• Two genome wide significant loci were found in Asthma. There is a genome wide signal in African Americans with GERD, and CHOP is still pursuing this replication. Four genes replicated from the pediatric Atopic dermatitis dataset. Three SNPs reached genome wide significance in ADHD and have been replicated. • PGx: recruitment is completed with 1,650 children from CAG’s biorepository with well-documented drug related severe adverse events and EHR-based drug response profiles. Significant p-values were found in both analyses of African Americans and European Americans comparing severe asthma v. not severe. • Return of Results: 440 results were returned as of 6/26 and a projected 1,500 will be returned by 8/1/2015. Myresults.org was integrated into the EHR. Early-onset, severe forms of ‘essential’ hypertension and major cardiovascular complications of hypertension are associated with Apolipoprotein L1 (APOL1) renal risk alleles in African Americans - Girish N Nadkarni & Geneviève Galarneau • APOL1 gene variants associate with increased ranges of blood pressure (both systolic and diastolic) in younger African Americans (under age 40) independent of estimated glomerular filtration rate. • The combined cohort of 9,203 participants across eMERGE led to 1345/14.6% with APOL1 risk status. • APOL1 risk allele is associated with 2.4 Years earlier diagnosis of hypertension. Higher blood pressures were found in 20-39 years. • 2 APOL1 risk alleles were also associated with a higher rate of left ventricular hypertrophy and hemorrhagic stroke, complications of hypertension. After preforming a logistic regression that adjusted for age, sex and BMI, there were significant odds ratios of 1.52 and 2.66 respectively. • The results may warrant a paradigm shift from a kidney-intrinsic to systemic vascular pathomechanism(s) for APOL1 risk alleles. The results may also have considerable public health implications for BP screening in young AA carrying APOL1 risk alleles. Mayo Site Update – Iftikhar Kullo • Mayo has implemented eight phenotypes and lists the following as phenotype highlights: harmonized phenotype data dictionaries across the consortium, aligned eMERGE with PhenX, and developed the eleMAP tool, open- source NLP resource cTAKES, and PhEMA. • Genomics: Performed the QC for the network wide high-density genotype dataset for dbGaP submission, completing the GWAS of VTE, HF, and CRF, activity in genetic risk score research, structural and null variant projects, PheWAS projects, and the ENCODE collaboration. Mayo looks to replicate findings in the African American VTE cohort, CF, and HF. • Return of Results: Mayo’s primary return of results work focused on the MIGENES clinical trial. The site was also involved in MyResults.org, the RoR instruments repository, manuscripts describing RoR activities in the Network, the PGx consent form, the RoR template for PGx actionable events, and larger contributions to Network wide projects, such as HFE. • The MIGENES trial illustrates the feasibility of incorporating genomic risk information for common disease into the EHR. A risk report was placed in the EHR and a decision aid tool was also embedded into the EHR. Disclosing of CHD led to lower LDL cholesterol levels and increased information seeking and sharing amongst the physicians and patients. • Mayo has participated in several CERC and CERC Survey committees, including co-chairing the IRB committee in CERC Survey. eMERGE members at Mayo have also led the patient and provider PGx education surveys and participated in CERC/CSER and CERC/RoR papers. • EHRI: Mayo shared their EHR-based genomic decision aid to facilitate shared decision making after the disclosure of CHD. They contributed to the development of the InfoButton resource for PGx CDS and shared their CDS logic for simvastatin, clopidogrel, and warfarin.