Evidence map›Paper›PMID 42097137›Full record

ArticleCell2026

Multi-cohort proteogenomic analyses reveal genetic effects across the proteome and diseasome.

Mine Koprulu, Karl Smith-Byrne, Brian Richard Ferolito, Erin Macdonald-Dunlop, Jian'an Luan, Åsa K Hedman, Chibuzor Franklin Ogamba, Jurgis Kuliesius, Linda Repetto, Anna Ramisch and 108 more

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Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Proteogenomics in human populations.Nature reviews. Genetics · 2026
    Review
  3. Article
  4. Review
4 · The record

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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

118 authors.

Mine KopruluPrecision Healthcare University Research Institute, Queen Mary University of London, London E1 1HH, UK; MRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Computational Medicine, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin 10117, Germany. Electronic address: m.koprulu@qmul.ac.uk.
Karl Smith-ByrneCancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
Brian Richard FerolitoMillion Veteran Program (MVP) Coordinating Center, Veterans Affairs Healthcare System, Boston, MA 02111, USA.
Erin Macdonald-DunlopDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 65, Sweden; Pfizer Research and Development, Pfizer, Stockholm 113 63, Sweden; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh EH16 4UX, UK.
Jian'an LuanMRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
Åsa K HedmanPfizer Research and Development, Pfizer, Stockholm 113 63, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden.
Chibuzor Franklin OgambaCancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
Jurgis KuliesiusCentre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh EH16 4UX, UK.
Linda RepettoCentre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh EH16 4UX, UK; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu 51010, Estonia.
Anna RamischDepartment of Genetic Medicine and Development, Faculty of Medicine, University of Geneva Medical School, Geneva 1211, Switzerland.
Fahim AbbasiDivision of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 90305-5406, USA.
Johan ÄrnlövSchool of Health and Social Studies, Dalarna University, Falun 79188, Sweden; Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm 14183, Sweden.
Themistocles L AssimesDepartment of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
BeLOVE Study GroupBerlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin 10178, Germany; Institute of Medical Informatics, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin 10115, Germany; Center for Stroke Research (CSB), Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität Berlin, Berlin 10117, Germany; Department of Neurology with experimental Neurology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität Berlin, Berlin 10117, Germany; Institute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität Berlin, Berlin 10117, Germany; Department of Endocrinology and Metabolism, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität Berlin, Berlin 10117, Germany; Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität Berlin, Berlin 13353, Germany; Department of Cardiology, Angiology and Intensive Care Medicine, Campus Virchow Klinikum, Deutsches Herzzentrum der Charité (DHZC), Berlin 13353, Germany; DZHK Partner Site Berlin, DZHK (German Centre for Cardiovascular Research), Berlin 10785, Germany; Biobank Technology Platform, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 13125, Germany; Genetics and Genomics of Cardiovascular Diseases, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 13125, Germany; Hypertension-Caused End-Organ Damage, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 13125, Germany; Integrative Vascular Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 13125, Germany.
Hanna M BjörckDivision of Cardiology, Center for Molecular Medicine, Karolinska University Hospital, Solna, Stockholm, Sweden.
Sophia BjörkanderDivision of Cardiology, Center for Molecular Medicine, Karolinska University Hospital, Solna, Stockholm, Sweden.
Morten BöttcherDepartment of Clinical Medicine, Aarhus University, Aarhus 8000, Denmark; Department of Cardiology, Gødstrup Hospital, Herning 7400, Denmark.
Adam Stuart ButterworthBritish Heart Foundation Centre of Research Excellence, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0BB, UK; Department of Public Health and Primary Care, British Heart Foundation Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge CB2 0BB, UK; NIHR Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge CB2 0BB, UK; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge CB2 0BB, UK; Health Data Research UK, Wellcome Genome Campus, University of Cambridge, Hinxton CB10 1RQ, UK.
Zhengming ChenNuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
Kelly ChoMillion Veteran Program (MVP) Coordinating Center, Veterans Affairs Healthcare System, Boston, MA 02111, USA; Division of Aging, Mass General Brigham, Harvard Medical School, Boston, MA 02130, USA.
Robert Joseph ClarkeNuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
Simon Riddington CoxLothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Kamila CzeneDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden.
John DaneshDepartment of Public Health and Primary Care, British Heart Foundation Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge CB2 0BB, UK; British Heart Foundation Centre of Research Excellence, School of Clinical Medicine, Addenbrooke's Hospital, School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 0BB, UK; Public Health and Primary Care, Victor Phillip Dahdaleh Heart and Lung Research Institute, Cambridge CB2 0BB, UK; Health Data Research UK Cambridge, Wellcome Genome Campus, University of Cambridge, Cambridge CB2 0BB, UK; Department of Human Genetics, Wellcome Sanger Institute, Cambridge CB10 1SA, UK.
George DedoussisNutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens 17671, Greece.
Sölve ElmståhlDepartement of Clinical Sciences in Malmö, Lund University, Malmö 205 02, Sweden.
Niclas ErikssonUppsala Clinical Research Center, Uppsala University, Uppsala 751 85, Sweden.
Per ErikssonDepartment of Medicine Solna, Karolinska Institutet, Stockholm 17177, Sweden.
Tõnu EskoEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu 51010, Estonia.
