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

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dc.contributor.authorAhluwalia, Tarunveer S.
dc.contributor.authorPrins, Bram P.
dc.contributor.authorAbdollahi, Mohammadreza
dc.contributor.authorArmstrong, Nicola J.
dc.contributor.authorAslibekyan, Stella
dc.contributor.authorBain, Lisa
dc.contributor.authorJefferis, Barbara
dc.contributor.authorBaumert, Jens
dc.contributor.authorBeekman, Marian
dc.contributor.authorBen-Shlomo, Yoav
dc.contributor.authorBis, Joshua C.
dc.contributor.authorMitchell, Braxton D.
dc.contributor.authorDe Geus, Eco
dc.contributor.authorDelgado, Graciela E.
dc.contributor.authorMarek, Diana
dc.contributor.authorEriksson, Joel
dc.contributor.authorKajantie, Eero
dc.contributor.authorKanoni, Stavroula
dc.contributor.authorKemp, John P.
dc.contributor.authorLu, Chen
dc.contributor.authorMarioni, Riccardo E.
dc.contributor.authorMcLachlan, Stela
dc.contributor.authorMilaneschi, Yuri
dc.contributor.authorNolte, Ilja M.
dc.contributor.authorPetrelis, Alexandros M.
dc.contributor.authorPorcu, Eleonora
dc.contributor.authorSabater-Lleal, Maria
dc.contributor.authorNaderi, Elnaz
dc.contributor.authorSeppälä, Ilkka
dc.contributor.authorShah, Tina
dc.contributor.authorSinghal, Gaurav
dc.contributor.authorStandl, Marie
dc.contributor.authorTeumer, Alexander
dc.contributor.authorThalamuthu, Anbupalam
dc.contributor.authorThiering, Elisabeth
dc.contributor.authorTrompet, Stella
dc.contributor.authorBallantyne, Christie M.
dc.contributor.authorBenjamin, Emelia J.
dc.contributor.authorCasas, Juan P.
dc.contributor.authorToben, Catherine
dc.contributor.authorDedoussis, George
dc.contributor.authorDeelen, Joris
dc.contributor.authorDurda, Peter
dc.contributor.authorEngmann, Jorgen
dc.contributor.authorFeitosa, Mary F.
dc.contributor.authorGrallert, Harald
dc.contributor.authorHammarstedt, Ann
dc.contributor.authorHarris, Sarah E.
dc.contributor.authorHomuth, Georg
dc.contributor.authorGuðnason, Vilmundur G.
dc.contributor.departmentFaculty of Medicine
dc.date.accessioned2025-11-20T08:18:01Z
dc.date.available2025-11-20T08:18:01Z
dc.date.issued2021-01-30
dc.descriptionFunding 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.en
dc.description.abstractInterleukin 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.en
dc.description.versionPeer revieweden
dc.format.extent17
dc.format.extent1381772
dc.format.extent393-409
dc.identifier.citationAhluwalia, 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/ddab023en
dc.identifier.doi10.1093/hmg/ddab023
dc.identifier.issn0964-6906
dc.identifier.other35633518
dc.identifier.other0d4ddb7a-ee79-4625-aefd-bb05ff1c4c9d
dc.identifier.other85106143662
dc.identifier.other33517400
dc.identifier.otherunpaywall: 10.1093/hmg/ddab023
dc.identifier.urihttps://hdl.handle.net/20.500.11815/6250
dc.language.isoen
dc.relation.ispartofseriesHuman Molecular Genetics; 30(5)en
dc.relation.urlhttps://www.scopus.com/pages/publications/85106143662en
dc.rightsinfo:eu-repo/semantics/openAccessen
dc.subjectCohort Studiesen
dc.subjectGene Expression Regulationen
dc.subjectGenetic Locien
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectGenome-Wide Association Studyen
dc.subjectHLA-DRB1 Chains/geneticsen
dc.subjectHumansen
dc.subjectInterleukin 1 Receptor Antagonist Protein/geneticsen
dc.subjectInterleukin-1/geneticsen
dc.subjectInterleukin-6/blooden
dc.subjectPolymorphism, Single Nucleotideen
dc.subjectReceptors, Interleukin-6/geneticsen
dc.subjectWhites/geneticsen
dc.subjectGenetics (clinical)en
dc.subjectGeneticsen
dc.subjectMolecular Biologyen
dc.titleGenome-wide association study of circulating interleukin 6 levels identifies novel locien
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/articleen

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