Evidence map›Paper›PMID 24013639›Full record

ArticleNature genetics2013

Systematic identification of trans eQTLs as putative drivers of known disease associations.

Harm-Jan Westra, Marjolein J Peters, Tõnu Esko, Hanieh Yaghootkar, Claudia Schurmann, Johannes Kettunen, Mark W Christiansen, Benjamin P Fairfax, Katharina Schramm, Joseph E Powell and 49 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,085 papers, 16 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,085citing papers in PubMed, 16 pooled it
105.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1,085 citing papers in PubMed, 16 syntheses or guidelines pooled it, 1,757 citations in OpenAlex.

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  9. Integration ofFrontiers in immunology · 2023
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  20. ZDHHC5 may regulate the function of NKT cells and the immune response in Meniere's disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Article

1,025 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

59 authors at 20 institutions in 8 countries.

Harm-Jan Westra *Department of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, the Netherlands.
Marjolein J Peters *Department of Internal Medicine, Erasmus Medical Centre Rotterdam, the Netherlands.
Tõnu Esko *Estonian Genome Center, University of Tartu, Riia 23b, 51010, Tartu, Estonia.
Hanieh Yaghootkar *Genetics of Complex Traits, University of Exeter Medical School, Exeter, EX1 2LU, UK.
Claudia Schurmann *Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17487 Greifswald, Germany.
Johannes Kettunen *Institute for Molecular Medicine Finland FIMM, FI-00014 University of Helsinki, Helsinki, Finland.
Mark W Christiansen *Cardiovascular Health Research Unit, University of Washington, Seattle, WA.
Benjamin P FairfaxWellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
Katharina SchrammInstitute of Human Genetics, Helmholz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Joseph E PowellUniversity of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Alexandra ZhernakovaDepartment of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, the Netherlands.
Daria V ZhernakovaDepartment of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, the Netherlands.
Jan H VeldinkDepartment of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, the Netherlands.
Leonard H Van den BergDepartment of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, the Netherlands.
Juha KarjalainenDepartment of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, the Netherlands.
Sebo WithoffDepartment of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, the Netherlands.
André G UitterlindenDepartment of Internal Medicine, Erasmus Medical Centre Rotterdam, the Netherlands.
Albert HofmanThe Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden/Rotterdam, the Netherlands.
Fernando RivadeneiraDepartment of Internal Medicine, Erasmus Medical Centre Rotterdam, the Netherlands.
Peter A C 't HoenCenter for Human and Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Eva ReinmaaEstonian Genome Center, University of Tartu, Riia 23b, 51010, Tartu, Estonia.
Krista FischerEstonian Genome Center, University of Tartu, Riia 23b, 51010, Tartu, Estonia.
Mari NelisEstonian Genome Center, University of Tartu, Riia 23b, 51010, Tartu, Estonia.
Lili MilaniEstonian Genome Center, University of Tartu, Riia 23b, 51010, Tartu, Estonia.
David MelzerInstitute of Biomedical and Clinical Sciences, University of Exeter Medical School, Barrack Road, Exeter, EX2 5DW, UK.
Luigi FerrucciClinical Research Branch, National Institute on Aging NIA-ASTRA Unit, Harbor Hospital, MD, USA.
Andrew B SingletonLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Lincoln Drive, Bethesda, MD, USA.
Dena G HernandezLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Lincoln Drive, Bethesda, MD, USA.
Michael A NallsLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Lincoln Drive, Bethesda, MD, USA.
Georg HomuthDepartment of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17487 Greifswald, Germany.
Matthias NauckInstitute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany.
Dörte RadkeInstitute for Community Medicine, University Medicine Greifswald, D-17487 Greifswald, Germany.
Uwe VölkerDepartment of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17487 Greifswald, Germany.
Markus PerolaEstonian Genome Center, University of Tartu, Riia 23b, 51010, Tartu, Estonia.
Veikko SalomaaDepartment of Chronic Disease Prevention, National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
Jennifer BrodyCardiovascular Health Research Unit, University of Washington, Seattle, WA.
Astrid Suchy-DiceyDepartment of Epidemiology, University of Washington, Seattle, WA, USA.
Sina A GharibComputational Medicine Core, Center for Lung Biology, Division of Pulmonary & Critical Care Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.
Daniel A EnquobahrieDepartment of Epidemiology, University of Washington, Seattle, WA, USA.
Thomas LumleyDepartment of Statistics, University of Auckland, Auckland, New Zealand.
Grant W MontgomeryQueensland Institute of Medical Research, Herston, Brisbane, Australia.
Seiko MakinoWellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
Holger ProkischInstitute of Human Genetics, Helmholz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Christian HerderInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, University Düsseldorf, Düsseldorf, Germany.
Michael RodenInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, University Düsseldorf, Düsseldorf, Germany.
Harald GrallertResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Thomas MeitingerInstitute of Human Genetics, Helmholz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Konstantin StrauchInstitute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Neuherberg, Germany.
Yang LiGroningen Bioinformatics Centre, University of Groningen, Groningen, the Netherlands.
Ritsert C JansenGroningen Bioinformatics Centre, University of Groningen, Groningen, the Netherlands.
Peter M VisscherUniversity of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Julian C KnightWellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
Bruce M Psaty *Cardiovascular Health Research Unit, University of Washington, Seattle, WA.
Samuli Ripatti *Institute for Molecular Medicine Finland FIMM, FI-00014 University of Helsinki, Helsinki, Finland.
Alexander Teumer *Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17487 Greifswald, Germany.
Timothy M Frayling *Genetics of Complex Traits, University of Exeter Medical School, Exeter, EX1 2LU, UK.
Andres Metspalu *Estonian Genome Center, University of Tartu, Riia 23b, 51010, Tartu, Estonia.
Joyce B J van Meurs *Department of Internal Medicine, Erasmus Medical Centre Rotterdam, the Netherlands.
Lude Franke *Department of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, the Netherlands.
Universitätsmedizin Greifswald · DEUniversity Medical Center Groningen · NLUniversity of Tartu · EEHelmholtz Zentrum München · DEUniversity of Washington · USCentre for Human Genetics · GBErasmus MC · NLNational Institutes of Health · USUniversity of Exeter · GBFinnish Institute for Health and Welfare · FINetherlands Consortium for Healthy Ageing · NLThe University of Queensland · AUUniversity Medical Center Utrecht · NLUniversity of Groningen · NLDeutsches Diabetes-Zentrum e.V. · DEDüsseldorf University Hospital · DEGroup Health Cooperative · USLeiden University Medical Center · NLNational Institute on Aging · USQIMR Berghofer Medical Research Institute · AU

