Abstract
The Electronic Medical Records and Genomics (eMERGE) network is a network of medical centers with electronic medical records linked to existing biorepository samples for genomic discovery and genomic medicine research. The network sought to unify the genetic results from 78 Illumina and Affymetrix genotype array batches from 12 contributing medical centers for joint association analysis of 83,717 human participants. In this report, we describe the imputation of eMERGE results and methods to create the unified imputed merged set of genome-wide variant genotype data. We imputed the data using the Michigan Imputation Server, which provides a missing single-nucleotide variant genotype imputation service using the minimac3 imputation algorithm with the Haplotype Reference Consortium genotype reference set. We describe the quality control and filtering steps used in the generation of this data set and suggest generalizable quality thresholds for imputation and phenotype association studies. To test the merged imputed genotype set, we replicated a previously reported chromosome 6 HLA-B herpes zoster (shingles) association and discovered a novel zoster-associated loci in an epigenetic binding site near the terminus of chromosome 3 (3p29).
Original language | English |
---|---|
Pages (from-to) | 63-81 |
Number of pages | 19 |
Journal | Genetic Epidemiology |
Volume | 43 |
Issue number | 1 |
Publication status | Published - Feb 2019 |
Externally published | Yes |
Keywords
- electronic medical records
- genotypes
- GWAS
- herpes zoster
- variants
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In: Genetic Epidemiology, Vol. 43, No. 1, 02.2019, p. 63-81.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - The eMERGE genotype set of 83,717 subjects imputed to ~40 million variants genome wide and association with the herpes zoster medical record phenotype
AU - Stanaway, Ian B.
AU - Hall, Taryn O.
AU - Rosenthal, Elisabeth A.
AU - Palmer, Melody
AU - Naranbhai, Vivek
AU - Knevel, Rachel
AU - Namjou-Khales, Bahram
AU - Carroll, Robert J.
AU - Kiryluk, Krzysztof
AU - Gordon, Adam S.
AU - Linder, Jodell
AU - Howell, Kayla Marie
AU - Mapes, Brandy M.
AU - Lin, Frederick T.J.
AU - Joo, Yoonjung Yoonie
AU - Hayes, M. Geoffrey
AU - Gharavi, Ali G.
AU - Pendergrass, Sarah A.
AU - Ritchie, Marylyn D.
AU - de Andrade, Mariza
AU - Croteau-Chonka, Damien C.
AU - Raychaudhuri, Soumya
AU - Weiss, Scott T.
AU - Lebo, Matt
AU - Amr, Sami S.
AU - Carrell, David
AU - Larson, Eric B.
AU - Chute, Christopher G.
AU - Rasmussen-Torvik, Laura Jarmila
AU - Roy-Puckelwartz, Megan J.
AU - Sleiman, Patrick
AU - Hakonarson, Hakon
AU - Li, Rongling
AU - Karlson, Elizabeth W.
AU - Peterson, Josh F.
AU - Kullo, Iftikhar J.
AU - Chisholm, Rex
AU - Denny, Joshua Charles
AU - Jarvik, Gail P.
AU - The eMERGE Network
AU - Crosslin, David R.
N1 - Funding Information: In eMERGE network (Phase 3 ascertainment), this phase of the eMERGE Network was initiated and funded by the NHGRI through the following grants: U01HG8657 (Kaiser Washington/University of Washington); U01HG8685 (Brigham and Women’s Hospital); U01HG8672 (Vanderbilt University Medical Center); U01HG8666 (Cincinnati Children’s Hospital Medical Center); U01HG6379 (Mayo Clinic); U01HG8679 (Geisinger Clinic); U01HG8680 (Columbia University Health Sciences); U01HG8684 (Children’s Hospital of Philadelphia); U01HG8673 (Northwestern University); U01HG8701 (Vanderbilt University Medical Center serving as the Coordinating Center); U01HG8676 (Partners Healthcare/Broad Institute); and U01HG8664 (Baylor College of Medicine). In eMERGE network (Phase 1 and 2 ascertainment), the eMERGE Network was initiated and funded by NHGRI through the following grants: U01HG006828 (Cincinnati Children’s Hospital Medical Center/Boston Children’s Hospital); U01HG006830 (Children’s Hospital of Philadelphia); U01HG006389 (Essentia Institute of Rural Health, Marshfield Clinic Research Foundation and Pennsylvania State University); U01HG006382 (Geisinger Clinic); U01HG006375 (Group Health Cooperative/University of Washington); U01HG006379 (Mayo Clinic); U01HG006380 (Icahn School of Medicine at Mount Sinai); U01HG006388 (Northwestern University); U01HG006378 (Vanderbilt University Medical Center); and U01HG006385 (Vanderbilt University Medical Center serving as the Coordinating Center) with U01HG004438 (CIDR) and U01HG004424 (the Broad Institute) serving as Genotyping Centers. Funding Information: In eMERGE network (Phase 3 