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

Ahluwalia, Tarunveer S and Prins, Bram P and Abdollahi, Mohammadreza and Armstrong, Nicola J and Aslibekyan, Stella and Bain, Lisa and Jefferis, Barbara and Baumert, Jens and Beekman, Marian and Ben-Shlomo, Yoav and Bis, Joshua C and Mitchell, Braxton D and de Geus, Eco and Delgado, Graciela E and Marek, Diana and Eriksson, Joel and Kajantie, Eero and Kanoni, Stavroula and Kemp, John P and Lu, Chen and Marioni, Riccardo E and McLachlan, Stela and Milaneschi, Yuri and Nolte, Ilja M and Petrelis, Alexandros M and Porcu, Eleonora and Sabater-Lleal, Maria and Naderi, Elnaz and Seppälä, Ilkka and Shah, Tina and Singhal, Gaurav and Standl, Marie and Teumer, Alexander and Thalamuthu, Anbupalam and Thiering, Elisabeth and Trompet, Stella and Ballantyne, Christie M and Benjamin, Emelia J and Casas, Juan P and Toben, Catherine and Dedoussis, George and Deelen, Joris and Durda, Peter and Engmann, Jorgen and Feitosa, Mary F and Grallert, Harald and Hammarstedt, Ann and Harris, Sarah E and Homuth, Georg and Hottenga, Jouke-Jan and Jalkanen, Sirpa and Jamshidi, Yalda and Jawahar, Magdalene C and Jess, Tine and Kivimaki, Mika and Kleber, Marcus E and Lahti, Jari and Liu, Yongmei and Marques-Vidal, Pedro and Mellström, Dan and Mooijaart, Simon P and Müller-Nurasyid, Martina and Penninx, Brenda and Revez, Joana A and Rossing, Peter and Räikkönen, Katri and Sattar, Naveed and Scharnagl, Hubert and Sennblad, Bengt and Silveira, Angela and Pourcain, Beate St and Timpson, Nicholas J and Trollor, Julian and CHARGE Inflammation Working Group, and van Dongen, Jenny and Van Heemst, Diana and Visvikis-Siest, Sophie and Vollenweider, Peter and Völker, Uwe and Waldenberger, Melanie and Willemsen, Gonneke and Zabaneh, Delilah and Morris, Richard W and Arnett, Donna K and Baune, Bernhard T and Boomsma, Dorret I and Chang, Yen-Pei C and Deary, Ian J and Deloukas, Panos and Eriksson, Johan G and Evans, David M and Ferreira, Manuel A and Gaunt, Tom and Gudnason, Vilmundur and Hamsten, Anders and Heinrich, Joachim and Hingorani, Aroon and Humphries, Steve E and Jukema, J Wouter and Koenig, Wolfgang and Kumari, Meena and Kutalik, Zoltan and Lawlor, Deborah A and Lehtimäki, Terho and März, Winfried and Mather, Karen A and Naitza, Silvia and Nauck, Matthias and Ohlsson, Claes and Price, Jackie F and Raitakari, Olli and Rice, Ken and Sachdev, Perminder S and Slagboom, Eline and Sørensen, Thorkild IA and Spector, Tim and Stacey, David and Stathopoulou, Maria G and Tanaka, Toshiko and Wannamethee, S Goya and Whincup, Peter and Rotter, Jerome I and Dehghan, Abbas and Boerwinkle, Eric and Psaty, Bruce M and Snieder, Harold and Alizadeh, Behrooz Z (2021) 'Genome-wide association study of circulating interleukin 6 levels identifies novel loci.' Human Molecular Genetics, 30 (5). 393 - 409. ISSN 0964-6906

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: CHARGE Inflammation Working Group
Divisions: Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Elements
Date Deposited: 14 Oct 2021 09:19
Last Modified: 14 Oct 2021 09:19
URI: http://repository.essex.ac.uk/id/eprint/31020

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