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

Ahluwalia, T. S., Prins, B. P., Abdollahi, M., Armstrong, N. J., Aslibekyan, S., Bain, L., et al. (2021). Genome-wide association study of circulating interleukin 6 levels identifies novel loci. Human Molecular Genetics, 5(1), 393-409. doi:10.1093/hmg/ddab023.

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Datensatz-Permalink: https://hdl.handle.net/21.11116/0000-0008-A460-2 Versions-Permalink: https://hdl.handle.net/21.11116/0000-0009-81D7-2
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© The Author(s) 2021.Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse,distribution,and reproduction in any medium,provided the original work is properly cited.
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 Urheber:
Ahluwalia, Tarunveer S.1, 2, Autor
Prins, Bram P.3, Autor
Abdollahi, Mohammadreza3, Autor
Armstrong, Nicola J.4, Autor
Aslibekyan, Stella5, Autor
Bain, Lisa6, Autor
Jefferis, Barbara7, Autor
Baumert, Jens8, Autor
Beekman, Marian9, Autor
Ben-Shlomo, Yoav10, Autor
Bis, Joshua C.11, Autor
Mitchell, Braxton D.12, Autor
De Geus, Eco13, 14, Autor
Delgado, Graciela E.15, Autor
Marek, Diana16, Autor
Eriksson, Joel17, Autor
Kajantie, Eero18, 19, Autor
Kanoni, Stavroula20, Autor
Kemp, John P.10, 21, Autor
Lu, Chen22, Autor
Marioni, Riccardo E.23, AutorMcLachlan, Stela23, AutorMilaneschi, Yuri24, AutorNolte, Ilja M.3, AutorPetrelis, Alexandros M.25, AutorPorcu, Eleonora26, AutorSabater-Lleal, Maria27, 28, AutorNaderi, Elnaz3, AutorSeppälä, Ilkka29, AutorShah, Tina7, AutorSinghal, Gaurav30, AutorStandl, Marie8, AutorTeumer, Alexander31, AutorThalamuthu, Anbupalam32, AutorThiering, Elisabeth8, 33, AutorTrompet, Stella9, AutorBallantyne, Christie M.34, AutorBenjamin, Emelia J.35, AutorCasas, Juan P.36, AutorToben, Catherine30, AutorDedoussis, George37, AutorDeelen, Joris9, 38, AutorDurda, Peter39, AutorEngmann, Jorgen7, AutorFeitosa, Mary F.40, AutorGrallert, Harald8, 41, AutorHammarstedt, Ann42, AutorHarris, Sarah E.23, AutorHomuth, Georg31, AutorHottenga, Jouke-Jan13, 14, AutorJalkanen, Sirpa43, AutorJamshidi, Yalda44, AutorJawahar, Magdalene C.30, AutorJess, Tine45, AutorKivimaki, Mika7, AutorKleber, Marcus E.15, AutorLahti, Jari43, 46, AutorLiu, Yongmei47, AutorMarques-Vidal, Pedro48, 49, AutorMellström, Dan17, AutorMooijaart, Simon P.9, AutorMüller-Nurasyid, Martina33, 50, AutorPenninx, Brenda24, AutorRevez, Joana A.6, AutorRossing, Peter1, 2, AutorRäikkönen, Katri46, AutorSattar, Naveed51, AutorScharnagl, Hubert52, AutorSennblad, Bengt27, 53, AutorSilveira, Angela27, AutorSt Pourcain, Beate10, 54, 55, 56, Autor           Timpson, Nicholas J.10, AutorTrollor, Julian32, AutorCHARGE Inflammation Working Group, Autor              Van Dongen, Jenny13, 14, AutorVan Heemst, Diana 34, AutorVisvikis-Siest, Sophie25, AutorVollenweider, Peter48, 49, AutorVölker, Uwe43, AutorWaldenberger, Melanie8, AutorWillemsen, Gonneke13, 14, AutorZabaneh, Delilah7, AutorMorris, Richard W.57, AutorArnett, Donna K.58, AutorBaune, Bernhard T.59, 60, AutorBoomsma, Dorret I.13, 14, AutorChang, Yen-Pei C.12, AutorDeary, Ian J.23, AutorDeloukas, Panos20, AutorEriksson, Johan G.46, AutorEvans, David M.10, 21, AutorFerreira, Manuel A.6, AutorGaunt, Tom10, AutorGudnason, Vilmundur61, 62, AutorHamsten, Anders27, AutorHeinrich, Joachim8, 33, 59, AutorHingorani, Aroon7, AutorHumphries, Steve E.7, AutorJukema, J. Wouter9, 63, AutorKoenig, Wolfgang64, 65, 66, AutorKumari, Meena7, 67, AutorKutalik, Zoltan16, 49, AutorLawlor, Deborah A.10, AutorLehtimäki, Terho29, AutorMärz, Winfried15, 52, 68, AutorMather, Karen A.32, 69, AutorNaitza, Silvia26, AutorNauck, Matthias31, 65, AutorOhlsson, Claes17, AutorPrice, Jackie F.23, AutorRaitakari, Olli43, AutorRice, Ken11, AutorSachdev, Perminder S.32, 70, AutorSlagboom, Eline9, 38, AutorSørensen, Thorkild I. A.2, AutorSpector, Tim71, AutorStacey, David72, AutorStathopoulou, Maria G.25, AutorTanaka, Toshiko73, AutorWannamethee, S. Goya7, AutorWhincup, Peter44, AutorRotter, Jerome I.74, AutorDehghan, Abbas75, AutorBoerwinkle, Eric34, 76, AutorPsaty, Bruce M.11, AutorSnieder, Harold3, AutorAlizadeh, Behrooz Z.3, Autor mehr..
