• There is real opportunity in leveraging patient-reported data along with EHR data to improve association analyses and understand population effects. Also to use this data combination to study intervention effectiveness. • eMERGE would focus on incorporating more on patient-reported data, not so much comparative effectiveness analysis. • Comparative analysis is slippery slope. We don’t know enough about whole genome vs. targeted yet to make that kind of comparison. An uninformed trial could damage the field. • PCORI funds methodology development, so eMERGE could perhaps co-fund a methodology development project through PCORI. Central Phenotype Dataset Discussion - Group • NHGRI inquired with the group as to whether there was utility in having a phenotype dataset for the Network. A large dbGaP set including the main study is already available, but only includes case/control status. The phenotype association study data would likely be needed as well, but it’s being submitted in a secondary round, and kept separately. • The CC will draft a dataset proposal to circulate to PIs for feedback. ACTION ITEM: The CC will draft a central phenotype dataset proposal to circulate to PIs.
Day 2: Half-day Session
Return of Results Update – Gail Jarvik & Iftikhar Kullo • The workgroup cites their work on GRS/variants for complex disease risk, phenotypic correlates of Variants of Unknown Significance, HFE variants, pathogenicity, penetrance, and actionability as accomplishments. Additionally, return of results linkage to CDS, interactions & collaborations with other groups (CERC, CSER, AIG), along with 13 eMERGE RoR abstracts presented at ASHG in 2014 and the CSER collaboration paper reflect the group’s productivity. • Reflecting eMERGE II’s emphasis on implementation, the flagship genomic medicine projects, ranging from genetic risk scores, SNPs, WGS, and to PGx have proved successful. • The process of returning actionable variants is not trivial. Both MyResults.org portal and the recently created return of results web resource have allowed for standardized collection across sites. CDS at point of care has also led to collaborations within eMERGE through discussions and tools. • The workgroup actively discussed the FDA regulation of genomic tests. Many eMERGE members endorsed comments submitted by Barbara Evans and Gail Jarvik. • In closing out eMERGE II, the workgroup has discussed two Network papers: 1. Site specific response to the high penetrance response and 2. Return of PGx variants across the Network. The workgroup also plans to complete Network wide projects (HFE penetrance, RoR in eMERGE PGx), leverage the EHR for variant annotation, link EHR-based RoR to CDS, assist ClinVar pathogenicity submissions, follow and respond to FDA regulation of genomic testing, and continue collaborations across NHGRI and other genomic programs, including interactions with CSER, INGNITE, and CLINGEN. ACTION ITEM: Members interested in leading the two proposed Network proposed RoR papers should contact Gail Jarvik & Iftikhar Kullo. Northwestern Site Update – Rex Chisholm & Maureen Smith • Northwestern’s phenotype analysis focused on a lower GI case & control study flow, focusing on cases with colon polyps, diverticulitis, or diverticulosis. A natural language processing pipeline was developed and allowed generation of clinical quality metrics.