Genome-wide association study of circulating interleukin 6 levels identifies novel loci
Ahluwalia, Tarunveer Singh (University of Copenhagen)
Prins, Bram Peter (University of Groningen)
Abdollahi, Mohammadreza (University of Groningen)
Armstrong, Nicola (Murdoch University)
Aslibekyan, Stella (University of Alabama at Birmingham School of Public Health)
Bain, Lisa J (Qimr Berghofer Medical Research Institute)
Jefferis, Barbara (University College London)
Baumert, Jens (Helmholtz Zentrum München-German Research Center for Environmental Health)
Beekman, Marian (Leiden University Medical Center)
Ben-Shlomo, Yoav (University of Bristol)
Bis, Joshua C (University of Washington)
Mitchell, Braxton D. (University of Maryland School of Medicine)
de Geus, Eco J. C (Amsterdam UMC. University Medical Center)
Delgado, Graciela E. (University of Heidelberg)
Marek, Diana (Sib Swiss Institute of Bioinformatics)
Eriksson, Joel (University of Gothenburg)
Kajantie, Eero (Helsinki University Central Hospital and University of Helsinki)
Kanoni, Stavroula (Queen Mary University of London)
Kemp, John P. (University of Bristol)
Lu, Chen (Boston University School of Public Health)
Marioni, Riccardo E. (University of Edinburgh)
McLachlan, Stela (University of Edinburgh)
Milaneschi, Yuri (Amsterdam Umc. Vrije Universiteit)
Nolte, Ilja M. (University of Groningen)
Petrelis, Alexandros M. (Université de Lorraine)
Porcu, Eleonora (Consiglio Nazionale Delle Ricerche)
Sabater-Lleal, Maria (Institut d'Investigació Biomèdica Sant Pau)
Naderi, Elnaz (University of Groningen)
Seppälä, Ilkka (Tampere University)
Shah, Tina (University College London)
Singhal, Gaurav (University of Adelaide)
Standl, Marie (Helmholtz Zentrum München-German Research Center for Environmental Health)
Teumer, Alexander (University Medicine Greifswald)
Thalamuthu, Anbupalam (University of New South Wales)
Thiering, Elisabeth (Ludwig-Maximilians-University of Munich. Dr. von Hauner Children's Hospital)
Trompet, Stella (Leiden University Medical Center)
Ballantyne, Christie M. (Baylor College of Medicine)
Benjamin, Emelia J. (Boston University School of Medicine)
Casas, Juan P. (Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). Va Boston Healthcare System)
Toben, Catherine (University of Adelaide)
Dedoussis, George (Harokopio University)
Deelen, Joris (Max Planck Institute for Biology of Ageing)
Durda, Peter (Larner College of Medicine. University of Vermont)
Engmann, Jorgen (University College London)
Feitosa, Mary (Washington University School of Medicine)
Grallert, Harald (German Center for Diabetes Research (DZD))
Hammarstedt, Ann (Sahlgrenska Academy at the University of Gothenburg)
Harris, Sarah E (University of Edinburgh)
Homuth, Georg (University Medicine Greifswald)
Hottenga, Jouke Jan (Amsterdam UMC. University Medical Center)
Jalkanen, Sirpa (University of Turku)
Jamshidi, Yalda (St George's University of London)
Jawahar, Magdalene C. (University of Adelaide)
Jess, Tine (Statens Serum Institute)
Kivimaki, Mika (University College London)
Kleber, Marcus E. (University of Heidelberg)
Lahti, Jari (University of Helsinki)
Liu, Yongmei (Wake Forest School of Medicine)
Marques-Vidal, Pedro (University of Lausanne)
Mellström, Dan (Sahlgrenska Academy at the University of Gothenburg. Centre for Bone and Arthritis Research)
Mooijaart, Simon P. (Leiden University Medical Center)
Müller-Nurasyid, Martina (Johhanes Gutenberg University)
Penninx, Brenda WJH (Amsterdam Umc. Vrije Universiteit)
Revez, Joana A. (Qimr Berghofer Medical Research Institute)
Rossing, Peter (University of Copenhagen)
Raïkkönen, Katri (University of Helsinki)
Sattar, Naveed (Bhf Glasgow Cardiovascular Research Centre)
Scharnagl, Hubert (Medical University of Graz)
Sennblad, Bengt (Uppsala University)
