CERC CERCSURVEY EHRI Genomics Pediatrics Phenotyping PGx ROR

The Network is is focused on genomic medicine discovery and implementation research utilizing large bioreposititories that are linked to electronic health record (EHR) systems.  The eMERGE workgroups are organized around the Network’s core focus areas: Clinical Annotation, EHR Integration, Genomics, Phenotyping, Outcomes, and Return of Results/Ethical, Legal and Social Implications.

Each workgroup holds monthly conference calls. Published manuscripts and other notable products from our workgroups can be found on the Publications page.

Clinical Annotation

Chairpersons: Heidi Rehm (Partners/Broad) & Gail Jarvik (Kaiser Permanente Washington/University of Washington)

The Clinical Annotation workgroup will focus on activities that build consistency of approaches to the gene and variant interpretation across the eMERGE sequencing centers and study sites as well as support contribution to public knowledge bases.

    • Apply the ClinGen approach to gene-disease validity assessment to all genes on the eMERGE gene panel (including SNP genes), defining each associated condition and the strength of evidence
    • Develop consistency in variant interpretation approaches
    • Compare variant interpretations from CSGs and eMERGE sites on all previously  classified variants in genes in the eMERGE gene panel via comparison of ClinVar submissions

Identify and resolve all differences (prioritize most common and most different)

      • Develop consensus on the most common clinically reportable variants in the eMERGE panel and whether to recommend return to patients
      • Evaluate evidence for pathogenicity (monogenic disease) or contribution to phenotype (PGx, risk alleles)
      • Work jointly with the ROR/ELSI WG to decide categories of variants to return (by phenotype/condition, gene-disease validity level, actionability, penetrance, diagnostic vs SFs, etc.)
      • Facilitate regular ClinVar submissions for all variants interpreted for the eMERGE program
      • Work with the ROR/ELSI WG to develop an environment for ongoing discussion and sharing of challenging genes, cases and variants considered for return (prospective or retrospective)
      • Work jointly with the ROR/ELSI WG to gather feedback and develop consensus on standard language used in clinical reports

EHR Integration

Chairpersons: Sandy Aronson (Harvard) & Casey Overby (Geisinger / Johns Hopkins University)

The EHRI workgroup will focus on the following areas of research in Phase III:

        • Engineering: Establish, document and seek to continuously improve process flows for delivery of eMERGE reports and data
        • Science: Experiment with innovative approaches that go beyond core requirements and evaluate their effectiveness
        • Community: Liaise with other groups, engage in collaborative projects, difsseminate learning and best practices


Chairpersons: Megan Roy-Puckelwartz (Northwestern), Patrick Sleiman (CHOP) & David Crosslin (KPW/UW)

The Genomics workgroup will identify best practices and facilitate analyses to assess the phenotypic impact of common and rare variant data arising from eMERGE II and III. eMERGE has produced a number of GWAS with nearly significant hits or significant hits that require validation/replication. The Genomics workgroup will:

            • Coordinate further analysis of these datasets utilizing imputation with HRC of the eMERGE II data
            • Coordinate integration of GWAS from two new sites
            • Identify datasets that can either be bolstered or replicated by existing data at new eMERGE sites and facilitate exchange of data
            • Interact with the CC and SC to identify and test possible QC and analysis pipelines for rare variant association testing
            • Determine if preexisting sequencing standards are appropriate for the genes sequenced in the eMERGE III cohort.

In conjunction with the Phenotyping working group the Genomics workgroup will:

            • Identify/compile existing phenotype data
            • Create/maximize a central, highly detailed database for what data exists
            • Systematically evaluate where data can be enhanced
            • Prioritize data points that would be most powerful for both eMERGE II and eMERGE III data
            • Implement processes to procure highest priority data and hasten experimental progress
            • Update/Overhaul SPHINX to meet the broader needs of eMERGE III
            • Identify tools that need to be built for or included in DNA Nexus
            • Determine tools/metrics for functional annotation of variants
            • Include Structural Variants in final output


Chairpersons:  Laura Rasmussen-Torvik (Northwestern) & Cindy Prows (CCHMC)

The eMERGE PGx workgroup coordinates and promotes pharmacogenomic discovery and implementation work across the eMERGE consortium. In eMERGE 3, the PGx workgroup will collaborate with the other workgroups to:

              • Advise the clinical sequencing centers on optimal PGx report content and format
              • Understand the details of PGx variant return off the eMERGESeq platform across the eMERGE 3 sites
              • Promote network-wide investigation of drug response phenotypes
              • Coordinate continued analysis of implementation outcomes for the eMERGE 2 PGx supplement
              • Facilitate continued PGx variant discovery via the PGRNSeq, eMERGESeq, and eMERGE3 imputed GWAS datasets
              • Evaluate potential network wide PGx implementation projects using PGRNSeq and/or eMERGE3seq panel results


Chairpersons: Chunhua Weng (Columbia) & Wei-Qi Wei (VUMC)
The Phenotyping Workgroup carries out core functions in eMERGE III phenotyping and advances the science of phenotype development. Phenotyping is defined broadly, including not only case and control identification, but also cohort identification—with probability estimation and subtype determination—and the extraction of continuous features. The workgroup:

                • defines the process for generating phenotypes,
                • manages phenotype development, validation, and evaluation,
                • facilitates research into symbolic and numeric techniques like knowledge engineering and machine learning,
                • adopts or develops standards for phenotyping,
                • collaborates with other workgroups and outside stakeholders, and
                • disseminates the algorithms, tools, and results.


