| Literature DB >> 33517400 |
Tarunveer S Ahluwalia1,2, Bram P Prins3, Mohammadreza Abdollahi3, Nicola J Armstrong4, Stella Aslibekyan5, Lisa Bain6, Barbara Jefferis7, Jens Baumert8, Marian Beekman9, Yoav Ben-Shlomo10, Joshua C Bis11, Braxton D Mitchell12, Eco de Geus13,14, Graciela E Delgado15, Diana Marek16, Joel Eriksson17, Eero Kajantie18,19, Stavroula Kanoni20, John P Kemp21,22, Chen Lu23, Riccardo E Marioni24,25, Stela McLachlan26, Yuri Milaneschi27, Ilja M Nolte3, Alexandros M Petrelis28, Eleonora Porcu29, Maria Sabater-Lleal30,31, Elnaz Naderi3, Ilkka Seppälä32, Tina Shah33, Gaurav Singhal34, Marie Standl8, Alexander Teumer35, Anbupalam Thalamuthu36, Elisabeth Thiering8,37, Stella Trompet38,39, Christie M Ballantyne40, Emelia J Benjamin41,42, Juan P Casas43, Catherine Toben34, George Dedoussis44, Joris Deelen9,45, Peter Durda46, Jorgen Engmann33, Mary F Feitosa47, Harald Grallert8,48, Ann Hammarstedt49, Sarah E Harris25,50, Georg Homuth51, Jouke-Jan Hottenga13,14, Sirpa Jalkanen52,53, Yalda Jamshidi54, Magdalene C Jawahar34, Tine Jess55, Mika Kivimaki56, Marcus E Kleber15, Jari Lahti57,58, Yongmei Liu59, Pedro Marques-Vidal60,61, Dan Mellström17, Simon P Mooijaart39, Martina Müller-Nurasyid62,63, Brenda Penninx27, Joana A Revez6, Peter Rossing1,64, Katri Räikkönen58, Naveed Sattar65, Hubert Scharnagl66, Bengt Sennblad30,67, Angela Silveira30, Beate St Pourcain22,68,69, Nicholas J Timpson22, Julian Trollor36,70, Jenny van Dongen13,14, Diana Van Heemst40, Sophie Visvikis-Siest28, Peter Vollenweider60,61, Uwe Völker52, Melanie Waldenberger8, Gonneke Willemsen13,14, Delilah Zabaneh71, Richard W Morris72, Donna K Arnett73, Bernhard T Baune74,75,76, Dorret I Boomsma13,14, Yen-Pei C Chang12, Ian J Deary25,50, Panos Deloukas20,77, Johan G Eriksson78,79, David M Evans21,22, Manuel A Ferreira6, Tom Gaunt80,81, Vilmundur Gudnason82,83, Anders Hamsten30, Joachim Heinrich8,84,85, Aroon Hingorani33, Steve E Humphries33, J Wouter Jukema39,86, Wolfgang Koenig87,88,89, Meena Kumari56,90, Zoltan Kutalik16,91, Deborah A Lawlor80,81, Terho Lehtimäki32, Winfried März15,66,92, Karen A Mather36,93, Silvia Naitza29, Matthias Nauck94,95, Claes Ohlsson17, Jackie F Price26, Olli Raitakari96,97,98, Ken Rice99, Perminder S Sachdev36,100, Eline Slagboom9,45, Thorkild I A Sørensen101,102, Tim Spector103, David Stacey104, Maria G Stathopoulou28, Toshiko Tanaka105, S Goya Wannamethee7, Peter Whincup106, Jerome I Rotter107, Abbas Dehghan108, Eric Boerwinkle109,110, Bruce M Psaty11,111, Harold Snieder3, Behrooz Z Alizadeh3.
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.Entities:
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Year: 2021 PMID： 33517400 PMCID： PMC8098112 DOI： 10.1093/hmg/ddab023
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150