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; Joshua C Bis; Braxton D Mitchell; Eco de Geus; Graciela E Delgado; Diana Marek; Joel Eriksson; Eero Kajantie; Stavroula Kanoni; John P Kemp; Chen Lu; Riccardo E Marioni; Stela McLachlan; Yuri Milaneschi; Ilja M Nolte; Alexandros M Petrelis; Eleonora Porcu; Maria Sabater-Lleal; Elnaz Naderi; Ilkka Seppälä; Tina Shah; Gaurav Singhal; Marie Standl; Alexander Teumer; Anbupalam Thalamuthu; Elisabeth Thiering; Stella Trompet; Christie M Ballantyne; Emelia J Benjamin; Juan P Casas; Catherine Toben; George Dedoussis; Joris Deelen; Peter Durda; Jorgen Engmann; Mary F Feitosa; Harald Grallert; Ann Hammarstedt; Sarah E Harris; Georg Homuth; Jouke-Jan Hottenga; Sirpa Jalkanen; Yalda Jamshidi; Magdalene C Jawahar; Tine Jess; Mika Kivimaki; Marcus E Kleber; Jari Lahti; Yongmei Liu; Pedro Marques-Vidal; Dan Mellström; Simon P Mooijaart; Martina Müller-Nurasyid; Brenda Penninx; Joana A Revez; Peter Rossing; Katri Räikkönen; Naveed Sattar; Hubert Scharnagl; Bengt Sennblad; Angela Silveira; Beate St Pourcain; Nicholas J Timpson; Julian Trollor; Jenny van Dongen; Diana Van Heemst; Sophie Visvikis-Siest; Peter Vollenweider; Uwe Völker; Melanie Waldenberger; Gonneke Willemsen; Delilah Zabaneh; Richard W Morris; Donna K Arnett; Bernhard T Baune; Dorret I Boomsma; Yen-Pei C Chang; Ian J Deary; Panos Deloukas; Johan G Eriksson; David M Evans; Manuel A Ferreira; Tom Gaunt; Vilmundur Gudnason; Anders Hamsten; Joachim Heinrich; Aroon Hingorani; Steve E Humphries; J Wouter Jukema; Wolfgang Koenig; Meena Kumari; Zoltan Kutalik; Deborah A Lawlor; Terho Lehtimäki; Winfried März; Karen A Mather; Silvia Naitza; Matthias Nauck; Claes Ohlsson; Jackie F Price; Olli Raitakari; Ken Rice; Perminder S Sachdev; Eline Slagboom; Thorkild I A Sørensen; Tim Spector; David Stacey; Maria G Stathopoulou; Toshiko Tanaka; S Goya Wannamethee; Peter Whincup; Jerome I Rotter; Abbas Dehghan; Eric Boerwinkle; Bruce M Psaty; Harold Snieder; Behrooz Z Alizadeh; CHARGE Inflammation Working Group

doi:10.1093/hmg/ddab023

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

Journal article

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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, …

Human molecular genetics, Vol.30(5), pp.393-409

27/04/2021

DOI: https://doi.org/10.1093/hmg/ddab023

PMID: 33517400

Abstract

Cohort Studies

Gene Expression Regulation

Genetic Loci

Genetic Predisposition to Disease

Genome-Wide Association Study

HLA-DRB1 Chains - genetics

Humans

Interleukin 1 Receptor Antagonist Protein - genetics

Interleukin-1 - genetics

Interleukin-6 - blood

Interleukin-6 - genetics

Polymorphism, Single Nucleotide

Receptors, Interleukin-6 - genetics

White People - genetics

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.