Affiliations:
1Steno Diabetes Center Copenhagen, Gentofte, Denmark, ou_persistent22              
2University of Copenhagen, Copenhagen, Denmark, ou_persistent22              
3University of Groningen, University Medical Center Groningen, Groningen, The Netherlands, ou_persistent22              
4Murdoch University, Perth, Australia, ou_persistent22              
5University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA, ou_persistent22              
6QIMR Berghofer Medical Research Institute, Brisbane, Australia, ou_persistent22              
7University College London, London, UK, ou_persistent22              
8Helmholtz Zentrum München, Neuherberg, Germany, ou_persistent22              
9Leiden University Medical Center, Leiden, The Netherlands, ou_persistent22              
10University of Bristol, Bristol, UK, ou_persistent22              
11University of Washington, Seattle, WA, USA, ou_persistent22              
12University of Maryland School of Medicine, Baltimore, MD, USA, ou_persistent22              
13Vrije Universiteit Amsterdam, Amsterdam, The Netherlands, ou_persistent22              
14Amsterdam University Medical Center, Amsterdam, The Netherlands, ou_persistent22              
15Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany, ou_persistent22              
16SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland, ou_persistent22              
17University of Gothenburg, Gothenburg, Sweden, ou_persistent22              
18National Institute for Health and Welfare, Helsinki, Finland, ou_persistent22              
19Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland, ou_persistent22              
20Queen Mary University of London , London, UK, ou_persistent22              
21The University of Queensland, Woolloongabb, Australia, ou_persistent22              
22Boston University School of Public Health, Boston, MA, USA, ou_persistent22              
23University of Edinburgh, Edinburgh, UK, ou_persistent22              
24Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands, ou_persistent22              
25Université de Lorraine, Nancy, France, ou_persistent22              
26Consiglio Nazionale delle Ricerche, Monserrato, Italy, ou_persistent22              
27Karolinska Institutet, Stockholm, Sweden, ou_persistent22              
28Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain, ou_persistent22              
29Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland, ou_persistent22              
30Adelaide Medical School, University of Adelaide, Adelaide, Australia, ou_persistent22              
31University Medicine Greifswald, Greifswald, Germany, ou_persistent22              
32University of New South Wales, Sydney, Australia, ou_persistent22              
33Ludwig-Maximilians-University of Munich, Munich, Germany, ou_persistent22              
34Baylor College of Medicine, Houston, TX, USA, ou_persistent22              
35Boston University School of Medicine, Boston, MA, USA, ou_persistent22              
36VA Boston Healthcare System, Boston, MA, USA, ou_persistent22              
37Harokopio University, Athens, Greece, ou_persistent22              
38Max Planck Institute for Biology of Ageing, Cologne, Germany, ou_persistent22              
39University of Vermont, Burlington, VT, USA , ou_persistent22              
