ArticleNature genetics2021
Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression.
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Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,524 papers, 6 of them syntheses that pooled it.
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1,524citing papers in PubMed, 6 pooled it
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Who cites it
1,524 citing papers in PubMed, 6 syntheses or guidelines pooled it.
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- Machine learning and statistical methods for molecular quantitative trait loci.Nature reviews. Genetics · 2026Review
- Genetically predicted ZDHHC8 expression and osteoporosis risk: A two-sample Mendelian randomization and metabolite mediation study.Medicine · 2026Article
1,464 more citing papers are in PubMed but not listed here.
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Authors and funding
110 authors.
Urmo Võsa *Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. urmo.vosa@gmail.com.ORCID http://orcid.org/0000-0003-3476-1652
Annique Claringbould *Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. anniqueclaringbould@gmail.com.ORCID http://orcid.org/0000-0002-9201-6557
Harm-Jan WestraDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0001-7038-567X
Marc Jan BonderDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Patrick DeelenDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-5654-3966
Biao ZengSchool of Biological Sciences, Georgia Tech, Atlanta, GA, USA.
Holger KirstenInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.ORCID http://orcid.org/0000-0002-3126-7950
Ashis SahaDepartment of Computer Science, Johns Hopkins University, Baltimore, MD, USA.
Roman KreuzhuberDepartment of Haematology, University of Cambridge, Cambridge, United Kingdom.
Seyhan YazarGarvan Institute of Medical Research, Garvan-Weizmann Centre for Cellular Genomics, Sydney, New South Wales, Australia.
Harm BruggeDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Roy OelenDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-5026-6531
Dylan H de VriesDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-0953-0257
Monique G P van der WijstDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Silva KaselaEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Natalia PervjakovaEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Isabel AlvesComputational Biology, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-4303-5479
Marie-Julie FavéComputational Biology, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
Mawussé AgbessiComputational Biology, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
Mark W ChristiansenCardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
Rick JansenDepartment of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-3333-6737
Ilkka SeppäläDepartment of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Lin TongDepartment of Public Health Sciences, University of Chicago, Chicago, IL, USA.
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-8309-094X
Katharina SchrammInstitute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Gibran HemaniMRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
Joost VerlouwDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0003-2373-0981
Hanieh YaghootkarGenetics of Complex Traits, University of Exeter Medical School, Royal Devon & Exeter Hospital, Exeter, United Kingdom.
Reyhan Sönmez FlitmanDepartment of Computational Biology, University of Lausanne, Lausanne, Switzerland.
Andrew BrownDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.ORCID http://orcid.org/0000-0002-8087-3033
Viktorija KukushkinaEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Anette KalnapenkisEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Sina RüegerLausanne University Hospital, Lausanne, Switzerland.ORCID http://orcid.org/0000-0003-2848-9242
Eleonora PorcuLausanne University Hospital, Lausanne, Switzerland.ORCID http://orcid.org/0000-0003-2878-7485
Jaanika KronbergEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Johannes KettunenComputational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland.ORCID http://orcid.org/0000-0002-3345-491X
Bernett LeeSingapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore.
Futao ZhangInstitute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Ting QiInstitute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Jose Alquicira HernandezGarvan Institute of Medical Research, Garvan-Weizmann Centre for Cellular Genomics, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-9049-7780
Wibowo ArindrartoLeiden University Medical Center, Leiden, the Netherlands.
Frank BeutnerHeart Center Leipzig, Universität Leipzig, Leipzig, Germany.
BIOS Consortium
i2QTL Consortium
Julia DmitrievaUnit of Animal Genomics, WELBIO, GIGA-R & Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
Mahmoud ElansaryUnit of Animal Genomics, WELBIO, GIGA-R & Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
Benjamin P FairfaxWellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.ORCID http://orcid.org/0000-0001-7413-5002
Michel GeorgesUnit of Animal Genomics, WELBIO, GIGA-R & Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.ORCID http://orcid.org/0000-0003-4124-2375
Bastiaan T HeijmansLeiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0001-5918-0534
Alex W HewittMenzies Institute for Medical Research, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.ORCID http://orcid.org/0000-0002-5123-5999
Mika KähönenDepartment of Clinical Physiology, Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Yungil KimDepartment of Computer Science, Johns Hopkins University, Baltimore, MD, USA.
