Evidence map›Paper›PMID 33517400›Full record

ArticleHuman molecular genetics2021

Genome-wide association study of circulating interleukin 6 levels identifies novel loci.

Tarunveer S Ahluwalia, Bram P Prins, Mohammadreza Abdollahi, Nicola J Armstrong, Stella Aslibekyan, Lisa Bain, Barbara Jefferis, Jens Baumert, Marian Beekman, Yoav Ben-Shlomo and 117 more

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In one paragraph

Article in Human molecular genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
–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

34 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  15. Chronic Overlapping Pain Conditions and Nociplastic Pain.medRxiv : the preprint server for health sciences · 2024
    Article
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  20. IL-6 and diabetic kidney disease.Frontiers in immunology · 2024
    Review
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

127 authors.

Tarunveer S AhluwaliaSteno Diabetes Center Copenhagen, Gentofte DK2820, Denmark.ORCID 0000-0002-7464-3354
Bram P PrinsDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.
Mohammadreza AbdollahiDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.
Nicola J ArmstrongMathematics and Statistics, Murdoch University, Perth 6150, Australia.
Stella AslibekyanDepartment of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, Alabama 35233, USA.
Lisa BainQIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
Barbara JefferisDepartment of Primary Care & Population Health, UCL Institute of Epidemiology & Health Care, University College London, London NW3 2PF, UK.
Jens BaumertInstitute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.
Marian BeekmanDepartment of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
Yoav Ben-ShlomoPopulation Health Sciences, University of Bristol, Bristol BS8 2PS, UK.
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
Braxton D MitchellDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD 21202, USA.
Eco de GeusDepartment of Biological Psychology, Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 BT, The Netherlands.
Graciela E DelgadoVth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim 68167, Germany.
Diana MarekSIB Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
Joel ErikssonDepartment of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, Centre for Bone and Arthritis Research (CBAR), University of Gothenburg, Gothenburg 41345, Sweden.
Eero KajantieChronic Disease Prevention Unit, National Institute for Health and Welfare, PO Box 30, Helsinki 00271, Finland.
Stavroula KanoniWilliam Harvey Research Institute, Barts & the London Medical School, Queen Mary University of London, London EC1M 6BQ, UK.
John P KempThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland 4102, Australia.
Chen LuDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
Riccardo E MarioniCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Stela McLachlanUsher Institute, University of Edinburgh, Edinburgh EH8 9AG, UK.
Yuri MilaneschiDepartment of Psychiatry, Amsterdam UMC, Vrije Universiteit, Amsterdam 1081 HJ, The Netherlands.
Ilja M NolteDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.
Alexandros M PetrelisUniversité de Lorraine, Inserm, IGE-PCV, Nancy 54000, France.
Eleonora PorcuIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato (CA) 09042, Italy.
Maria Sabater-LlealCardiovascular Medicine, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
Elnaz NaderiDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.
Ilkka SeppäläDepartment of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland.
Tina ShahInstitute of Cardiovascular Science, University College London, London WC1E 6BT, UK.
Gaurav SinghalDiscipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide 5005, Australia.
Marie StandlInstitute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald 17475, Germany.ORCID 0000-0002-8309-094X
Anbupalam ThalamuthuCentre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia.
Elisabeth ThieringInstitute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.
Stella TrompetDepartment of Cardiology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
Christie M BallantyneBaylor College of Medicine, Houston, TX 77030, USA.
Emelia J BenjaminNational Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA.
Juan P CasasMassachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA.
Catherine TobenDiscipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide 5005, Australia.
George Dedoussis44Department of Nutrition-Dietetics, Harokopio University, Athens 17671, Greece.
Joris DeelenDepartment of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
Peter DurdaDepartment of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA.
Jorgen EngmannInstitute of Cardiovascular Science, University College London, London WC1E 6BT, UK.
Mary F FeitosaDivision of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
Harald GrallertInstitute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.
Ann HammarstedtThe Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg SE-41345, Sweden.
Sarah E HarrisCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Georg HomuthInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17475, Germany.
Jouke-Jan HottengaDepartment of Biological Psychology, Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 BT, The Netherlands.
Sirpa JalkanenMediCity Research Laboratory, University of Turku, Turku 20520, Finland.
Yalda JamshidiGenetics Research Centre, Molecular and Clinical Sciences Institute, St George's University of London, London SW17 0RE, UK.
Magdalene C JawaharDiscipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide 5005, Australia.
Tine Jess55Department of Epidemiology Research, Statens Serum Institute, Copenhagen DK2300, Denmark.
Mika KivimakiDepartment of Epidemiology & Public Health, UCL Institute of Epidemiology & Health Care, University College London, London WC1E 7HB, UK.
Marcus E KleberVth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim 68167, Germany.
Jari LahtiTurku Institute for Advanced Studies, University of Turku, Turku 20014, Finland.
Yongmei LiuDepartment of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Pedro Marques-VidalDepartment of Internal Medicine, Lausanne University Hospital (CHUV), Lausanne 1011, Switzerland.
