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

CHARGE Inflammation Working Group; Ahluwalia,Tarunveer S.; Prins,Bram P.; Abdollahi,Mohammadreza; Armstrong,Nicola J.; Aslibekyan,Stella; Bain,Lisa; Jefferis,Barbara; Baumert,Jens; Beekman,Marian; Ben-Shlomo,Yoav; Bis,Joshua C.; Mitchell,Braxton D.; de Geus,Eco; Delgado,Graciela E.; Marek,Diana; Eriksson,Joel; Kajantie,Eero; Kanoni,Stavroula; Kemp,John P.; Lu,Chen; Marioni,Riccardo E.; McLachlan,Stela; Milaneschi,Yuri; Nolte,Ilja M.; Petrelis,Alexandros M.; Porcu,Eleonora; Sabater-Lleal,Maria; Naderi,Elnaz; Seppälä,Ilkka; Shah,Tina; Singhal,Gaurav; Standl,Marie; Teumer,Alexander; Thalamuthu,Anbupalam; Thiering,Elisabeth; Trompet,Stella; Ballantyne,Christie M.; Benjamin,Emelia J.; Casas,Juan P.; Toben,Catherine; Dedoussis,George; Deelen,Joris; Durda,Peter; Engmann,Jorgen; Feitosa,Mary F.; Grallert,Harald; Hammarstedt,Ann; Lahti,Jari; Eriksson,Johan G.; Lehtimäki,Terho (2021)
 
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CHARGE Inflammation Working Group
Ahluwalia,Tarunveer S.
Prins,Bram P.
Abdollahi,Mohammadreza
Armstrong,Nicola J.
Aslibekyan,Stella
Bain,Lisa
Jefferis,Barbara
Baumert,Jens
Beekman,Marian
Ben-Shlomo,Yoav
Bis,Joshua C.
Mitchell,Braxton D.
de Geus,Eco
Delgado,Graciela E.
Marek,Diana
Eriksson,Joel
Kajantie,Eero
Kanoni,Stavroula
Kemp,John P.
Lu,Chen
Marioni,Riccardo E.
McLachlan,Stela
Milaneschi,Yuri
Nolte,Ilja M.
Petrelis,Alexandros M.
Porcu,Eleonora
Sabater-Lleal,Maria
Naderi,Elnaz
Seppälä,Ilkka
Shah,Tina
Singhal,Gaurav
Standl,Marie
Teumer,Alexander
Thalamuthu,Anbupalam
Thiering,Elisabeth
Trompet,Stella
Ballantyne,Christie M.
Benjamin,Emelia J.
Casas,Juan P.
Toben,Catherine
Dedoussis,George
Deelen,Joris
Durda,Peter
Engmann,Jorgen
Feitosa,Mary F.
Grallert,Harald
Hammarstedt,Ann
Lahti,Jari
Eriksson,Johan G.
Lehtimäki,Terho
2021


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doi:10.1093/hmg/ddab023
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http://urn.fi/URN:NBN:fi:tuni-202106296104

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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.
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