Estonian Biobank Research TeamEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu 51010, Estonia.
Aida Ferreiro-IglesiasGenomic Epidemiology Branch (GEM), International Agency for Research on Cancer (IARC), Lyon 69007, France.
Paul William FranksPrecision Healthcare University Research Institute, Queen Mary University of London, London E1 1HH, UK; Department of Clinical Sciences, Lund University, Helsingborg 25187, Sweden.
Jingyuan FuDepartment of Genetics, University Medical Center Groningen, Groningen 9713GZ, the Netherlands; Department of Pediatrics, University Medical Center Groningen, Groningen 9713GZ, the Netherlands.
J Michael GazianoDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02120, USA; Department of Medicine, VA Boston Healthcare System, Boston, MA 02132, USA.
Mohsen GhanbariDepartment of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam 3015 GD, the Netherlands.
Christian GiegerGerman Center for Diabetes Research (DZD), Neuherberg 85764, Germany; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany.
Arthur GillyInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany.
Harald GrallertInstitute of Epidemiology, Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany.
Marc James GunterSchool of Public Health, Imperial College London, London W12 0BZ, UK.
Stefan GustafssonDepartment of Medical Sciences, Uppsala University, Uppsala 75185, Sweden.
Andreas GötesonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology at the Sahlgrenska Academy, University of Gothenburg, Gothenburg 41346, Sweden.
Per Frans Leonard HallDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden; Department of Oncology, Södersjukhuset, Stockholm 118 83, Sweden.
Oskar HanssonClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund 22100, Sweden.
Sarah Elizabeth HarrisLothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Caroline HaywardInstitute for Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK.
Christian HerderPartner Düsseldorf, German Center for Diabetes Research (DZD), Neuherberg 85764, Germany; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf 40225, Germany; Division of Endocrinology and Diabetology, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf 40225, Germany.
Natalia Hernandez-PachecoDivision of Cardiology, Center for Molecular Medicine, Karolinska University Hospital, Solna, Stockholm, Sweden.
Ziad HijaziDepartment of Medical Sciences, Cardiology, Uppsala University, Uppsala 75185, Sweden.
Robert F HillaryDepartment of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Jemma Caroline HopewellNuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
Shixian HuInstitute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
Shih-Jen HwangDepartment of Biostatistics, Boston University, Boston, MA 02215, USA; Population Sciences Branch, National Heart Lung and Blood Institute, National Institute of Health, Framingham, MA 01702, USA.
Christina JernDepartment of Laboratory Medicine, Institute of Biomedicine, Gothenburg 405 30, Sweden; Clinical Genetics and Genomics, Sahlgrenska University Hospita, Gothenburg 413 45, Sweden.
Åsa JohanssonImmunology, Genetics and Pathology, Uppsala University, Uppsala 74895, Sweden.
Lina JonssonInstitute of Neuroscience and Physiology, University of Gothenburg, Gothenburg 41345, Sweden.
Anette KalnapenkisEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu 51010, Estonia.
Nicola Dorothy KerrisonMRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
Pik Fang KhoAlnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA; Cardiovascular Medicine, Stanford University, Stanford, CA 94305, USA.
Lucija KlaricMRC Human Genetics Unit, University of Edinburgh, Edinburgh EH4 2XU, UK.
Leonhard KohleickComputational Medicine, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin 10117, Germany.
Julia KraftStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin 10117, Germany; German Center for Mental Health (DZPG), Partner Site Berlin/Potsdam, Berlin 10117, Germany.
Mikael LandénDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden; Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg 413 45, Sweden.
Daniel LevyPopulation Sciences Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Framingham, MA 02461, USA; Framingham Heart Study, Framingham, MA 01702, USA.
Liming LiSchool of Public Health, Peking University, Beijing 100191, China.
Lars LindDepartment of Medical Sciences, Uppsala University, Uppsala 75185, Sweden.
Jirong LongDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37213, USA.
Niklas Mattsson-CarlgrenClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö 20213, Sweden.
Erik MelénDepartment of Clinical Science and Education, Karolinska Institutet, Stockholm 118 83, Sweden.
Simon Kebede MeridDepartment of Clinical Science and Education, Karolinska Institutet, Stockholm 118 83, Sweden.
Philipp MertinsCore Unit Proteomics, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin 13125, Germany; Proteomics Platform, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
Karl MichaëlssonMedical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala 751 85, Sweden.
Peter Loof MøllerDepartment of Health Science and Technology, Aalborg University, Gistrup 9260, Denmark.
Federico MurgiaClinical Trial Service Unit, Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
Mette NyegaardDepartment of Health Science and Technology, Aalborg University, Gistrup 9260, Denmark; Department of Congenital Disorders, Statens Serum Institute, Copenhagen 2300, Denmark.
Young-Chan ParkInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany.
Ewan PearsonDepartment of Diabetes, Endocrinology & Reproductive Biology, University of Dundee, Dundee DD1 9SY, UK.
James PetersDepartment of Immunology and Inflammation, Imperial College London, London W120HS, UK.
John Ross PetrieRobertson Centre for Biostatistics, School of Health and Wellbeing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G128TB, UK.
Grace PngInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany.
Ozren PolašekDepartment of Public Health, University of Split, School of Medicine, Split 21000, Croatia.
Bram Peter PrinsBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0BB, UK.
Stephan RipkeStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin 10117, Germany; German Center for Mental Health, DZPG, site Berlin-Potsdam, Berlin 10117, Germany.
