• A chart review validation tool was created that allows data capture in a structured way, which eases the creation of training and validation data sets. Two other eMERGE sites are also using this tool and the related KNIME workflow. • A GWAS of diverticulosis showed near genome wide significance, using nearly 5,000 European American cases. A GWAS comparing African American diverticulosis v. diverticulitis was completed and shows an odds ratio of .36, which NU will follow up. NU colon polyp research found a 94% PPV for cases, 98% PPV for controls, looking at over 10,000 colonoscopies across 6 eMERGE sites. NU tried to find “gold” and “silver” standard caMRSA definitions in the EHR, but such proved difficult. The numbers were small, but the GWAS finding shows significant hits in the HLA region. • Fluomics project looks to return exomes to the eMERGE sites. The next step is sequence the remaining samples. • NU physicians decided they wanted all results and NU has worked closely with the physicians through an advisory committee. A patient advisory committee was also created to ease communication between the patient and physician. Genetic results are implemented into the EHR through an Ancillary Genomic System and there is a patient portal as well, so both groups are interacting with the data. • Return of Results: Genomic Medicine Project: 29 NU patients have received results (7 carriers – 6 HH, 1 PT) and all the results are in the EHR with BPA firing. They then compared CLIA results with GWAS for 19 participants and found a discordance for 2 participants who are heterozygous for PT mutation. PGx: 750 NU patients enrolled, pre & post studies were sent to all the patients, and so far, 450 patients received results. Results will continue to be returned over the next 5 weeks. • A shortened consent v. standard length consent study showed no statistical differences in objective or subjective comprehension. Homozygous Deletions in eMERGE – Joseph Glessner • A pipeline was established for copy number variant (CNV) calling, sample QC, association analysis, and further CNVR QC. • CNV calls were identified by PennCNV, which implements a hidden Markov model algorithm. Associations between CNVs and diseases/traits were identified by ParseCNV and PLINK. • A total of 560 homozygous deletion regions were identified, which may affect the gene structure. Of those, 146 were found in multiple individuals and 57 were significantly enriched for a broad category of phenotypes including autoimmune, cancers, cardiovascular, healthy and neurological diseases. • Harvey Weinberg Equilibrium and large CNV filtering are crucial extra quality controls for this data. Discussion after the presentation suggested using age as a co-variant. Mount Sinai Site Report – Erwin Bottinger • BioMe, Mount Sinai’s biobank, is ancestrally diverse. Notably, 40% of the white population is Ashkenazi Jewish, and the majority of Hispanic population is Caribbean. BioMe has allowed participation in nearly all major genetic consortia. Ashkenazi Jews in the biobank have the highest level of genome sharing, at 3%. Three different rare variants have been linked with the EHR. • CLIPMERGE platform interacts with EMR bio-directional and in real time, providing CDS to the physicians. • Mount Sinai has contributed over 40,000 cases and controls to eMERGE phenotype data. Mount Sinai phenotypes focused on kidney and liver (Columbia) diseases. • CKD: validated by Columbia and Marshfield. Combined reduced kidney function & CKD yielded over 20,000 instances. Analysis is underway using a population control instead of the standard case control. The development and validation of the CKD algorithm won the 2014 AMIA distinguished paper award. AKI: preparing algorithm development paper, but unable to do genetic analyses. • Mount Sinai has developed machine learning tools for advanced phenotyping to cluster longitudinal kidney data. They have also incorporated temporal EHR data in predictive models for risk stratification of renal function.