Chairpersons: Hakon Hakonarson (Children’s Hospital of Philadelphia), Josh Peterson (Vanderbilt), & Marc Williams (Geisinger)

The Outcomes workgroup will develop cross-site outcomes to track implementation and impact of eMERGE III sequencing. The workgroup will focus on answering the overarching question of whether eMERGE III-generated genomic results impact health care utilization and outcomes of importance to patients and families.

Outcomes will consist of specific process measures or health outcomes to determine impact:
Process outcomes:


                  • management of sequencing data at each site
                  • return of results process measures
                  • phenotype/genotype correlations
                  • changes in health care utilization associated with reported genomic variation
                  • clinician response measures

Health outcomes:

                    • intermediate outcomes (a biomarker or finding indicating future benefit or harm is more likely)
                    • clinical outcomes (the benefits or harms to a patient who receives an intervention)
                    • patient reported outcomes related to genetic susceptibility
                    • family reported outcomes related to genetic susceptibility

In the process of collecting outcomes, the workgroup will assess the impact of outcome differences on economic measures through a sub-workgroup. Additionally, the workgroup will assess the potential effect of reporting outcomes on health care policy.

Objectives for the workgroup:

                  • Define and prioritize eMERGE III outcomes and impact
                  • Develop a framework to guide outcome assessment at all sites
                  • Designate mandatory vs optional outcomes
                  • Develop a reporting mechanism and schedule
                  • Follow through on eMERGE PGx evaluation plans

Return of Results/ Ethical, Legal and Social Implications (ELSI)

Chairpersons: Ingrid Holm (Boston Children’s Hospital) & Iftikhar Kullo (Mayo)

The RoR/ELSI workgroup will determine actionability of annotated variants, process for the return of genomic results, and the impact of return of results on participants and patients, their families, health care providers, and health care systems.

                    • Develop and identify categories and thresholds of actionability. The Clinical Annotation Workgroup will assess individual variants in terms these categories and thresholds to individual variants.
                    • Assess ways to address the dynamic nature of genetic knowledge, i.e. potential change in risk as additional susceptibility variants are identified (with Clinical Annotation Workgroup).
                    • Review methods of governance including informed consent at sites and the role of participant and patient decision making in return of results
                    • Evaluate mechanisms of ROR at sites. Review commonalities and differences and establish standards, e.g. around how and when results are returned and what information is provided with the results
                    • Develop and assess reports, clinical decision support logic, and provider education (with EHRI WG)
                    • Review patient education and patient portals
                    • Assess the ethical, legal, and social implications of returning results in eMERGE III, in particular incorporation into the EHR
                    • Assess the impact of return of results on patients’ relationship with their health care providers
                    • Evaluate the psychosocial responses to the ROR, including the impact on participants and patients and their families (with Outcomes WG)
                    • Study the impact of data sharing on participant and patient privacy and confidentiality


In the News

Here's what's happening with eMerge:


Read the full press release here. Congratulations to all the sites in the next round of eMERGE! The new clinical sites will be led by: Iftikhar J. Kullo, M.D., at Mayo Clinic, Rochester, Minnesota Dan M. Roden, M.D., at Vanderbilt University Medical Center, Nashville, Tennessee Elizabeth W. Karlson, M.D., at Brigham and Women’s Hospital, Boston Rex […]


The eMERGE Network is excited to share that the MCS NT304, Predictive Utility of Polygenic Risk Scores for Coronary Heart Disease in the eMERGE Network; was published on May 7th to American Journal of Human Genetics.


Two companion RFAs for the PRS Diversity Consortium are now published: Polygenic Risk Score (PRS) Methods and Analysis for Populations of Diverse Ancestry – Study Sites (U01 Clinical Trial Not Allowed): Polygenic Risk Score (PRS) Methods and Analysis for Populations of Diverse Ancestry – Coordinating Center (U01 Clinical Trial Not Allowed): The goal […]


Notice to Encourage Eligible NHGRI Awardees to Apply for PA-18-906 “Research Supplements to Promote Diversity in Health-Related Research” PIs of active NHGRI research grants can apply; identify eligible individuals, including those from underrepresented groups, for support and mentorship under the auspices of this supplement opportunity. Supplement can support individuals from the undergraduate to the […]