Julian C KnightWellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.ORCID http://orcid.org/0000-0002-0377-5536
Peter KovacsIFB Adiposity Diseases, Universität Leipzig, Leipzig, Germany.ORCID http://orcid.org/0000-0002-0290-5423
Knut KrohnInterdisciplinary Center for Clinical Research, Faculty of Medicine, Universität Leipzig, Leipzig, Germany.ORCID http://orcid.org/0000-0001-8110-1273
Shuang LiDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-6634-4856
Markus LoefflerInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Urko M MarigortaSchool of Biological Sciences, Georgia Tech, Atlanta, GA, USA.
Hailang MeiDepartment of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
Yukihide MomozawaUnit of Animal Genomics, WELBIO, GIGA-R & Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
Martina Müller-NurasyidInstitute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0003-3793-5910
Matthias NauckDZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-6678-7964
Michel G NivardDepartment of Biological Psychology, Faculty of Behaviour and Movement Sciences, Vrije Universiteit, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-2015-1888
Brenda W J H PenninxDepartment of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam, the Netherlands.
Jonathan K PritchardDepartment of Biology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-8828-5236
Olli T RaitakariResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Olaf RotzschkeSingapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore.
Eline P SlagboomLeiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0002-2875-4723
Coen D A StehouwerDepartment of Internal Medicine and School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, Maastricht, the Netherlands.
Michael StumvollDepartment of Medicine, Universität Leipzig, Leipzig, Germany.
Patrick SullivanDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Peter A C 't HoenCenter for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center Nijmegen, Nijmegen, the Netherlands.ORCID http://orcid.org/0000-0003-4450-3112
Joachim ThieryLIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
Anke TönjesDepartment of Medicine, Universität Leipzig, Leipzig, Germany.
Jenny van DongenNetherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-2063-8741
Maarten van ItersonLeiden University Medical Center, Leiden, the Netherlands.
Jan H VeldinkUMC Utrecht Brain Center, University Medical Center Utrecht, Department of Neurology, Utrecht University, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0001-5572-9657
Uwe VölkerInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-5689-3448
Robert WarmerdamDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0001-8691-0053
Cisca WijmengaDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-5635-1614
Morris SwertzGenomics Coordination Center, University Medical Centre Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-0979-3401
Anand AndiappanSingapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore.ORCID http://orcid.org/0000-0002-8442-1544
Grant W MontgomeryInstitute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-4140-8139
Samuli RipattiInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-0504-1202
Markus PerolaNational Institute for Health and Welfare, University of Helsinki, Helsinki, Finland.
Zoltan KutalikCenter for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
Emmanouil DermitzakisSwiss Institute of Bioinformatics, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-9302-6490
Sven BergmannDepartment of Computational Biology, University of Lausanne, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-6785-9034
Timothy FraylingGenetics of Complex Traits, University of Exeter Medical School, Royal Devon & Exeter Hospital, Exeter, United Kingdom.ORCID http://orcid.org/0000-0001-8362-2603
Joyce van MeursDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
Holger ProkischInstitute of Neurogenomics, Helmholtz Zentrum München, Neuherberg, Germany.ORCID http://orcid.org/0000-0003-2379-6286
Habibul AhsanDepartment of Public Health Sciences, University of Chicago, Chicago, IL, USA.
Brandon L PierceDepartment of Public Health Sciences, University of Chicago, Chicago, IL, USA.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Dorret I BoomsmaNetherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-7099-7972
Bruce M PsatyCardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7278-2190
Sina A GharibCardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-2480-4367
Philip AwadallaComputational Biology, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
Lili MilaniEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.ORCID http://orcid.org/0000-0002-5323-3102
Willem H OuwehandDepartment of Haematology, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0002-7744-1790
Kate DownesDepartment of Haematology, University of Cambridge, Cambridge, United Kingdom.
Oliver StegleGenome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-8818-7193
Alexis BattleDepartment of Computer Science, Johns Hopkins University, Baltimore, MD, USA.