Dan MellströmDepartment of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, Centre for Bone and Arthritis Research (CBAR), University of Gothenburg, Gothenburg 41345, Sweden.
Simon P MooijaartSection of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands.
Martina Müller-NurasyidIBE, Faculty of Medicine, Ludwig Maximilians University (LMU) Munich, Munich 81377, Germany.ORCID 0000-0003-3793-5910
Brenda PenninxDepartment of Psychiatry, Amsterdam UMC, Vrije Universiteit, Amsterdam 1081 HJ, The Netherlands.
Joana A RevezQIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.ORCID 0000-0003-3204-5396
Peter RossingSteno Diabetes Center Copenhagen, Gentofte DK2820, Denmark.
Katri RäikkönenDepartment of Psychology and Logopedics, University of Helsinki, Helsinki 00014, Finland.
Naveed SattarBHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow G12 8TA, UK.
Hubert Scharnagl66Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria.
Bengt SennbladCardiovascular Medicine, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
Angela SilveiraCardiovascular Medicine, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
Beate St PourcainMRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol BS8 2BN, UK.
Nicholas J TimpsonMRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol BS8 2BN, UK.
Julian TrollorCentre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia.
CHARGE Inflammation Working Group
Jenny van DongenDepartment of Biological Psychology, Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 BT, The Netherlands.
Diana Van HeemstBaylor College of Medicine, Houston, TX 77030, USA.
Sophie Visvikis-SiestUniversité de Lorraine, Inserm, IGE-PCV, Nancy 54000, France.
Peter VollenweiderDepartment of Internal Medicine, Lausanne University Hospital (CHUV), Lausanne 1011, Switzerland.
Uwe VölkerMediCity Research Laboratory, University of Turku, Turku 20520, Finland.
Melanie WaldenbergerInstitute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.
Gonneke WillemsenDepartment of Biological Psychology, Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 BT, The Netherlands.
Delilah ZabanehDepartment of Genetics, Environment and Evolution, University College London Genetics Institute, London WC1E 6BT, UK.
Richard W MorrisDepartment of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 1UD, UK.
Donna K ArnettDean's Office, College of Public Health, University of Kentucky, Lexington, KY 40536, USA.
Bernhard T BauneDepartment of Psychiatry, Melbourne Medical School, The University of Melbourne, Parkville 3000, Australia.
Dorret I BoomsmaDepartment of Biological Psychology, Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 BT, The Netherlands.
Yen-Pei C ChangDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD 21202, USA.
Ian J DearyCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Panos DeloukasWilliam Harvey Research Institute, Barts & the London Medical School, Queen Mary University of London, London EC1M 6BQ, UK.
Johan G ErikssonNational Institute for Health and Welfare, University of Helsinki, Helsinki 00014, Finland.
David M EvansThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland 4102, Australia.
Manuel A FerreiraQIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
Tom GauntMRC Integrative Epidemiology Unit at the University of Bristol, Bristol BS6 2BN, UK.
Vilmundur GudnasonIcelandic Heart Association, Kópavogur 201, Iceland.
Anders HamstenCardiovascular Medicine, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
Joachim HeinrichInstitute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.
Aroon HingoraniInstitute of Cardiovascular Science, University College London, London WC1E 6BT, UK.
Steve E HumphriesInstitute of Cardiovascular Science, University College London, London WC1E 6BT, UK.
J Wouter JukemaSection of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands.
Wolfgang KoenigDeutsches Herzzentrum München, Technische Universität München, Munich 80636, Germany.
Meena KumariDepartment of Epidemiology & Public Health, UCL Institute of Epidemiology & Health Care, University College London, London WC1E 7HB, UK.
Zoltan KutalikSIB Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
Deborah A LawlorMRC Integrative Epidemiology Unit at the University of Bristol, Bristol BS6 2BN, UK.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland.
Winfried MärzVth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim 68167, Germany.
Karen A MatherCentre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia.
Silvia NaitzaIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato (CA) 09042, Italy.
Matthias NauckInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
Claes OhlssonDepartment of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, Centre for Bone and Arthritis Research (CBAR), University of Gothenburg, Gothenburg 41345, Sweden.
Jackie F PriceUsher Institute, University of Edinburgh, Edinburgh EH8 9AG, UK.
Olli RaitakariCentre for Population Health Research, University of Turku, Turku University Hospital, Turku 20520, Finland.
Ken RiceDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Perminder S SachdevCentre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia.
Eline SlagboomDepartment of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
Thorkild I A SørensenNovo Nordisk Foundation Center For Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK2200, Denmark.
Tim SpectorDepartment of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.
David StaceyMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
Maria G StathopoulouUniversité de Lorraine, Inserm, IGE-PCV, Nancy 54000, France.
Toshiko TanakaLongitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224, USA.
S Goya WannametheeDepartment of Primary Care & Population Health, UCL Institute of Epidemiology & Health Care, University College London, London NW3 2PF, UK.
Peter WhincupPopulation Health Research Institute, St George's, University of London, London SW17 0RE, UK.
Jerome I RotterDepartment of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Abbas DehghanDepartment of Epidemiology, Erasmus MC, Rotterdam 3000 CA, The Netherlands.
Eric BoerwinkleHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
Harold SniederDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.
Behrooz Z AlizadehDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.

