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

Altres ajuts: Novo Nordisk Foundation (NNF18OC0052457). 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...

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Hauptverfasser:	Ahluwalia, Tarunveer Singh, Prins, Bram Peter, Abdollahi, Mohammadreza, Aslibekyan, Stella, Bain, Lisa J, Jefferis, Barbara, Baumert, Jens, Beekman, Marian, Ben-Shlomo, Yoav, Bis, Joshua C, Marek, Diana, Kajantie, Eero, Kanoni, Stavroula, Lu, Chen, Marioni, Riccardo E, McLachlan, Stela, Nolte, Ilja M, Petrelis, Alexandros M, Porcu, Eleonora, Seppälä, Ilkka, Shah, Tina, Singhal, Gaurav, Standl, Marie, Teumer, Alexander, Thalamuthu, Anbupalam, Thiering, Elisabeth, Trompet, Stella, Ballantyne, Christie M, Benjamin, Emelia J, Toben, Catherine, Dedoussis, George, Deelen, Joris, Engmann, Jorgen, Feitosa, Mary, Grallert, Harald, Hammarstedt, Ann, Harris, Sarah E, Hottenga, Jouke Jan, Jalkanen, Sirpa, Jawahar, Magdalene C, Jess, Tine, Kivimaki, Mika, Kleber, Marcus E, Lahti, Jari, Liu, Yongmei, Marques-Vidal, Pedro, Mellström, Dan, Mooijaart, Simon P, Penninx, Brenda WJH, Revez, Joana A, Rossing, Peter, Sattar, Naveed, Scharnagl, Hubert, Sennblad, Bengt, Silveira, Angela, Pourcain, Beate St, Trollor, Julian, Van Dongen, Jenny, Van Heemst, Diana, Visvikis-Siest, Sophie, Vollenweider, Peter, Waldenberger, Melanie, Willemsen, Gonneke, Zabaneh, Delilah, Morris, Richard W, Arnett, Donna K, Boomsma, Dorret I, Chang, Yen-Pei C, Deary, Ian J, Eriksson, Johan G, Evans, David M, Ferreira, Manuel A, Gaunt, Tom, Gudnason, Vilmundur, Hamsten, Anders, Heinrich, Joachim, Hingorani, Aroon, Humphries, Steve E, Koenig, Wolfgang, Kutalik, Zoltan, Lawlor, Deborah A, Lehtimäki, Terho, März, Winfried, Mather, Karen A, Nauck, Matthias, Ohlsson, Claes, Price, Jackie F, Raitakari, Olli, Rice, Ken, Sachdev, Perminder S, Sørensen, Thorkild I. A, Spector, Tim, Stacey, David, Stathopoulou, Maria G, Wannamethee, Sasiwarang Goya, Whincup, Peter, Dehghan, Abbas, Boerwinkle, Eric, Snieder, Harold, Alizadeh, Behrooz Ziad
Format:	Artikel
Sprache:	eng
Schlagworte:	Cohort Studies European Continental Ancestry Group Gene Expression Regulation Genetic Loci Genetic Predisposition to Disease Genome-Wide Association Study HLA-DRB1 Chains Humans Interleukin 1 Receptor Antagonist Protein Interleukin-1 Interleukin-6 Polymorphism, Single Nucleotide Receptors, Interleukin-6
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Zusammenfassung:	Altres ajuts: Novo Nordisk Foundation (NNF18OC0052457). 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.