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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
Open Access Hybrid
Creative Commons Lizenzvertrag
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
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)
Grants Novo Nordisk Foundation