Funding

CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
Rare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6M
British Heart Foundation RG/16/11/32334British Heart Foundation RG/19/4/34452British Heart Foundation SP/13/6/30554Medical Research Council G0700704Medical Research Council G1001401Medical Research Council G9815508Medical Research Council MC_PC_15018Medical Research Council MC_PC_19009Medical Research Council MC_UU_00011/4Medical Research Council MC_UU_00011/6Medical Research Council MC_UU_12013/4Medical Research Council MR/K026992/1Medical Research Council MR/R024227/1Medical Research Council MR/S011676/1NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL120393NHLBI NIH HHS U01 HL120393Wellcome Trust 202802/Z/16/Z
6 · The paper itself

Abstract

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

Indexed as

Genome-Wide Association StudyCohort StudiesGene Expression RegulationGenetic LociGenetic Predisposition to DiseaseHLA-DRB1 ChainsHumansInterleukin-1Interleukin 1 Receptor Antagonist ProteinInterleukin-6Polymorphism, Single NucleotideReceptors, Interleukin-6White PeopleHLA-DRB1 ChainsIL1F10 protein, humanIL1RN protein, humanIL6R protein, humanInterleukin-1Interleukin 1 Receptor Antagonist ProteinInterleukin-6Receptors, Interleukin-6

Identifiers

PMID33517400
PMCPMC8098112

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