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Genome-wide association study of circulating interleukin 6 levels identifies novel loci.
Ahluwalia, Tarunveer S; Prins, Bram P; Abdollahi, Mohammadreza; Armstrong, Nicola J; Aslibekyan, Stella; Bain, Lisa; Jefferis, Barbara; Baumert, Jens; Beekman, Marian; Ben-Shlomo, Yoav; Bis, Joshua C; Mitchell, Braxton D; de Geus, Eco; Delgado, Graciela E; Marek, Diana; Eriksson, Joel; Kajantie, Eero; Kanoni, Stavroula; Kemp, John P; Lu, Chen; Marioni, Riccardo E; McLachlan, Stela; Milaneschi, Yuri; Nolte, Ilja M; Petrelis, Alexandros M; Porcu, Eleonora; Sabater-Lleal, Maria; Naderi, Elnaz; Seppälä, Ilkka; Shah, Tina; Singhal, Gaurav; Standl, Marie; Teumer, Alexander; Thalamuthu, Anbupalam; Thiering, Elisabeth; Trompet, Stella; Ballantyne, Christie M; Benjamin, Emelia J; Casas, Juan P; Toben, Catherine; Dedoussis, George; Deelen, Joris; Durda, Peter; Engmann, Jorgen; Feitosa, Mary F; Grallert, Harald; Hammarstedt, Ann; Harris, Sarah E; Homuth, Georg; Hottenga, Jouke-Jan.
Afiliação
  • Ahluwalia TS; Steno Diabetes Center Copenhagen, Gentofte DK2820, Denmark.
  • Prins BP; Department of Biology, The Bioinformatics Center, University of Copenhagen, Copenhagen DK2200, Denmark.
  • Abdollahi M; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.
  • Armstrong NJ; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.
  • Aslibekyan S; Mathematics and Statistics, Murdoch University, Perth 6150, Australia.
  • Bain L; Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, Alabama 35233, USA.
  • Jefferis B; QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
  • Baumert J; Department of Primary Care & Population Health, UCL Institute of Epidemiology & Health Care, University College London, London NW3 2PF, UK.
  • Beekman M; Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.
  • Ben-Shlomo Y; Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
  • Bis JC; Population Health Sciences, University of Bristol, Bristol BS8 2PS, UK.
  • Mitchell BD; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
  • de Geus E; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21202, USA.
  • Delgado GE; Department of Biological Psychology, Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 BT, The Netherlands.
  • Marek D; Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam 1105 AZ, The Netherlands.
  • Eriksson J; Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim 68167, Germany.
  • Kajantie E; SIB Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
  • Kanoni S; Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, Centre for Bone and Arthritis Research (CBAR), University of Gothenburg, Gothenburg 41345, Sweden.
  • Kemp JP; Chronic Disease Prevention Unit, National Institute for Health and Welfare, PO Box 30, Helsinki 00271, Finland.
  • Lu C; Hospital for Children and Adolescents, Helsinki University Central Hospital and University of Helsinki, Helsinki 00014, Finland.
  • Marioni RE; William Harvey Research Institute, Barts & the London Medical School, Queen Mary University of London, London EC1M 6BQ, UK.
  • McLachlan S; The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland 4102, Australia.
  • Milaneschi Y; MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol BS8 2BN, UK.
  • Nolte IM; Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
  • Petrelis AM; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
  • Porcu E; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Sabater-Lleal M; Usher Institute, University of Edinburgh, Edinburgh EH8 9AG, UK.
  • Naderi E; Department of Psychiatry, Amsterdam UMC, Vrije Universiteit, Amsterdam 1081 HJ, The Netherlands.
  • Seppälä I; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.
  • Shah T; Université de Lorraine, Inserm, IGE-PCV, Nancy 54000, France.
  • Singhal G; Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato (CA) 09042, Italy.
  • Standl M; Cardiovascular Medicine, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
  • Teumer A; Unit of Genomics of Complex Diseases, Institut d'Investigació Biomèdica Sant Pau (IIB-Sant Pau), Barcelona 08041, Spain.
  • Thalamuthu A; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.
  • Thiering E; Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland.
  • Trompet S; Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK.
  • Ballantyne CM; Discipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide 5005, Australia.
  • Benjamin EJ; Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.
  • Casas JP; Institute for Community Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
  • Toben C; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia.
  • Dedoussis G; Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.
  • Deelen J; Division of Metabolic Diseases and Nutritional Medicine, Ludwig-Maximilians-University of Munich, Dr. von Hauner Children's Hospital, Munich 80337, Germany.
  • Durda P; Department of Cardiology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
  • Engmann J; Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands.
  • Feitosa MF; Baylor College of Medicine, Houston, TX 77030, USA.
  • Grallert H; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA.
  • Hammarstedt A; Section of Cardiovascular Medicine and Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
  • Harris SE; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA.
  • Homuth G; Discipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide 5005, Australia.
  • Hottenga JJ; 44Department of Nutrition-Dietetics, Harokopio University, Athens 17671, Greece.
Hum Mol Genet ; 30(5): 393-409, 2021 04 27.
Article em En | MEDLINE | ID: mdl-33517400
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Interleucina-6 / Interleucina-1 / Receptores de Interleucina-6 / Proteína Antagonista do Receptor de Interleucina 1 / Estudo de Associação Genômica Ampla / Cadeias HLA-DRB1 Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Interleucina-6 / Interleucina-1 / Receptores de Interleucina-6 / Proteína Antagonista do Receptor de Interleucina 1 / Estudo de Associação Genômica Ampla / Cadeias HLA-DRB1 Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article