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Ahluwalia, T.S.* ; Prins, B.P.* ; Abdollahi, M.* ; Armstrong, N.J.* ; Aslibekyan, S.* ; Bain, L.* ; Jefferis, B.* ; Baumert, J.J. ; Beekman, M.* ; Ben-Shlomo, Y.* ; Bis, J.C.* ; Mitchell, B.D.* ; de Geus, E.* ; Delgado, G.E.* ; Marek, D.* ; Eriksson, J.* ; Kajantie, E.* ; Kanoni, S.* ; Kemp, J.P.* ; Lu, C.* ; Marioni, R.E.* ; McLachlan, S.* ; Milaneschi, Y.* ; Nolte, I.M.* ; Petrelis, A.M.* ; Porcu, E.* ; Sabater-Lleal, M.* ; Naderi, E.* ; Seppälä, I.* ; Shah, T.* ; Singhal, G.* ; Standl, M. ; Teumer, A.* ; Thalamuthu, A.* ; Thiering, E. ; Trompet, S.* ; Ballantyne, C.M.* ; Benjamin, E.J.* ; Casas, J.P.* ; Toben, C.* ; Dedoussis, G.* ; Deelen, J.* ; Durda, P.* ; Engmann, J.* ; Feitosa, M.F.* ; Grallert, H. ; Hammarstedt, A.* ; Harris, S.E.* ; Homuth, G.* ; Hottenga, J.J.* ; Jalkanen, S.* ; Jamshidi, Y.* ; Jawahar, M.C.* ; Jess, T.* ; Kivimaki, M.* ; Kleber, M.E.* ; Lahti, J.* ; Liu, Y.* ; Marques-Vidal, P.* ; Mellström, D.* ; Mooijaart, S.P.* ; Müller-Nurasyid, M. ; Penninx, B.* ; Revez, J.A.* ; Rossing, P.* ; Räikkönen, K.* ; Sattar, N.* ; Scharnagl, H.* ; Sennblad, B.* ; Silveira, A.* ; Pourcain, B.S.* ; Timpson, N.J.* ; Trollor, J.* ; van Dongen, J.* ; van Heemst, D.* ; Visvikis-Siest, S.* ; Vollenweider, P.* ; Völker, U.* ; Waldenberger, M. ; Willemsen, G.* ; Zabaneh, D.* ; Morris, R.W.* ; Arnett, D.K.* ; Baune, B.T.* ; Boomsma, D.I.* ; Chang, Y.C.* ; Deary, I.J.* ; Deloukas, P.* ; Eriksson, J.G.* ; Evans, D.M* ; Ferreira, M.A.* ; Gaunt, T.* ; Gudnason, V.* ; Hamsten, A.* ; Heinrich, J. ; Hingorani, A.* ; Humphries, S.E.* ; Jukema, J.W.* ; Koeing, W.* ; Kumari, M.* ; Kutalik, Z.* ; Lawlor, D.A.* ; Lehtimäki, T.* ; März, W.* ; Mather, K.* ; Naitza, S.* ; Nauck, M.* ; Ohlsson, C.* ; Price, J.F.* ; Raitakari, O.* ; Rice, K.* ; Sachdev, P.S.* ; Slagboom, E.* ; Sørensen, T.I.A.* ; Spector, T.* ; Stacey, D.* ; Stathopoulou, M.G.* ; Tanaka, T.* ; Wannamethee, S.G.* ; Whincup, P.* ; Rotter, J.I.* ; Dehghan, A.* ; Boerwinkle, E.* ; Psaty, B.M.* ; Snieder, H.* ; Alizadeh, B.Z.*

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

Hum. Mol. Genet. 30, 393-409 (2021)
Publ. Version/Full Text Postprint DOI PMC
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords C-reactive Protein; Systemic-lupus-erythematosus; Receptor Il-6r Gene; Susceptibility Loci; Rheumatoid-arthritis; Chronic Inflammation; Produce Il-6; Disease; Cells; Architecture
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Journal Human Molecular Genetics
Quellenangaben Volume: 30, Issue: 5, Pages: 393-409 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Great Clarendon St, Oxford Ox2 6dp, England
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
POF-Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504000-008
G-504091-002
G-504100-001
G-504091-001
Grants Novo Nordisk Foundation
DOI 10.1093/hmg/ddab023
WOS ID WOS:000654638100007
Scopus ID 85106143662
PubMed ID 33517400
Erfassungsdatum 2021-04-13
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