The Center for Applied Genomics (CAG) at The Children's Hospital of Philadelphia (CHOP) has established a pediatric biorepository with over 40,000 children who have been consented for access to electronic medical records (EMRs) with updates and recontact. All of the study subjects have been genotyped on either the Infinium 550HH, 610Q, 660Q (Illumina) or the Affymetrix 6.0 genome-wide association study (GWAS) arrays. NHGRI initiated the electronic medical records and genomics (eMERGE) Network in 2007 to support existing biorepositories to develop necessary methods and procedures to facilitate GWAS in participants with phenotypes and environmental exposures derived from EMRs. This effort was recently expanded and is now incorporating Pediatric Study Investigators (PSI) with existing biorepositories. Our CAG center is extremely well positioned for this opportunity given its large-scale dataset and resources we have built. Our primary objective is to build upon the eMERGE initiatives and define phenotypes from EMRs in accordance with eMERGE procedures and conduct GWAS with minimal risks to patient privacy from sharing of EMR data, and develop consent and community consultation procedures for conduct of research and begin incorporating genomic research results into clinical care. We will achieve these goals in collaboration with the other eMERGE network groups and the NHGRI to expand and incorporate new phenotypes with the intention of incorporating GWA genotyping information into EMRs in an attempt to improve clinical care. Specifically, in Specific Aim 1, we will use EMRs from >40,000 children of all ethnic groups, aged 0-21, already genotyped on dense GWAS arrays, to mine disease phenotypes and environmental exposure data in over 40 phenotypes and establish a phenotype/genotype database for future clinical development with other eMERGE sites. We will also mine EMR data to determine pharmacogenetic (PGx) response profiles, both efficacy and adverse events and search for polymorphisms impacting variation in response to commonly used drugs in the existing pediatric dataset.
In Specific Aim 2, we will extend our CLIA/CAP certified workflow status in our array-based clinical cytogenomics program to enable future sharing of genetic/genomic data with the study participants.
In Specific Aim 3, we will establish guidelines &governance rules for the CAG biorepository and databases in keeping with eMERGE sites, and generate informed consent procedures that optimize existing data and sample use for research and foster clinical utility of the data in collaboration with the other eMERGE groups. All CHOP patients are on EMR and we have invested significantly in integrating EMR and GWAS datasets and incorporating the outputs into our certified to CAP/CLIA standards, in keeping with the objectives of the eMERGE program. Thus, we believe CAG is exceptionally well positioned to contribute to the eMERGE-II Pediatric network.

Public Health Relevance

National programs integrating GWAS data with Electronic Medical Records (EMRs) such as the eMERGE programs, present a powerful approach for integrative data analysis across multiple study sites, addressing key feasibly issues for phenotype-genotype correlations. We propose to use EMRs from >40,000 children, aged 0-21, already genotyped on dense GWAS arrays, to mine disease phenotypes and environmental exposure data in as many as 40 disease areas. We will additionally examine pharmacogenomic traits of both response and adverse events and establish workflows for array-based research that allow for sharing of genetic/genomic data with the study participants and we will work collaboratively to establish guidelines &governance rules for biorepositories and databases to foster future clinical utility of the data.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZHG1-HGR-P (J2))
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Li, Rongling
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Children's Hospital of Philadelphia
United States
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van Ingen, Gijs; Li, Jin; Goedegebure, André et al. (2016) Genome-wide association study for acute otitis media in children identifies FNDC1 as disease contributing gene. Nat Commun 7:12792
Verma, Anurag; Verma, Shefali S; Pendergrass, Sarah A et al. (2016) eMERGE Phenome-Wide Association Study (PheWAS) identifies clinical associations and pleiotropy for stop-gain variants. BMC Med Genomics 9 Suppl 1:32
Finkel, Terri H; Li, Jin; Wei, Zhi et al. (2016) Variants in CXCR4 associate with juvenile idiopathic arthritis susceptibility. BMC Med Genet 17:24
Lingren, Todd; Chen, Pei; Bochenek, Joseph et al. (2016) Electronic Health Record Based Algorithm to Identify Patients with Autism Spectrum Disorder. PLoS One 11:e0159621
Rasmussen, Luke V; Overby, Casey L; Connolly, John et al. (2016) Practical considerations for implementing genomic information resources. Experiences from eMERGE and CSER. Appl Clin Inform 7:870-82
Garrison, Nanibaa' A; Sathe, Nila A; Antommaria, Armand H Matheny et al. (2016) A systematic literature review of individuals' perspectives on broad consent and data sharing in the United States. Genet Med 18:663-71
Satterthwaite, Theodore D; Connolly, John J; Ruparel, Kosha et al. (2016) The Philadelphia Neurodevelopmental Cohort: A publicly available resource for the study of normal and abnormal brain development in youth. Neuroimage 124:1115-9
Van Driest, Sara L; Wells, Quinn S; Stallings, Sarah et al. (2016) Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records. JAMA 315:47-57
Smith, Maureen E; Sanderson, Saskia C; Brothers, Kyle B et al. (2016) Conducting a large, multi-site survey about patients' views on broad consent: challenges and solutions. BMC Med Res Methodol 16:162
Desai, Akshatha; Connolly, John J; March, Michael et al. (2016) Systematic data-querying of large pediatric biorepository identifies novel Ehlers-Danlos Syndrome variant. BMC Musculoskelet Disord 17:80

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