight major impacts and lessons learned, and present the tools and resources developed for large-scale genomic analyses and translation into a clinical setting. The network developed methods to extract phenotypes from the electronic medical record to perform genome-wide and phenome-wide association studies. Recruited cohorts were clinically sequenced off a custom panel for targeted sequencing of variants and monogenic disease risks and returned to participants to investigate the impact of return of genomic results. After generating a 105,000 participant-imputed genome-wide association study (GWAS) dataset for discovery, the network enrolled and sequenced 24,998 participants. Integration of these results into the medical record and the effects of results on participants provided key lessons to the field. These learned lessons inform genetic research in diverse populations and provide insights into the clinical impact of return and implementation of genomic medicine using the electronic medical record. The lessons produced by the eMERGE Network can be utilized by other consortia as translational genomic medicine research evolves.