Michael RodenPartner Düsseldorf, German Center for Diabetes Research (DZD), Neuherberg 80992, Germany; Institute of Clinical Diabetology, German Diabetes Center, Düsseldorf 40225, Germany; Department of Endocrinology and Diabetology, Heinrich Heine University, Düsseldorf 40225, Germany.
Palle Duun RohdeDepartment of Health Science and Technology, Aalborg University, Gistrup 9260, Denmark.
Saredo SaidPartner Düsseldorf, German Center for Diabetes Research (DZD), Neuherberg 80992, Germany; Novo Nordisk Research Centre Oxford, Novo Nordisk, Oxford OX3 7FZ, UK.
SCALLOP ConsortiumSCALLOP Consortium.
Xia ShenCentre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh EH16 4UX, UK; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden; Greater Bay Area Institute of Precision Medicine, State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, School of Life Sciences, Fudan University, Shanghai 200032, China.
Jochen M SchwenkScience for Life Laboratory, Department of Protein Science, KTH Royal Institute of Technology, Solna 171 65, Sweden.
Agneta SiegbahnDepartment of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala 75185, Sweden.
J Gustav SmithDepartment of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University, Gothenburg 413 34, Sweden; Science for Life Laboratory, Gothenburg University, Gothenburg 413 34, Sweden; Department of Cardiology, Clinical Sciences, Lund University, Lund 221 84, Sweden; Wallenberg Center for Molecular Medicine, Lund University Diabetes Center, Lund University, Lund 221 84, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg 413 34, Sweden; Department of Heart Failure and Valvular Disease, Skåne University Hospital, Lund 221 85, Sweden.
Tara M StanneDepartment of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg 413 90, Sweden; Institute of Biomedicine, Department of Laboratory Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg 405 30, Sweden.
Karsten SuhreEnglander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10021, USA; Bioinformatics Core, Weill Cornell Medicine-Qatar, Doha 24144, Qatar.
Johan SundströmDepartment of Medical Sciences, Uppsala University, Uppsala 75185, Sweden; The George Institute for Global Health, University of New South Wales, Sydney, NSW 2031, Australia.
Barbara ThorandInstitute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany; Partner Munich-Neuherberg, German Center for Diabetes Research (DZD), Neuherberg 85764, Germany; Institute for Medical Information Processing, Biometry and Epidemiology - IBE, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich, Munich 81377, Germany.
Elsa Valdes-MarquezNuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
Costanza L VallergaGenomics Core Facility, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3015 GD, the Netherlands.
Joyce B J van MeursGenomics Core Facility, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3015 GD, the Netherlands; Department of Orthopedics and Sports Medicine, Erasmus Medical Center, Rotterdam 3000DR, the Netherlands.
Ana ViñuelaPopulation Health and Genomics, University of Dundee, Dundee DD19SY, UK.
Urmo VõsaEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu 51010, Estonia.
Lars WallentinDepartment Medical Sciences, Uppsala University, Uppsala 75285, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala 75185, Sweden.
Robin G WaltersNuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
Nicholas John WarehamMRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
Joachim Eduard WeberDZHK Partner Site Berlin, DZHK (German Centre for Cardiovascular Research), Berlin 10785, Germany; BeLOVE Unit, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin 10178, Germany; Center for Stroke Research (CSB), Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität Berlin, Berlin 12203, Germany; Department of Neurology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität Berlin, Berlin 12203, Germany.
Rinse Karel WeersmaDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen 9700RB, the Netherlands.
James F WilsonCentre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh EH16 4UX, UK; Institute for Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK.
Simon WintherDepartment of Cardiology, Gødstrup Hospital, Herning 7400, Denmark.
Summaira YasmeenComputational Medicine, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin 10117, Germany.
Daniela ZanettiNational Research Council, Institute of Genetic and Biomedical Research, Cagliari 09042, Italy; Department of Medicine, Stanford University School of Medicine, Palo Alto, CA 94305, USA.
Eleftheria ZegginiInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany; TUM School of Medicine and Health, Technical University of Munich (TUM), TUM University Hospital, Munich 81675, Germany.
Jing Hua ZhaoDepartment of Public Health and Primary Care, British Heart Foundation Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge CB1 8RN, UK; Victor Phillip Dahdaleh Heart & Lung Research Institute, University of Cambridge, Cambridge CB2 0BB, UK.
Alexandra ZhernakovaDepartment of Genetics, University of Groningen, Medical Center Groningen, Groningen 9700 RB, the Netherlands.
Daria V ZhernakovaDepartment of Genetics, University of Groningen, Medical Center Groningen, Groningen 9700 RB, the Netherlands.
Matthias ZiehmCore Unit Proteomics, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin 13125, Germany; Proteomics Platform, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 13125, Germany.
Benedikt Mathias KesslerChinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
Alexandre C PereiraDepartment of Aging, Brigham and Women's Hospital, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
Anders MälarstigDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17176, Sweden.
Maik PietznerPrecision Healthcare University Research Institute, Queen Mary University of London, London E1 1HH, UK; MRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Computational Medicine, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin 10117, Germany. Electronic address: maik.pietzner@bih-charite.de.
Claudia LangenbergPrecision Healthcare University Research Institute, Queen Mary University of London, London E1 1HH, UK; MRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Computational Medicine, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin 10117, Germany; Max Planck Institute for Molecular Genetics, Berlin 14195, Germany. Electronic address: claudia.langenberg@qmul.ac.uk.

