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

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dc.contributor.author Ahluwalia, Tarunveer S.
dc.contributor.author Prins, Bram P.
dc.contributor.author Abdollahi, Mohammadreza
dc.contributor.author Armstrong, Nicola J.
dc.contributor.author Aslibekyan, Stella
dc.contributor.author Bain, Lisa
dc.contributor.author Jefferis, Barbara
dc.contributor.author Baumert, Jens
dc.contributor.author Beekman, Marian
dc.contributor.author Ben-Shlomo, Yoav
dc.contributor.author Bis, Joshua C.
dc.contributor.author Mitchell, Braxton D.
dc.contributor.author De Geus, Eco
dc.contributor.author Delgado, Graciela E.
dc.contributor.author Marek, Diana
dc.contributor.author Eriksson, Joel
dc.contributor.author Kajantie, Eero
dc.contributor.author Kanoni, Stavroula
dc.contributor.author Kemp, John P.
dc.contributor.author Lu, Chen
dc.contributor.author Marioni, Riccardo E.
dc.contributor.author McLachlan, Stela
dc.contributor.author Milaneschi, Yuri
dc.contributor.author Nolte, Ilja M.
dc.contributor.author Petrelis, Alexandros M.
dc.contributor.author Porcu, Eleonora
dc.contributor.author Sabater-Lleal, Maria
dc.contributor.author Naderi, Elnaz
dc.contributor.author Seppälä, Ilkka
dc.contributor.author Shah, Tina
dc.contributor.author Singhal, Gaurav
dc.contributor.author Standl, Marie
dc.contributor.author Teumer, Alexander
dc.contributor.author Thalamuthu, Anbupalam
dc.contributor.author Thiering, Elisabeth
dc.contributor.author Trompet, Stella
dc.contributor.author Ballantyne, Christie M.
dc.contributor.author Benjamin, Emelia J.
dc.contributor.author Casas, Juan P.
dc.contributor.author Toben, Catherine
dc.contributor.author Dedoussis, George
dc.contributor.author Deelen, Joris
dc.contributor.author Durda, Peter
dc.contributor.author Engmann, Jorgen
dc.contributor.author Feitosa, Mary F.
dc.contributor.author Grallert, Harald
dc.contributor.author Hammarstedt, Ann
dc.contributor.author Harris, Sarah E.
dc.contributor.author Homuth, Georg
dc.contributor.author Guðnason, Vilmundur G.
dc.date.accessioned 2022-05-05T01:01:59Z
dc.date.available 2022-05-05T01:01:59Z
dc.date.issued 2021-01-30
dc.identifier.citation Ahluwalia , 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/ddab023
dc.identifier.issn 0964-6906
dc.identifier.other 35633518
dc.identifier.other 0d4ddb7a-ee79-4625-aefd-bb05ff1c4c9d
dc.identifier.other 85106143662
dc.identifier.other 33517400
dc.identifier.other unpaywall: 10.1093/hmg/ddab023
dc.identifier.uri https://hdl.handle.net/20.500.11815/3131
dc.description Funding 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.
dc.description.abstract 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.
dc.format.extent 17
dc.format.extent 1381772
dc.format.extent 393-409
dc.language.iso en
dc.relation.ispartofseries Human Molecular Genetics; 30(5)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Ónæmisfræði
dc.subject Erfðafræði
dc.subject Sameindalíffræði
dc.subject Cohort Studies
dc.subject Gene Expression Regulation
dc.subject Genetic Loci
dc.subject Genetic Predisposition to Disease
dc.subject Genome-Wide Association Study
dc.subject HLA-DRB1 Chains/genetics
dc.subject Humans
dc.subject Interleukin 1 Receptor Antagonist Protein/genetics
dc.subject Interleukin-1/genetics
dc.subject Interleukin-6/blood
dc.subject Polymorphism, Single Nucleotide
dc.subject Receptors, Interleukin-6/genetics
dc.subject Whites/genetics
dc.subject Genetics (clinical)
dc.subject Genetics
dc.subject Molecular Biology
dc.title Genome-wide association study of circulating interleukin 6 levels identifies novel loci
dc.type /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version Peer reviewed
dc.identifier.doi 10.1093/hmg/ddab023
dc.relation.url http://www.scopus.com/inward/record.url?scp=85106143662&partnerID=8YFLogxK
dc.contributor.department Faculty of Medicine


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