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

TitleGenome-wide association study of circulating interleukin 6 levels identifies novel loci.
Publication TypeJournal Article
Year of Publication2021
AuthorsAhluwalia, TS, Prins, BP, Abdollahi, M, Armstrong, NJ, Aslibekyan, S, Bain, L, Jefferis, B, Baumert, J, Beekman, M, Ben-Shlomo, Y, Bis, JC, Mitchell, BD, de Geus, E, Delgado, GE, Marek, D, Eriksson, J, Kajantie, E, Kanoni, S, Kemp, JP, Lu, C, Marioni, RE, McLachlan, S, Milaneschi, Y, Nolte, IM, Petrelis, AM, Porcu, E, Sabater-Lleal, M, Naderi, E, Seppälä, I, Shah, T, Singhal, G, Standl, M, Teumer, A, Thalamuthu, A, Thiering, E, Trompet, S, Ballantyne, CM, Benjamin, EJ, Casas, JP, Toben, C, Dedoussis, G, Deelen, J, Durda, P, Engmann, J, Feitosa, MF, Grallert, H, Hammarstedt, A, Harris, SE, Homuth, G, Hottenga, J-J, Jalkanen, S, Jamshidi, Y, Jawahar, MC, Jess, T, Kivimaki, M, Kleber, ME, Lahti, J, Liu, Y, Marques-Vidal, P, Mellström, D, Mooijaart, SP, Müller-Nurasyid, M, Penninx, B, Revez, JA, Rossing, P, Räikkönen, K, Sattar, N, Scharnagl, H, Sennblad, B, Silveira, A, St Pourcain, B, Timpson, NJ, Trollor, J, van Dongen, J, van Heemst, D, Visvikis-Siest, S, Vollenweider, P, Völker, U, Waldenberger, M, Willemsen, G, Zabaneh, D, Morris, RW, Arnett, DK, Baune, BT, Boomsma, DI, Chang, Y-PC, Deary, IJ, Deloukas, P, Eriksson, JG, Evans, DM, Ferreira, MA, Gaunt, T, Gudnason, V, Hamsten, A, Heinrich, J, Hingorani, A, Humphries, SE, J Jukema, W, Koenig, W, Kumari, M, Kutalik, Z, Lawlor, DA, Lehtimäki, T, Marz, W, Mather, KA, Naitza, S, Nauck, M, Ohlsson, C, Price, JF, Raitakari, O, Rice, K, Sachdev, PS, Slagboom, E, Sørensen, TIA, Spector, T, Stacey, D, Stathopoulou, MG, Tanaka, T, S Wannamethee, G, Whincup, P, Rotter, JI, Dehghan, A, Boerwinkle, E, Psaty, BM, Snieder, H, Alizadeh, BZ
Corporate AuthorsCHARGE Inflammation Working Group
JournalHum Mol Genet
Volume30
Issue5
Pagination393-409
Date Published2021 Apr 27
ISSN1460-2083
KeywordsCohort Studies, 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, White People
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.
DOI10.1093/hmg/ddab023
Alternate JournalHum Mol Genet
PubMed ID33517400
PubMed Central IDPMC8098112
Grant ListMC_UU_00011/4 / MRC_ / Medical Research Council / United Kingdom
MC_PC_19009 / MRC_ / Medical Research Council / United Kingdom
RG/19/4/34452 / BHF_ / British Heart Foundation / United Kingdom
U01 HL120393 / HL / NHLBI NIH HHS / United States
G0700704 / MRC_ / Medical Research Council / United Kingdom
MC_UU_00011/6 / MRC_ / Medical Research Council / United Kingdom
MR/R024227/1 / MRC_ / Medical Research Council / United Kingdom
G1001401 / MRC_ / Medical Research Council / United Kingdom
G9815508 / MRC_ / Medical Research Council / United Kingdom
MC_UU_12013/4 / MRC_ / Medical Research Council / United Kingdom
202802/Z/16/Z / WT_ / Wellcome Trust / United Kingdom
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom
RG/16/11/32334 / BHF_ / British Heart Foundation / United Kingdom
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
MC_PC_15018 / MRC_ / Medical Research Council / United Kingdom
SP/13/6/30554 / BHF_ / British Heart Foundation / United Kingdom
MR/S011676/1 / MRC_ / Medical Research Council / United Kingdom

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