title: Imputation and quality control steps for combining multiple genome-wide datasets.
abstract: The electronic MEdical Records and GEnomics (eMERGE) network brings together DNA biobanks linked to electronic health records (EHRs) from multiple institutions. Approximately 51,000 DNA samples from distinct individuals have been genotyped using genome-wide SNP arrays across the nine sites of the network. The eMERGE Coordinating Center and the Genomics Workgroup developed a pipeline to impute and merge genomic data across the different SNP arrays to maximize sample size and power to detect associations with a variety of clinical endpoints. The 1000 Genomes cosmopolitan reference panel was used for imputation. Imputation results were evaluated using the following metrics: accuracy of imputation, allelic R (2) (estimated correlation between the imputed and true genotypes), and the relationship between allelic R (2) and minor allele frequency. Computation time and memory resources required by two different software packages (BEAGLE and IMPUTE2) were also evaluated. A number of challenges were encountered due to the complexity of using two different imputation software packages, multiple ancestral populations, and many different genotyping platforms. We present lessons learned and describe the pipeline implemented here to impute and merge genomic data sets. The eMERGE imputed dataset will serve as a valuable resource for discovery, leveraging the clinical data that can be mined from the EHR.
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Systems Genomics, The Pennsylvania State University Pennsylvania, PA, USA.
authors.forename: Shefali S
authors.initials: SS
authors.lastname: Verma
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic Rochester, MN, USA.
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.affiliation: The Sigfried and Janet Weis Center for Research, Geisinger Health System Danville, PA, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp
authors.affiliation: The Sigfried and Janet Weis Center for Research, Geisinger Health System Danville, PA, USA.
authors.forename: Helena
authors.initials: H
authors.lastname: Kuivaniemi
authors.affiliation: Center for Inherited Disease Research, John Hopkins University Baltimore, MD, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pugh
authors.affiliation: Cincinnati Children's Hospital Medical Center Cincinnati, OH, USA.
authors.forename: Bahram
authors.initials: B
authors.lastname: Namjou-Khales
authors.affiliation: Department of Medicine, University of Washington Seattle, WA, USA.
authors.forename: Shubhabrata
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Medicine, University of Washington Seattle, WA, USA.
authors.forename: Gail P
authors.initials: GP
authors.lastname: Jarvik
authors.affiliation: Cincinnati Children's Hospital Medical Center Cincinnati, OH, USA.
authors.forename: Leah C
authors.initials: LC
authors.lastname: Kottyan
authors.affiliation: Department of Medicine, University of Washington Seattle, WA, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Burt
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Systems Genomics, The Pennsylvania State University Pennsylvania, PA, USA.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Bradford
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Systems Genomics, The Pennsylvania State University Pennsylvania, PA, USA.
authors.forename: Gretta D
authors.initials: GD
authors.lastname: Armstrong
authors.affiliation: The Sigfried and Janet Weis Center for Research, Geisinger Health System Danville, PA, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Derr
authors.affiliation: Center for Human Genetics Research, Vanderbilt University Nashville, TN, USA ; Department of Epidemiology and Biostatistics, Case Western University Cleveland, OH, USA.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western University Cleveland, OH, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.affiliation: Division of Genomic Medicine, National Human Genome Research Institute Bethesda, MD, USA.
authors.forename: Rongling
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Washington Seattle, WA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Crosslin
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Systems Genomics, The Pennsylvania State University Pennsylvania, PA, USA.
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
keywords: eMERGE; electronic health records; genome-wide association; imputation