Peter M VisscherInstitute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-2143-8760
Jian YangInstitute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0003-2001-2474
Markus ScholzInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.ORCID http://orcid.org/0000-0002-4059-1779
Joseph PowellGarvan Institute of Medical Research, Garvan-Weizmann Centre for Cellular Genomics, Sydney, New South Wales, Australia.
Greg GibsonSchool of Biological Sciences, Georgia Tech, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-5352-5877
Tõnu EskoEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.ORCID http://orcid.org/0000-0003-1982-6569
Lude FrankeDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. lude@ludesign.nl.ORCID http://orcid.org/0000-0002-5159-8802
Funding
Utilizing Technology and AI Approaches to Facilitate Independence andResilience in Older AdultsP30AG073104 · NIA · JOHNS HOPKINS UNIVERSITY · PI Alexis Battle · 2021 to 2026
$31.2MChemoprevention of arsenic-induced skin cancerR01CA107431 · NCI · UNIVERSITY OF CHICAGO · PI AHSAN, HABIBUL · 2005 to 2014
$17.3MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MArsenic and the Human Genome: susceptibility and response to exposure Supplement 4R35ES028379 · NIEHS · UNIVERSITY OF CHICAGO · PI PIERCE, BRANDON LEE · 2017 to 2024
$5.6MIntegrative multivariate association and genomic analysesR01GM108711 · NIGMS · UNIVERSITY OF CHICAGO · PI CHEN, LIN · 2014 to 2022
$3.1MGenetics of arsenic metabolism: fine-mapping and rare variant analysisR01ES023834 · NIEHS · UNIVERSITY OF CHICAGO · PI PIERCE, BRANDON LEE · 2014 to 2017
$2.5MMethods for high-resolution analysis of genetic effects on gene expressionR01MH101814 · NIMH · UNIVERSITY OF GENEVA · PI BUSTAMANTE, CARLOS DANIEL, DERMITZAKIS, EMMANOUIL · 2013 to 2016
$2.3MA Study of Telomeres in an Arsenic-Exposed Bangladesh CohortR01ES020506 · NIEHS · UNIVERSITY OF CHICAGO · PI PIERCE, BRANDON LEE · 2011 to 2015
$1.9MPredicting causal non-coding variants in a founder populationR01HG008150 · NHGRI · STANFORD UNIVERSITY · PI MONTGOMERY, STEPHEN · 2015 to 2017
$1.4M3/3 Building integrative CNS networks for genomic analysis of autismR01MH109905 · NIMH · JOHNS HOPKINS UNIVERSITY · PI BATTLE, ALEXIS · 2016 to 2020
$1.2MIdentifying arsenic susceptibility variants using a functional screening approachR21ES024834 · NIEHS · UNIVERSITY OF CHICAGO · PI ARGOS, MARIA, PIERCE, BRANDON LEE · 2015 to 2017
$490kMedical Research Council G9815508Medical Research Council MC_PC_15018Medical Research Council MC_PC_19009NCI NIH HHS R01 CA107431NHGRI NIH HHS R01 HG008150NHLBI NIH HHS R01 HL105756NIA NIH HHS P30 AG073104NIEHS NIH HHS R01 ES020506NIEHS NIH HHS R01 ES023834NIEHS NIH HHS R21 ES024834NIEHS NIH HHS R35 ES028379NIGMS NIH HHS R01 GM108711NIMH NIH HHS R01 MH101814NIMH NIH HHS R01 MH109905Wellcome Trust 201488/Z/16/Z
Abstract
Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues. Distal trans-eQTL (detected for 37% of 10,317 trait-associated variants tested) showed lower replication rates, partially due to low replication power and confounding by cell type composition. However, replication analyses in single-cell RNA-seq data prioritized intracellular trans-eQTL. Trans-eQTL exerted their effects via several mechanisms, primarily through regulation by transcription factors. Expression of 13% of the genes correlated with polygenic scores for 1,263 phenotypes, pinpointing potential drivers for those traits. In summary, this work represents a large eQTL resource, and its results serve as a starting point for in-depth interpretation of complex phenotypes.
Indexed as
Blood ProteinsGene Expression RegulationGenome-Wide Association StudyHumansMultifactorial InheritancePolymorphism, Single NucleotideQuantitative Trait LociTranscriptomeBlood Proteins
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