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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Ahluwalia, 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; Pourcain, BS; Timpson, NJ; Trollor, J; CHARGE Inflammation Working Group, ; 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; Jukema, JW; Koenig, W; Kumari, M; Kutalik, Z; Lawlor, DA; Lehtimäki, T; März, 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; Wannamethee, SG; Whincup, P; Rotter, JI; Dehghan, A; Boerwinkle, E; Psaty, BM; Snieder, H; Alizadeh, BZ

Published Date

  • April 27, 2021

Published In

Volume / Issue

  • 30 / 5

Start / End Page

  • 393 - 409

PubMed ID

  • 33517400

Pubmed Central ID

  • PMC8098112

Electronic International Standard Serial Number (EISSN)

  • 1460-2083

Digital Object Identifier (DOI)

  • 10.1093/hmg/ddab023


  • eng

Conference Location

  • England