ArticleNature communications2023
Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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18citing papers in PubMed, 2 pooled it
19.1field-weighted citation impact, top 1% of its field
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- Use of Mendelian Randomization to Unveil Metabolic Markers inJournal of Korean medical science · 2026Pooled it
- Genome-Wide Meta-analysis Identifies Genetic Variants Associated With Glycemic Response to Sulfonylureas.Diabetes care · 2021Pooled it
- Proteogenomics in human populations.Nature reviews. Genetics · 2026Review
- Focus on single-gene effects limits discovery and interpretation of complex-trait-associated variants.American journal of human genetics · 2026Article
- Federated causal discovery in medicine: trends, opportunities, and challenges.Frontiers in digital health · 2026Article
- Application of Mendelian randomization to explore metabolic pathways in colorectal cancer.Annals of medicine and surgery (2012) · 2025Article
- Integrative Genomics Refines Tissues, Candidate Genes and Putative Regulatory Links Involved in the Humic Adaptation of Keystone Freshwater Fish.Molecular ecology · 2025Article
- Bayesian network imputation methods applied to multi-omics data identify putative causal relationships in a type 2 diabetes dataset containing incomplete data: An IMI DIRECT Study.PLoS genetics · 2025Article
- A map of blood regulatory variation in South Africans enables GWAS interpretation.Nature genetics · 2025Article
- Causal network inference of cis- and trans-gene regulation of expression quantitative trait loci across human tissues.Genetics · 2025Article
- Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle.Communications biology · 2025Article
- Role of human plasma metabolites in prediabetes and type 2 diabetes from the IMI-DIRECT study.Diabetologia · 2024Article
- Statistically and functionally fine-mapped blood eQTLs and pQTLs from 1,405 humans reveal distinct regulation patterns and disease relevance.Nature genetics · 2024Article
- Article
- Cis-eQTLs in seven duck tissues identify novel candidate genes for growth and carcass traits.BMC genomics · 2024Article
- The broad impact of cell death genes on the human disease phenome.Cell death & disease · 2024Article
- The functional impact of rare variation across the regulatory cascade.Cell genomics · 2023Article
- A Bayesian model selection approach to mediation analysis.PLoS genetics · 2022Article
Corrections and comments
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Authors and funding
61 authors at 20 institutions in 13 countries.
Andrew A BrownPopulation Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, United Kingdom.ORCID http://orcid.org/0000-0002-8087-3033
Juan J Fernandez-TajesWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
Mun-Gwan HongScience for Life Laboratory, School of Biotechnology, KTH - Royal Institute of Technology, Solna, SE-171 21, Sweden.ORCID http://orcid.org/0000-0001-8603-8293
Caroline A BrorssonDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
Robert W KoivulaOxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, OX3 7LJ, United Kingdom.
David DavtianPopulation Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, United Kingdom.
Théo DupuisPopulation Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, United Kingdom.
Ambra SartoriDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, 1211, Switzerland.
Theodora-Dafni MichalettouBiosciences Institute, Faculty of Medical Sciences, University of Newcastle, Newcastle upon Tyne, NE1 4EP, United Kingdom.ORCID http://orcid.org/0000-0003-2119-1099
Ian M ForgiePopulation Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, United Kingdom.
Jonathan AdamGerman Center for Diabetes Research (DZD), Neuherberg, 85764, Germany.
Kristine H AllinThe Novo Nordisk Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, DK-2100, Denmark.
Robert CaiazzoUniversity of Lille, Inserm, Lille Pasteur Institute, Lille, France.ORCID http://orcid.org/0000-0001-5383-0540
Henna CederbergInternal Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Federico De MasiDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
Petra J M EldersDepartment of General Practice, Amsterdam UMC- location Vumc, Amsterdam Public Health research institute, Amsterdam, The Netherlands.
Giuseppe N GiordanoDepartment of Clinical Science, Genetic and Molecular Epidemiology, Lund University Diabetes Centre, Malmö, Sweden.ORCID http://orcid.org/0000-0002-6719-6680
Mark HaidMetabolomics and Proteomics Core, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, 85764, Germany.ORCID http://orcid.org/0000-0001-6118-1333
Torben HansenThe Novo Nordisk Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, DK-2100, Denmark.ORCID http://orcid.org/0000-0001-8748-3831
Tue H HansenThe Novo Nordisk Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, DK-2100, Denmark.ORCID http://orcid.org/0000-0001-5948-8993
Andrew T HattersleyDepartment of Clinical and Biomedical Sciences, University of Exeter College of Medicine & Health, Exeter, EX25DW, United Kingdom.ORCID http://orcid.org/0000-0001-5620-473X
Alison J HeggieInstitute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
Cédric HowaldDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, 1211, Switzerland.
