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)
 
Avaa tiedosto
Lataukset: 



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


doi:10.1093/hmg/ddab023
Näytä kaikki kuvailutiedot
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202106296104

Kuvaus

Peer reviewed
Tiivistelmä
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.
Kokoelmat