• Since Sept. 2010, 14,734 Vanderbilt patients have had PREDICT testing. Additionally, the PREDICT provider survey is complete and had a 56% response rate. Findings: 92% of clinicians favor immediate, active notification when significant drug-genome interaction is present. • Vanderbilt’s contribution to eMERGE II Phenotypes was also reviewed. VU led 4 phenotype algorithm validations (ACE-I Cough, MACE-Statins, BPH, and fibroids), and also provided secondary validation for 7 additional phenotypes. • The large scale replication of GWAS association results using PheWAS was reviewed. 3,000 SNPS were mapped. 751 phenotype associations were tested, 210 were replicated, 66% were adequately powered. Also discovered 63 new associations (mostly w/ skin phenotypes). • Results of the Neanderthal PheWAS found that 1.5% of the genome of non-African individuals is inherited from admixture with Neanderthals. Neanderthal alleles are identified in the eMERGE imputed set. Geisinger Site Report – David Carey & Marc Williams • Geisinger presented their site report as a ‘lessons learned,’ since their participation in eMERGE contributed to fundamental changes in their initial research approach. Two high level recommendations are: Adopt a concept of an enterprise wide Learning Health System. o Embrace engagementengagement of and partnership with Geisinger patients. o • Integrated health leveraged as platform for genomics research. This has caused Geisinger to think more aggressively about how to accelerate the return of information back to patients/providers to improve clinical care. • IT governance has changed, reorganization of informatics structure due to eMERGE processes. Comprehensive Review of Infobutton Project Project – John Connolly, Casey Overby, & Luke Rasmussen • The project aimed to develop new information resources based on eMERGE II and PGx scenarios, as well as implementing infobuttons within EHRs at eMERGE institutions. • A simulation study of 22 physicians using 3 prescribing scenarios from UW was provided. The resources were utilized by physicians: lab reviews were accessed 98 times, while the medication order entry context was accessed 74 times. • eMERGE sites are considering similar PGx scenarios (clopidogrel, warfarin, simvastatin). • Practical considerations were reviewed. Major considerations include ‘how content is developed,’ ‘where content is hosted’ (locally hosted content is preferred), ‘a mix of site-specific and general content is required.’ • Myresults.org was reviewed. An end-user evaluation is under way to gather perceptions of eMERGE-developed content. 18 surveys have been submitted at this point from eMERGE sites and collaborating institutions. • The project will continue developing during eMERGE Phase III. Marshfield/Essentia/PSU Site Report – Murray Brilliant, Catherine McCarty, & Marylyn Ritchie • Site phenotype work was presented. Algorithms were developed and validated for Ocular Hypertension, Glaucoma, and AMD. They also assisted in the validation of 32 network algorithms (16 being the primary or secondary validator). A machine learning phenotyping article was published in the Journal of Biomedical Informatics o (‘Relational Machine Learning for Electronic Health Record-driven Phenotyping’) • The site leveraged GWAS data available for ~6,000 research subjects at Marshfield and ~23,000 additional subjects across eMERGE to undertake discoveries for ophthalmic conditions and pharmacogenetics. 10,538 samples were available after QC. ‘Biology-driven Gene-Gene Interaction Analysis of Age-Related Cataract in the eMERGE Network’ was o published in Genetic Epidemiology. eMERGE-PCORnet Discussion - Group • NHGRI asked the group to identify avenues for collaboration with PCORI.