학술논문
Genome-wide association study of circulating interleukin 6 levels identifies novel loci
Document Type
Author
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; Seppala, 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; Harris, Sarah E.; Homuth, Georg; Hottenga, Jouke-Jan; Jalkanen, Sirpa; Jamshidi, Yalda; Jawahar, Magdalene C.; Jess, Tine; Kivimaki, Mika; Kleber, Marcus E.; Lahti, Jari; Liu, Yongmei; Marques-Vidal, Pedro; Mellstrom, Dan; Mooijaart, Simon P.; Muller-Nurasyid, Martina; Penninx, Brenda; Revez, Joana A.; Rossing, Peter; Raikkonen, Katri; Sattar, Naveed; Scharnagl, Hubert; Sennblad, Bengt; Silveira, Angela; St Pourcain, Beate; Timpson, Nicholas J.; Trollor, Julian; van Dongen, Jenny; Van Heemst, Diana; Visvikis-Siest, Sophie; Vollenweider, Peter; Volker, Uwe; Waldenberger, Melanie; Willemsen, Gonneke; Zabaneh, Delilah; Morris, Richard W.; Arnett, Donna K.; Baune, Bernhard T.; Boomsma, Dorret, I; Chang, Yen-Pei C.; Deary, Ian J.; Deloukas, Panos; Eriksson, Johan G.; Evans, David M.; Ferreira, Manuel A.; Gaunt, Tom; Gudnason, Vilmundur; Hamsten, Anders; Heinrich, Joachim; Hingorani, Aroon; Humphries, Steve E.; Jukema, J. Wouter; Koenig, Wolfgang; Kumari, Meena; Kutalik, Zoltan; Lawlor, Deborah A.; Lehtimaki, Terho; Marz, Winfried; Mather, Karen A.; Naitza, Silvia; Nauck, Matthias; Ohlsson, Claes; Price, Jackie F.; Raitakari, Olli; Rice, Ken; Sachdev, Perminder S.; Slagboom, Eline; Sorensen, Thorkild I. A.; Spector, Tim; Stacey, David; Stathopoulou, Maria G.; Tanaka, Toshiko; Wannamethee, S. Goya; Whincup, Peter; Rotter, Jerome, I; Dehghan, Abbas; Boerwinkle, Eric; Psaty, Bruce M.; Snieder, Harold; Alizadeh, Behrooz Z.
Source
Human Molecular Genetics. 30(5):393-409
Subject
Language
English
ISSN
0964-6906
1460-2083
1460-2083
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 67428 (n(discovery)=52654 and n(replication)=14774) 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, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.