40Washington University School of Medicine, St. Louis, MO, USA, ou_persistent22              
41German Center for Diabetes Research (DZD) , Neuherberg, Germany, ou_persistent22              
42Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden, ou_persistent22              
43University of Turku, Turku, Finland, ou_persistent22              
44St George’s University of London, London, UK, ou_persistent22              
45Statens Serum Institute, Copenhagen, Denmark, ou_persistent22              
46University of Helsinki, Helsinki, Finland, ou_persistent22              
47Wake Forest School of Medicine, Winston-Salem, NC, USA, ou_persistent22              
48Lausanne University Hospital (CHUV), Lausanne, Switzerland, ou_persistent22              
49University of Lausanne, Lausanne, Switzerland, ou_persistent22              
50University Medical Center, Johhanes Gutenberg University, Mainz, Germany, ou_persistent22              
51University of Glasgow, Faculty of Medicine, Glasgow, UK, ou_persistent22              
52Medical University of Graz, Graz, Austria, ou_persistent22              
53Uppsala University, Uppsala, Sweden, ou_persistent22              
54Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society, ou_792549              
55Donders Institute for Brain, Cognition and Behaviour, External Organizations, ou_55236              
56Population genetics of human communication, MPI for Psycholinguistics, Max Planck Society, Wundtlaan 1, 6525 XD Nijmegen, NL, ou_2579694              
57Bristol Medical School, University of Bristol, Bristol, UK, ou_persistent22              
58University of Kentucky, Lexington, Lexington, KY, UK, ou_persistent22              
59The University of Melbourne, Parkville, Australia, ou_persistent22              
60University of Muenster, Muenster, Germany, ou_persistent22              
61Icelandic Heart Association, Kópavogur, Iceland, ou_persistent22              
62Faculty of Medicine, University of Iceland, Reykjavik, Iceland, ou_persistent22              
63Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands, ou_persistent22              
64Technische Universität München, Munich, Germany, ou_persistent22              
65DZHK (German Centre for Cardiovascular Research), Munich, Germany, ou_persistent22              
66University of Ulm, Ulm, Germany, ou_persistent22              
67University of Essex, Colchester, UK, ou_persistent22              
68SYNALB Holding Deutschland Gmb, Mannheim, Germany, ou_persistent22              
69Neuroscience Research Australia, Sydney, Australia, ou_persistent22              
70Prince of Wales Hospital, Sydney, Australia, ou_persistent22              
71King’s College London, London, UK, ou_persistent22              
72University of Cambridge, Cambridge, UK, ou_persistent22              
73National Institute on Aging, Baltimore, MD, USA, ou_persistent22              
74UCLA Medical Center, Torrance, CA, USA, ou_persistent22              
75Erasmus MC, Rotterdam, The Netherlands, ou_persistent22              
76University of Texas Health Science Center at Houston, Houston, TX, USA, ou_persistent22              

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 Zusammenfassung: 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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Sprache(n): eng - English
 Datum: 2021-03
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1093/hmg/ddab023
 Art des Abschluß: -

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Titel: Human Molecular Genetics
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Oxford, England : IRL Press
Seiten: - Band / Heft: 5 (1) Artikelnummer: - Start- / Endseite: 393 - 409 Identifikator: ISSN: 0964-6906
CoNE: https://pure.mpg.de/cone/journals/resource/954925581153