Funding

Genome-wide case-only study of antihypertensive drug-gene interactionsR01HL085251 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2007 to 2010
$7.2M
Estrogens and pharmacogenetic risks of venous thrombosis in postmenopausal womenR01HL073410 · NHLBI · UNIVERSITY OF WASHINGTON · PI SMITH, NICHOLAS L · 2004 to 2012
$4.8M
Intramural NIH HHS Z99 AG999999Medical Research Council G0500070NHLBI NIH HHS R01 HL073410NHLBI NIH HHS R01 HL085251Wellcome Trust 090532
6 · The paper itself

Abstract

Identifying the downstream effects of disease-associated SNPs is challenging. To help overcome this problem, we performed expression quantitative trait locus (eQTL) meta-analysis in non-transformed peripheral blood samples from 5,311 individuals with replication in 2,775 individuals. We identified and replicated trans eQTLs for 233 SNPs (reflecting 103 independent loci) that were previously associated with complex traits at genome-wide significance. Some of these SNPs affect multiple genes in trans that are known to be altered in individuals with disease: rs4917014, previously associated with systemic lupus erythematosus (SLE), altered gene expression of C1QB and five type I interferon response genes, both hallmarks of SLE. DeepSAGE RNA sequencing showed that rs4917014 strongly alters the 3' UTR levels of IKZF1 in cis, and chromatin immunoprecipitation and sequencing analysis of the trans-regulated genes implicated IKZF1 as the causal gene. Variants associated with cholesterol metabolism and type 1 diabetes showed similar phenomena, indicating that large-scale eQTL mapping provides insight into the downstream effects of many trait-associated variants.

Indexed as

Genetic Predisposition to DiseaseQuantitative Trait LociDiabetes Mellitus, Type 1HumansLupus Erythematosus, SystemicPolymorphism, Single Nucleotide

Identifiers

PMID24013639
PMCPMC3991562
OpenAlexW2135199713

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.