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Title: Genome-wide association study of circulating interleukin 6 levels identifies novel loci
Creators - without role: Tarunveer S Ahluwalia - University of Copenhagen
Bram P Prins - University Medical Center Groningen
Mohammadreza Abdollahi - University Medical Center Groningen
Nicola J Armstrong - Murdoch University
Stella Aslibekyan - University of Alabama at Birmingham
Lisa Bain - QIMR Berghofer Medical Research Institute
Barbara Jefferis - Department of Primary Care & Population Health, UCL Institute of Epidemiology & Health Care, University College London, London NW3 2PF, UK
Jens Baumert - Helmholtz Zentrum München
Marian Beekman - Leiden University Medical Center
Yoav Ben-Shlomo - University of Bristol
Joshua C Bis - University of Washington
Braxton D Mitchell - Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21202, USA
Eco de Geus - Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam 1105 AZ, The Netherlands
Graciela E Delgado - Heidelberg
Diana Marek - SIB Swiss Institute of Bioinformatics
Joel Eriksson - University of Gothenburg
Eero Kajantie - University of Helsinki
Stavroula Kanoni - Queen Mary University of London
John P Kemp - University of Bristol
Chen Lu - Boston University
Riccardo E Marioni - University of Edinburgh
Stela McLachlan - University of Edinburgh
Yuri Milaneschi - Vrije Universiteit Amsterdam
Ilja M Nolte - University Medical Center Groningen
Alexandros M Petrelis - Université de Lorraine
Eleonora Porcu - GeneTiCA
Maria Sabater-Lleal - Biomedica
Elnaz Naderi - University Medical Center Groningen
Ilkka Seppälä - Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland
Tina Shah - Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK
Gaurav Singhal - University of Adelaide
Marie Standl - Helmholtz Zentrum München
Alexander Teumer - Institute for Community Medicine, University Medicine Greifswald, Greifswald 17475, Germany
Anbupalam Thalamuthu - UNSW Sydney
Elisabeth Thiering - Division of Metabolic Diseases and Nutritional Medicine, Ludwig-Maximilians-University of Munich, Dr. von Hauner Children's Hospital, Munich 80337, Germany
Stella Trompet - Leiden University Medical Center
Christie M Ballantyne - Baylor College of Medicine
Emelia J Benjamin - Boston University School of Medicine
Juan P Casas - VA Boston Healthcare System
Catherine Toben - University of Adelaide
George Dedoussis - Harokopio University of Athens
Joris Deelen - Max Planck Institute for Biology of Ageing
Peter Durda - University of Vermont
Jorgen Engmann - Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK
Mary F Feitosa - Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110-1093, USA
Harald Grallert - German Center for Diabetes Research
Ann Hammarstedt - University of Gothenburg
Sarah E Harris - University of Edinburgh
Georg Homuth - Genomics
Jouke-Jan Hottenga - Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam 1105 AZ, The Netherlands
Sirpa Jalkanen - University of Turku
Yalda Jamshidi - St George's, University of London
Magdalene C Jawahar - University of Adelaide
Tine Jess - Veterinary Biological and Research Institute
Mika Kivimaki - Department of Epidemiology & Public Health, UCL Institute of Epidemiology & Health Care, University College London, London WC1E 7HB, UK
Marcus E Kleber - Heidelberg
Jari Lahti - University of Helsinki
Yongmei Liu - Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
Pedro Marques-Vidal - University of Lausanne
Dan Mellström - University of Gothenburg
Simon P Mooijaart - Leiden University Medical Center
Martina Müller-Nurasyid - Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johhanes Gutenberg University, Mainz 55101, Germany
Brenda Penninx - Vrije Universiteit Amsterdam
Joana A Revez - QIMR Berghofer Medical Research Institute
Peter Rossing - University of Copenhagen
Katri Räikkönen - University of Helsinki
Naveed Sattar - Faculty
Hubert Scharnagl - Medical University of Graz
Bengt Sennblad - Uppsala University
Angela Silveira - Karolinska Institutet
Beate St Pourcain - Radboud University Nijmegen
Nicholas J Timpson - University of Bristol
Julian Trollor - UNSW Sydney
Jenny van Dongen - Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam 1105 AZ, The Netherlands
Diana Van Heemst - Baylor College of Medicine
Sophie Visvikis-Siest - Université de Lorraine
Peter Vollenweider - University of Lausanne
Uwe Völker - University of Turku
Melanie Waldenberger - Helmholtz Zentrum München
Gonneke Willemsen - Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam 1105 AZ, The Netherlands
Delilah Zabaneh - Department of Genetics, Environment and Evolution, University College London Genetics Institute, London WC1E 6BT, UK
Richard W Morris - University of Bristol
Donna K Arnett - University of Kentucky
Bernhard T Baune - University of Melbourne
Dorret I Boomsma - Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam 1105 AZ, The Netherlands
Yen-Pei C Chang - Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21202, USA
Ian J Deary - University of Edinburgh
Panos Deloukas - Queen Mary University of London
Johan G Eriksson - University of Helsinki
David M Evans - University of Bristol
Manuel A Ferreira - QIMR Berghofer Medical Research Institute
Tom Gaunt - University of Bristol
Vilmundur Gudnason - University of Iceland
Anders Hamsten - Karolinska Institutet
Joachim Heinrich - University of Melbourne
Aroon Hingorani - University College London
Steve E Humphries - UCL Australia
J Wouter Jukema - Durrer Center for Cardiogenetic Research, Amsterdam 1105 AZ, The Netherlands
Wolfgang Koenig - University of Ulm
Meena Kumari - University of Essex
Zoltan Kutalik - University of Lausanne
Deborah A Lawlor - University of Bristol
Terho Lehtimäki - Tampere University
Winfried März - Synlab
Karen A Mather - Neuroscience Research Australia
Silvia Naitza - GeneTiCA
Matthias Nauck - DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald 17475, Germany
Claes Ohlsson - University of Gothenburg
Jackie F Price - University of Edinburgh
Olli Raitakari - Turku University Hospital
Ken Rice - University of Washington
Perminder S Sachdev - Neuropsychiatric Institute, Prince of Wales Hospital, Sydney 2031, Australia
Eline Slagboom - Max Planck Institute for Biology of Ageing
Thorkild I A Sørensen - University of Copenhagen
Tim Spector - King's College London
David Stacey - University of Cambridge
Maria G Stathopoulou - Université de Lorraine
Toshiko Tanaka - National Institute on Aging
S Goya Wannamethee - Department of Primary Care & Population Health, UCL Institute of Epidemiology & Health Care, University College London, London NW3 2PF, UK
Peter Whincup - St George's, University of London
Jerome I Rotter - Harbor–UCLA Medical Center
Abbas Dehghan - Erasmus MC
Eric Boerwinkle - Baylor College of Medicine
Bruce M Psaty - University of Washington
Harold Snieder - University Medical Center Groningen
Behrooz Z Alizadeh - University Medical Center Groningen
CHARGE Inflammation Working Group
Publication Details: Human molecular genetics, Vol.30(5), pp.393-409
Grant note: MR/R024227/1 / Medical Research Council MC_UU_00011/4 / Medical Research Council R01 HL120393 / NHLBI NIH HHS U01 HL120393 / NHLBI NIH HHS RG/19/4/34452 / British Heart Foundation G1001401 / Medical Research Council RG/16/11/32334 / British Heart Foundation R01 HL105756 / NHLBI NIH HHS G0700704 / Medical Research Council MC_UU_00011/6 / Medical Research Council SP/13/6/30554 / British Heart Foundation 202802/Z/16/Z / Wellcome Trust MR/K026992/1 / Medical Research Council G9815508 / Medical Research Council MC_PC_15018 / Medical Research Council MC_PC_19009 / Medical Research Council MC_UU_12013/4 / Medical Research Council MR/S011676/1 / Medical Research Council
Identifiers: 9937405608331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article