Ahluwalia, Tarunveer S.Prins, Bram P.Abdollahi, MohammadrezaArmstrong, Nicola J.Aslibekyan, StellaBain, LisaJefferis, BarbaraBaumert, JensBeekman, MarianBen-Shlomo, YoavBis, Joshua C.Mitchell, Braxton D.De Geus, EcoDelgado, Graciela E.Marek, DianaEriksson, JoelKajantie, EeroKanoni, StavroulaKemp, John P.Lu, ChenMarioni, Riccardo E.McLachlan, StelaMilaneschi, YuriNolte, Ilja M.Petrelis, Alexandros M.Porcu, EleonoraSabater-Lleal, MariaNaderi, ElnazSeppälä, IlkkaShah, TinaSinghal, GauravStandl, MarieTeumer, AlexanderThalamuthu, AnbupalamThiering, ElisabethTrompet, StellaBallantyne, Christie M.Benjamin, Emelia J.Casas, Juan P.Toben, CatherineDedoussis, GeorgeDeelen, JorisDurda, PeterEngmann, JorgenFeitosa, Mary F.Grallert, HaraldHammarstedt, AnnHarris, Sarah E.Homuth, GeorgGuðnason, Vilmundur G.2025-11-202025-11-202021-01-30Ahluwalia, T S, Prins, B P, Abdollahi, M, Armstrong, N J, Aslibekyan, S, Bain, L, Jefferis, B, Baumert, 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 & Guðnason, V G 2021, 'Genome-wide association study of circulating interleukin 6 levels identifies novel loci', Human Molecular Genetics, vol. 30, no. 5, pp. 393-409. https://doi.org/10.1093/hmg/ddab0230964-6906356335180d4ddb7a-ee79-4625-aefd-bb05ff1c4c9d8510614366233517400unpaywall: 10.1093/hmg/ddab023https://hdl.handle.net/20.500.11815/6250Funding Novo Nordisk Foundation (NNF18OC0052457 to T.S.A.). Detailed Funding statements from participating study cohorts can be found in Supplementary Material, Table S12. Publisher Copyright: © The Author(s) 2021. Published by Oxford University Press.Interleukin 6 (IL-6) is a multifunctional cytokine with both pro-A nd 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.171381772393-409eninfo:eu-repo/semantics/openAccessCohort StudiesGene Expression RegulationGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHLA-DRB1 Chains/geneticsHumansInterleukin 1 Receptor Antagonist Protein/geneticsInterleukin-1/geneticsInterleukin-6/bloodPolymorphism, Single NucleotideReceptors, Interleukin-6/geneticsWhites/geneticsGenetics (clinical)GeneticsMolecular Biology/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article10.1093/hmg/ddab023