Angus G JonesDepartment of Clinical and Biomedical Sciences, University of Exeter College of Medicine & Health, Exeter, EX25DW, United Kingdom.ORCID http://orcid.org/0000-0002-0883-7599
Tarja KokkolaInternal Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.ORCID http://orcid.org/0000-0002-3303-3912
Markku LaaksoInternal Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.ORCID http://orcid.org/0000-0002-3394-7749
Anubha MahajanWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
Andrea MariInstitute of Neuroscience, National Research Council, Padova, 35127, Italy.ORCID http://orcid.org/0000-0002-1436-5591
Timothy J McDonaldBlood Sciences, Royal Devon and Exeter NHS Foundation Trust, Exeter, EX2 5DW, United Kingdom.
Donna McEvoyDiabetes Research Network, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
Miranda MourbyNuffield Department of Population Health, Centre for Health, Law and Emerging Technologies (HeLEX), University of Oxford, Oxford, OX2 7DD, United Kingdom.
Petra B MusholtGlobal Development, Sanofi-Aventis Deutschland GmbH, Hoechst Industrial Park, Frankfurt am Main, 65926, Germany.
Birgitte NilssonDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
Francois PattouUniversity of Lille, Inserm, Lille Pasteur Institute, Lille, France.ORCID http://orcid.org/0000-0001-8388-3766
Deborah PenetDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, 1211, Switzerland.
Violeta RaverdyUniversity of Lille, Inserm, Lille Pasteur Institute, Lille, France.
Martin RidderstråleDepartment of Clinical Science, Lund University, Malmö, Sweden.
Luciana RomanoDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, 1211, Switzerland.
Femke RuttersEpidemiology and Data Science, VUMC, Amsterdam, The Netherlands.
Sapna SharmaResearch Unit of Molecular Epidemiology, Institute of Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, 85764, Germany.
Harriet TeareCentre for Health Law and Emerging Technologies, Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7DQ, United Kingdom.
Leen 't HartEpidemiology and Data Science, VUMC, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-4401-2938
Konstantinos D TsirigosDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
Jagadish VangipurapuInternal Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Henrik VestergaardThe Novo Nordisk Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, DK-2100, Denmark.ORCID http://orcid.org/0000-0003-3090-269X
Søren BrunakDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
Paul W FranksDepartment of Clinical Science, Genetic and Molecular Epidemiology, Lund University Diabetes Centre, Malmö, Sweden.ORCID http://orcid.org/0000-0002-0520-7604
Gary FrostNutrition and Dietetics Research Group, Imperial College London, London, SW7 2AZ, United Kingdom.ORCID http://orcid.org/0000-0003-0529-6325
Harald GrallertGerman Center for Diabetes Research (DZD), Neuherberg, 85764, Germany.
Bernd JablonkaSanofi Partnering, Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, 65926, Germany.
Mark I McCarthyWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
Imre PavoEli Lilly Regional Operations Ges.m.b.H, Vienna, 1030, Austria.ORCID http://orcid.org/0000-0002-2016-7049
Oluf PedersenCenter for Clinical Metabolic Research, Herlev and Gentofte University Hospital, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-3321-3972
Hartmut RuettenSanofi Partnering, Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, 65926, Germany.
Mark WalkerTranslational and Clinical Research Institute, Faculty of Medical Sciences, University of Newcastle, Newcastle upon Tyne, United Kingdom.
DIRECT Consortium
Jerzy AdamskiDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.ORCID http://orcid.org/0000-0001-9259-0199
Jochen M SchwenkScience for Life Laboratory, School of Biotechnology, KTH - Royal Institute of Technology, Solna, SE-171 21, Sweden.ORCID http://orcid.org/0000-0001-8141-8449
Ewan R PearsonPopulation Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, United Kingdom.ORCID http://orcid.org/0000-0001-9237-8585
Emmanouil T Dermitzakis *Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, 1211, Switzerland. emmanouil.dermitzakis@unige.ch.ORCID http://orcid.org/0000-0002-9302-6490
Ana Viñuela *Biosciences Institute, Faculty of Medical Sciences, University of Newcastle, Newcastle upon Tyne, NE1 4EP, United Kingdom. ana.vinuela@newcastle.ac.uk.ORCID http://orcid.org/0000-0003-3771-8537
University of Copenhagen · DKTechnical University of Denmark · DKUniversity of Dundee · GBUniversity of Oxford · GBLund University · SEHelmholtz Zentrum München · DEInserm · FRRoyal Devon & Exeter NHS Foundation Trust · GBUniversity of Geneva · CHBoehringer Ingelheim (Germany) · DENewcastle University · GBSanofi (Germany) · DEUniversity of Eastern Finland · FIAmsterdam UMC Location Vrije Universiteit Amsterdam · NLLeiden University Medical Center · NLSaarland University · DEScience for Life Laboratory · SECentre for Human Genetics · GBEli Lilly (United States) · USNational Research Council · IT
Funding
Medical Research Council MR/R010676/1
Abstract
We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue.
Indexed as
GenomicsMultifactorial InheritanceHumansPhenotypeResearch PersonnelRNA, MessengerRNA, Messenger
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