Funding

Identification of proteins for breast cancer risk: an integrative epidemiologic and genomic studyR01CA293996 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jirong Long, Xiao-Ou Shu · 2024 to 2026
$3.6M
Longitudinal multi-omic biomarkers for neurocognitive decline prior to dementia onsetU01AG083829 · NIA · UNIVERSITY OF EDINBURGH · PI Sarah Elizabeth Harris · 2024 to 2026
$3.5M
Proteomic determinants of direct measures of insulin sensitivityR01DK114183 · NIDDK · STANFORD UNIVERSITY · PI ASSIMES, THEMISTOCLES LEONARD · 2018 to 2022
$3.5M
Identification of Genes and DNA Methylation Markers for Lung Cancer Risk by Integrating Multi-omics DataR01CA249863 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CAI, QIUYIN, LONG, JIRONG · 2021 to 2025
$3.4M
DNA Methylation Markers, Genes and Breast Cancer RiskR01CA247987 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI LONG, JIRONG, YE, FEI · 2021 to 2025
$3.4M
Individual and social contextual factors in relation to DNA methylation, biological aging, and lung cancer riskR01MD015396 · NIMHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CAI, QIUYIN, LONG, JIRONG · 2021 to 2025
$3.3M
NCI NIH HHS R01 CA247987NCI NIH HHS R01 CA249863NCI NIH HHS R01 CA293996NIA NIH HHS U01 AG083829NIDDK NIH HHS R01 DK114183NIMHD NIH HHS R01 MD015396
6 · The paper itself

Abstract

Understanding the genetic regulation of circulating protein levels can provide new insights into disease mechanisms. Here, we present the largest proteogenomic study to date (n = 78,664 participants across 38 studies), identifying >24,000 protein quantitative trait loci (QTLs) associated with 1,116 proteins, acting near to (n = 5,040) or distant (n = 19,698) from the cognate gene. Using machine learning-guided effector gene assignment, we provide genetic evidence for pathways, cell types, and tissues that modulate circulating protein levels, highlighting N-linked glycosylation as an important regulatory pathway. We demonstrate that genetic instruments of protein production/function ("cis") versus modulation ("trans") reveal distinct phenotypic insights. We identify proteins as candidates for drug targets and engagement (e.g., plasma furin and cardiovascular diseases) by comparing cis-based genetic evidence with protein-disease associations. Systematic triangulation of trans-protein QTLs (pQTLs) with genetic and protein associations across many diseases highlights potential drug repurposing opportunities, e.g., tyrosine kinase 2 (TYK2) inhibitors for rheumatoid arthritis. Our multi-cohort meta-analyses generate proteogenomic insights into disease mechanisms and new treatment opportunities.

Indexed as

ProteogenomicsProteomeGlycosylationHumansQuantitative Trait LociProteomecausal inferencediseasomedrug repurposingmeta-analysisN-linked glycosylationpleiotropyproteogenomicsproteomicstrans-pQTLs

Identifiers

PMID42097137
PMCPMC13343581

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