title: Cell Specific eQTL Analysis without Sorting Cells.
abstract: The functional consequences of trait associated SNPs are often investigated using expression quantitative trait locus (eQTL) mapping. While trait-associated variants may operate in a cell-type specific manner, eQTL datasets for such cell-types may not always be available. We performed a genome-environment interaction (GxE) meta-analysis on data from 5,683 samples to infer the cell type specificity of whole blood cis-eQTLs. We demonstrate that this method is able to predict neutrophil and lymphocyte specific cis-eQTLs and replicate these predictions in independent cell-type specific datasets. Finally, we show that SNPs associated with Crohn's disease preferentially affect gene expression within neutrophils, including the archetypal NOD2 locus.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Harm-Jan
authors.initials: HJ
authors.lastname: Westra
authors.affiliation: Groningen Bioinformatics Centre, University of Groningen, Groningen, The Netherlands.
authors.forename: Danny
authors.initials: D
authors.lastname: Arends
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia; Divisions of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, United States of America; Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America; Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Tõnu
authors.initials: T
authors.lastname: Esko
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre Rotterdam, the Netherlands; The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden/ Rotterdam, the Netherlands.
authors.forename: Marjolein J
authors.initials: MJ
authors.lastname: Peters
authors.affiliation: Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany; The Charles Bronfman Institute for Personalized Medicine, Genetics of Obesity & Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schurmann
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institut für Humangenetik, Technische Universität München, München, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schramm
authors.affiliation: Computational Medicine, Institute of Health Sciences, Faculty of Medicine, University of Oulu, Oulu, Finland; Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland; Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kettunen
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
authors.forename: Hanieh
authors.initials: H
authors.lastname: Yaghootkar
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom; Department of Oncology, Cancer and Haematology Centre, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Fairfax
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Anand Kumar
authors.initials: AK
authors.lastname: Andiappan
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands; Groningen Bioinformatics Centre, University of Groningen, Groningen, The Netherlands.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Fu
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Juha
authors.initials: J
authors.lastname: Karjalainen
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Platteel
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands.
authors.forename: Marijn
authors.initials: M
authors.lastname: Visschedijk
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands.
authors.forename: Rinse K
authors.initials: RK
authors.lastname: Weersma
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Silva
authors.initials: S
authors.lastname: Kasela
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Lili
authors.initials: L
authors.lastname: Milani
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
authors.forename: Liina
authors.initials: L
authors.lastname: Tserel
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
authors.forename: Pärt
authors.initials: P
authors.lastname: Peterson
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Eva
authors.initials: E
authors.lastname: Reinmaa
authors.affiliation: The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden/ Rotterdam, the Netherlands; Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre Rotterdam, the Netherlands; The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden/ Rotterdam, the Netherlands; Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre Rotterdam, the Netherlands; The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden/ Rotterdam, the Netherlands; Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.affiliation: Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Astrid
authors.initials: A
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authors.affiliation: Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Roberto
authors.initials: R
authors.lastname: Lorbeer
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institut für Humangenetik, Technische Universität München, München, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institut für Humangenetik, Technische Universität München, München, Germany; Munich Heart Alliance, Munich, Germany; German Center for Cardiovascular Research (DZHK), Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research (DZD), partner site Düsseldorf, Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research (DZD), partner site Düsseldorf, Düsseldorf, Germany; Department of Diabetology and Endocrinology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.affiliation: Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland; Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland; Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom; Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia; Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Wood
authors.affiliation: Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Melzer
authors.affiliation: Clinical Research Branch, National Institute on Aging NIA-ASTRA Unit, Harbor Hospital, Baltimore, Maryland, United States of America.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America; Department of Molecular Neuroscience and Reta Lila Laboratories, Institute of Neurology, UCL, London, United Kingdom.
authors.forename: Dena G
authors.initials: DG
authors.lastname: Hernandez
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: Julian C
authors.initials: JC
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authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore; Doctoral School in Translational and Molecular Medicine (DIMET), University of Milano-Bicocca, Milan, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Melchiotti
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Bernett
authors.initials: B
authors.lastname: Lee
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zolezzi
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Anis
authors.initials: A
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authors.affiliation: Department of Otolaryngology, National University of Singapore, Singapore.
authors.forename: De Yun
authors.initials: de Y
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authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Leonard H
authors.initials: LH
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authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Jan H
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authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Olaf
authors.initials: O
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authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: Seiko
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authors.affiliation: Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Veikko
authors.initials: V
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authors.affiliation: Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Neuherberg, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Strauch
authors.affiliation: Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre Rotterdam, the Netherlands; The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden/ Rotterdam, the Netherlands.
authors.forename: Joyce B J
authors.initials: JB
authors.lastname: van Meurs
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.affiliation: Groningen Bioinformatics Centre, University of Groningen, Groningen, The Netherlands.
authors.forename: Ritsert C
authors.initials: RC
authors.lastname: Jansen
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Lude
authors.initials: L
authors.lastname: Franke
mesh_terms: D002460:Cell Line; D003424:Crohn Disease / Q000235:genetics; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D040641:Quantitative Trait Loci; D015203:Reproducibility of Results
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein