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.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01HG006830-02S1
Application #
8714381
Study Section
Special Emphasis Panel (ZHG1-HGR-P (J2))
Program Officer
Li, Rongling
Project Start
2012-05-15
Project End
2015-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
2
Fiscal Year
2013
Total Cost
$200,047
Indirect Cost
$80,616
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Mortensen, Li J; Kreiner-Moller, Eskil; Hakonarson, Hakon et al. (2014) The PCDH1 gene and asthma in early childhood. Eur Respir J 43:792-800
Rasmussen, Luke V; Thompson, Will K; Pacheco, Jennifer A et al. (2014) Design patterns for the development of electronic health record-driven phenotype extraction algorithms. J Biomed Inform 51:280-6
Li, Yun R; Levine, John E; Hakonarson, Hakon et al. (2014) Making the genomic leap in HCT: application of second-generation sequencing to clinical advances in hematopoietic cell transplantation. Eur J Hum Genet 22:715-23
B√łnnelykke, Klaus; Sleiman, Patrick; Nielsen, Kasper et al. (2014) A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations. Nat Genet 46:51-5
Brothers, Kyle B; Lynch, John A; Aufox, Sharon A et al. (2014) Practical guidance on informed consent for pediatric participants in a biorepository. Mayo Clin Proc 89:1471-80
Cook-Sather, Scott D; Li, Jin; Goebel, Theodora K et al. (2014) TAOK3, a novel genome-wide association study locus associated with morphine requirement and postoperative pain in a retrospective pediatric day surgery population. Pain 155:1773-83
Matsunami, Nori; Hensel, Charles H; Baird, Lisa et al. (2014) Identification of rare DNA sequence variants in high-risk autism families and their prevalence in a large case/control population. Mol Autism 5:5
Sleiman, Patrick M A; Wang, Mei-Lun; Cianferoni, Antonella et al. (2014) GWAS identifies four novel eosinophilic esophagitis loci. Nat Commun 5:5593
Rasmussen-Torvik, L J; Stallings, S C; Gordon, A S et al. (2014) Design and anticipated outcomes of the eMERGE-PGx project: a multicenter pilot for preemptive pharmacogenomics in electronic health record systems. Clin Pharmacol Ther 96:482-9
Keller, M; Glessner, J; Resnick, E et al. (2014) Burden of copy number variation in common variable immunodeficiency. Clin Exp Immunol 177:269-71

Showing the most recent 10 out of 12 publications