The eMERGE genotype set of 83,717 subjects imputed to ~40 million variants genome wide and association with the herpes zoster medical record phenotype

The eMERGE Network

doi:10.1002/gepi.22167

The eMERGE genotype set of 83,717 subjects imputed to ~40 million variants genome wide and association with the herpes zoster medical record phenotype

The eMERGE Network

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

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 (US)
Pages (from-to)	63-81
Number of pages	19
Journal	Genetic Epidemiology
Volume	43
Issue number	1
DOIs	https://doi.org/10.1002/gepi.22167
State	Published - Feb 2019

Funding

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. 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.

Keywords

GWAS
electronic medical records
genotypes
herpes zoster
variants

ASJC Scopus subject areas

Epidemiology
Genetics(clinical)

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10.1002/gepi.22167

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title = "The eMERGE genotype set of 83,717 subjects imputed to ~40 million variants genome wide and association with the herpes zoster medical record phenotype",

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).",

keywords = "GWAS, electronic medical records, genotypes, herpes zoster, variants",

author = "{The eMERGE Network} and Stanaway, {Ian B.} and Hall, {Taryn O.} and Rosenthal, {Elisabeth A.} and Melody Palmer and Vivek Naranbhai and Rachel Knevel and Bahram Namjou-Khales and Carroll, {Robert J.} and Krzysztof Kiryluk and Gordon, {Adam Samuel} and Jodell Linder and Howell, {Kayla Marie} and Mapes, {Brandy M.} and Lin, {Frederick T.J.} and Joo, {Yoonjung Yoonie} and Hayes, {M Geoffrey} and Gharavi, {Ali G.} and Pendergrass, {Sarah A.} and Ritchie, {Marylyn D.} and {de Andrade}, Mariza and Croteau-Chonka, {Damien C.} and Soumya Raychaudhuri and Weiss, {Scott T.} and Matt Lebo and Amr, {Sami S.} and David Carrell and Larson, {Eric B.} and Chute, {Christopher G.} and Rasmussen-Torvik, {Laura Jarmila} and Roy-Puckelwartz, {Megan J.} and Patrick Sleiman and Hakon Hakonarson and Rongling Li and Karlson, {Elizabeth W.} and Peterson, {Josh F.} and Kullo, {Iftikhar J.} and Chisholm, {Rex L} and Denny, {Joshua Charles} and Jarvik, {Gail P.} and Crosslin, {David R.}",

note = "Publisher Copyright: {\textcopyright} 2018 The Authors. Genetic Epidemiology Published by Wiley Periodicals, Inc.",

year = "2019",

month = feb,

doi = "10.1002/gepi.22167",

language = "English (US)",

volume = "43",

pages = "63--81",

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AU - The eMERGE Network

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 Samuel

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 L

AU - Denny, Joshua Charles

AU - Jarvik, Gail P.

AU - Crosslin, David R.

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KW - variants

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The eMERGE genotype set of 83,717 subjects imputed to ~40 million variants genome wide and association with the herpes zoster medical record phenotype

Abstract

Funding

Keywords

ASJC Scopus subject areas

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