Silveira, Angela (Karolinska Institutet (Estocolm, Suècia))
Pourcain, Beate St (Radboud University)
Timpson, Nicholas J. (University of Bristol)
Trollor, Julian (University of New South Wales)
Van Dongen, Jenny (Amsterdam UMC. University Medical Center)
Van Heemst, Diana (Baylor College of Medicine)
Visvikis-Siest, Sophie (Université de Lorraine. Inserm. IGE-PCV)
Vollenweider, Peter (University of Lausanne)
Völker, Uwe (University of Turku)
Waldenberger, Melanie (Helmholtz Zentrum München-German Research Center for Environmental Health)
Willemsen, Gonneke (Amsterdam UMC. University Medical Center)
Zabaneh, Delilah (University College London Genetics Institute)
Morris, Richard W. (Bristol Medical School. University of Bristol)
Arnett, Donna K. (University of Kentucky)
Baune, Bernhard T. (University of Melbourne)
Boomsma, Dorret I. (Amsterdam UMC. University Medical Center)
Chang, Yen-Pei C. (University of Maryland School of Medicine)
Deary, Ian J. (University of Edinburgh)
Deloukas, Panos (Queen Mary University of London)
Eriksson, Johan G. (University of Helsinki)
Evans, David M. (University of Bristol)
Ferreira, Manuel A. (Qimr Berghofer Medical Research Institute)
Gaunt, Tom (University of Bristol)
Gudnason, Vilmundur (University of Iceland)
Hamsten, Anders (Karolinska Institutet (Estocolm, Suècia))
Heinrich, Joachim (University of Melbourne)
Hingorani, Aroon (University College London)
Humphries, Steve E. (University College London)
Jukema, J. Wouter (Durrer Center for Cardiogenetic Research)
Koenig, Wolfgang (University of Ulm)
Kumari, Meena (University of Essex)
Kutalik, Zoltan (University of Lausanne)
Lawlor, Deborah A. (University of Bristol)
Lehtimäki, Terho (Tampere University)
März, Winfried (Synlab Academy. Synalb Holding Deutschland GmbH)
Mather, Karen A (Neuroscience Research Australia)
Naitza, Silvia. (Consiglio Nazionale Delle Ricerche)
Nauck, Matthias (Dzhk (German Center for Cardiovascular Research). Partner Site Greifswald)
Ohlsson, Claes (University of Gothenburg)
Price, Jackie F. (University of Edinburgh)
Raitakari, Olli (Turku University Hospital (Finlàndia))
Rice, Ken (University of Washington)
Sachdev, Perminder S. (Prince of Wales Hospital (Australia))
Slagboom, Pieternella Eline (Max Planck Institute for Biology of Ageing)
Sørensen, Thorkild I.A. (University of Copenhagen. Department of Public Health. Section on Epidemiology)
Spector, Tim (King's College London. Department of Twin Research and Genetic Epidemiology)
Stacey, David (University of Cambridge)
Stathopoulou, Maria G. (Université de Lorraine. Inserm. IGE-PCV)
Tanaka, Toshiko (National Institute on Aging (Estats Units d'Amèrica))
Wannamethee, Sasiwarang Goya (University College London)
Whincup, Peter (University of London)
Rotter, Jerome I. (The Lundquist Institute at Harbor-UCLA Medical Center)
Dehghan, Abbas (Erasmus Mc)
Boerwinkle, Eric (Baylor College of Medicine)
Psaty, Bruce M. (University of Washington)
Snieder, Harold (University Medical Center Groningen)
Alizadeh, Behrooz Ziad (University Medical Center Groningen)

Data:	2021
Resum:	Interleukin 6 (IL-6) is a multifunctional cytokine with both pro-A nd 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.
Nota:	Altres ajuts: Novo Nordisk Foundation (NNF18OC0052457).
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cohort Studies ; European Continental Ancestry Group ; Gene Expression Regulation ; Genetic Loci ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; HLA-DRB1 Chains ; Humans ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-1 ; Interleukin-6 ; Polymorphism, Single Nucleotide ; Receptors, Interleukin-6
Publicat a:	Human Molecular Genetics, Vol. 30 Núm. 5 (january 2021) , p. 393-409, ISSN 1460-2083

DOI: 10.1093/hmg/ddab023
PMID: 33517400

17 p, 1.3 MB

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