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PLoS Genet. 2015 May 8;11(5):e1005223. doi: 10.1371/journal.pgen.1005223. eCollection 2015 May.

Cell Specific eQTL Analysis without Sorting Cells.

Author information

1
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
2
Groningen Bioinformatics Centre, University of Groningen, Groningen, The Netherlands.
3
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.
4
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.
5
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.
6
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institut für Humangenetik, Technische Universität München, München, Germany.
7
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.
8
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
9
Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom; Department of Oncology, Cancer and Haematology Centre, Churchill Hospital, Oxford, United Kingdom.
10
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
11
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands; Groningen Bioinformatics Centre, University of Groningen, Groningen, The Netherlands.
12
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.
13
University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands.
14
Estonian Genome Center, University of Tartu, Tartu, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
15
Estonian Genome Center, University of Tartu, Tartu, Estonia.
16
Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
17
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.
18
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.
19
Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
20
Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
21
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
22
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.
23
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.
24
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.
25
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
26
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.
27
Estonian Genome Center, University of Tartu, Tartu, Estonia; Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
28
Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, United Kingdom.
29
Clinical Research Branch, National Institute on Aging NIA-ASTRA Unit, Harbor Hospital, Baltimore, Maryland, United States of America.
30
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
31
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.
32
Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
33
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.
34
Department of Otolaryngology, National University of Singapore, Singapore.
35
Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands.
36
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
37
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.

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.

PMID:
25955312
PMCID:
PMC4425538
DOI:
10.1371/journal.pgen.1005223
[Indexed for MEDLINE]
Free PMC Article

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