%0 Journal Article %J Hum Mol Genet %D 2021 %T Genome-wide association study of circulating interleukin 6 levels identifies novel loci. %A Ahluwalia, Tarunveer S %A Prins, Bram P %A Abdollahi, Mohammadreza %A Armstrong, Nicola J %A Aslibekyan, Stella %A Bain, Lisa %A Jefferis, Barbara %A Baumert, Jens %A Beekman, Marian %A Ben-Shlomo, Yoav %A Bis, Joshua C %A Mitchell, Braxton D %A de Geus, Eco %A Delgado, Graciela E %A Marek, Diana %A Eriksson, Joel %A Kajantie, Eero %A Kanoni, Stavroula %A Kemp, John P %A Lu, Chen %A Marioni, Riccardo E %A McLachlan, Stela %A Milaneschi, Yuri %A Nolte, Ilja M %A Petrelis, Alexandros M %A Porcu, Eleonora %A Sabater-Lleal, Maria %A Naderi, Elnaz %A Seppälä, Ilkka %A Shah, Tina %A Singhal, Gaurav %A Standl, Marie %A Teumer, Alexander %A Thalamuthu, Anbupalam %A Thiering, Elisabeth %A Trompet, Stella %A Ballantyne, Christie M %A Benjamin, Emelia J %A Casas, Juan P %A Toben, Catherine %A Dedoussis, George %A Deelen, Joris %A Durda, Peter %A Engmann, Jorgen %A Feitosa, Mary F %A Grallert, Harald %A Hammarstedt, Ann %A Harris, Sarah E %A Homuth, Georg %A Hottenga, Jouke-Jan %A Jalkanen, Sirpa %A Jamshidi, Yalda %A Jawahar, Magdalene C %A Jess, Tine %A Kivimaki, Mika %A Kleber, Marcus E %A Lahti, Jari %A Liu, Yongmei %A Marques-Vidal, Pedro %A Mellström, Dan %A Mooijaart, Simon P %A Müller-Nurasyid, Martina %A Penninx, Brenda %A Revez, Joana A %A Rossing, Peter %A Räikkönen, Katri %A Sattar, Naveed %A Scharnagl, Hubert %A Sennblad, Bengt %A Silveira, Angela %A Pourcain, Beate St %A Timpson, Nicholas J %A Trollor, Julian %A van Dongen, Jenny %A van Heemst, Diana %A Visvikis-Siest, Sophie %A Vollenweider, Peter %A Völker, Uwe %A Waldenberger, Melanie %A Willemsen, Gonneke %A Zabaneh, Delilah %A Morris, Richard W %A Arnett, Donna K %A Baune, Bernhard T %A Boomsma, Dorret I %A Chang, Yen-Pei C %A Deary, Ian J %A Deloukas, Panos %A Eriksson, Johan G %A Evans, David M %A Ferreira, Manuel A %A Gaunt, Tom %A Gudnason, Vilmundur %A Hamsten, Anders %A Heinrich, Joachim %A Hingorani, Aroon %A Humphries, Steve E %A Jukema, J Wouter %A Koenig, Wolfgang %A Kumari, Meena %A Kutalik, Zoltán %A Lawlor, Deborah A %A Lehtimäki, Terho %A Marz, Winfried %A Mather, Karen A %A Naitza, Silvia %A Nauck, Matthias %A Ohlsson, Claes %A Price, Jackie F %A Raitakari, Olli %A Rice, Ken %A Sachdev, Perminder S %A Slagboom, Eline %A Sørensen, Thorkild I A %A Spector, Tim %A Stacey, David %A Stathopoulou, Maria G %A Tanaka, Toshiko %A Wannamethee, S Goya %A Whincup, Peter %A Rotter, Jerome I %A Dehghan, Abbas %A Eric Boerwinkle %A Psaty, Bruce M %A Snieder, Harold %A Alizadeh, Behrooz Z %K Cohort Studies %K Gene Expression Regulation %K Genetic Loci %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K HLA-DRB1 Chains %K Humans %K Interleukin 1 Receptor Antagonist Protein %K Interleukin-1 %K Interleukin-6 %K Polymorphism, Single Nucleotide %K Receptors, Interleukin-6 %K White People %X

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.

%B Hum Mol Genet %V 30 %P 393-409 %8 2021 Apr 27 %G eng %N 5 %1 https://www.ncbi.nlm.nih.gov/pubmed/33517400?dopt=Abstract %R 10.1093/hmg/ddab023