ascertainment), this phase of the eMERGE Network was initiated and funded by the NHGRI through the following grants: U01HG8657 (Kaiser Washington/University of Washington); U01HG8685 (Brigham and Women?s Hospital); U01HG8672 (Vanderbilt University Medical Center); U01HG8666 (Cincinnati Children?s Hospital Medical Center); U01HG6379 (Mayo Clinic); U01HG8679 (Geisinger Clinic); U01HG8680 (Columbia University Health Sciences); U01HG8684 (Children?s Hospital of Philadelphia); U01HG8673 (Northwestern University); U01HG8701 (Vanderbilt University Medical Center serving as the Coordinating Center); U01HG8676 (Partners Healthcare/Broad Institute); and U01HG8664 (Baylor College of Medicine). In eMERGE network (Phase 1 and 2 ascertainment), the eMERGE Network was initiated and funded by NHGRI through the following grants: U01HG006828 (Cincinnati Children?s Hospital Medical Center/Boston Children?s Hospital); U01HG006830 (Children?s Hospital of Philadelphia); U01HG006389 (Essentia Institute of Rural Health, Marshfield Clinic Research Foundation and Pennsylvania State University); U01HG006382 (Geisinger Clinic); U01HG006375 (Group Health Cooperative/University of Washington); U01HG006379 (Mayo Clinic); U01HG006380 (Icahn School of Medicine at Mount Sinai); U01HG006388 (Northwestern University); U01HG006378 (Vanderbilt University Medical Center); and U01HG006385 (Vanderbilt University Medical Center serving as the Coordinating Center) with U01HG004438 (CIDR) and U01HG004424 (the Broad Institute) serving as Genotyping Centers. Publisher Copyright: © 2018 The Authors. Genetic Epidemiology Published by Wiley Periodicals, Inc.
PY - 2019/2
Y1 - 2019/2
N2 - The Electronic Medical Records and Genomics (eMERGE) network is a network of medical centers with electronic medical records linked to existing biorepository samples for genomic discovery and genomic medicine research. The network sought to unify the genetic results from 78 Illumina and Affymetrix genotype array batches from 12 contributing medical centers for joint association analysis of 83,717 human participants. In this report, we describe the imputation of eMERGE results and methods to create the unified imputed merged set of genome-wide variant genotype data. We imputed the data using the Michigan Imputation Server, which provides a missing single-nucleotide variant genotype imputation service using the minimac3 imputation algorithm with the Haplotype Reference Consortium genotype reference set. We describe the quality control and filtering steps used in the generation of this data set and suggest generalizable quality thresholds for imputation and phenotype association studies. To test the merged imputed genotype set, we replicated a previously reported chromosome 6 HLA-B herpes zoster (shingles) association and discovered a novel zoster-associated loci in an epigenetic binding site near the terminus of chromosome 3 (3p29).
AB - The Electronic Medical Records and Genomics (eMERGE) network is a network of medical centers with electronic medical records linked to existing biorepository samples for genomic discovery and genomic medicine research. The network sought to unify the genetic results from 78 Illumina and Affymetrix genotype array batches from 12 contributing medical centers for joint association analysis of 83,717 human participants. In this report, we describe the imputation of eMERGE results and methods to create the unified imputed merged set of genome-wide variant genotype data. We imputed the data using the Michigan Imputation Server, which provides a missing single-nucleotide variant genotype imputation service using the minimac3 imputation algorithm with the Haplotype Reference Consortium genotype reference set. We describe the quality control and filtering steps used in the generation of this data set and suggest generalizable quality thresholds for imputation and phenotype association studies. To test the merged imputed genotype set, we replicated a previously reported chromosome 6 HLA-B herpes zoster (shingles) association and discovered a novel zoster-associated loci in an epigenetic binding site near the terminus of chromosome 3 (3p29).
KW - electronic medical records
KW - genotypes
KW - GWAS
KW - herpes zoster
KW - variants
UR - http://www.scopus.com/inward/record.url?scp=85054579060&partnerID=8YFLogxK
M3 - Article
C2 - 30298529
AN - SCOPUS:85054579060
SN - 0741-0395
VL - 43
SP - 63
EP - 81
JO - Genetic Epidemiology
JF - Genetic Epidemiology
IS - 1
ER -