Genome-wide association study of circulating interleukin 6 levels identifies novel loci
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; Seppälä 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; Mellström Dan; Mooijaart Simon P; Müller-Nurasyid Martina; Penninx Brenda; Revez Joana A; Rossing Peter; Räikkönen 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; Völker 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; Lehtimäki Terho; März Winfried; Mather Karen A; Naitza Silvia; Nauck Matthias; Ohlsson Claes; Price Jackie F; Raitakari Olli; Rice Ken; Sachdev Perminder S; Slagboom Eline; Sørensen 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; CHARGE Inflammation Working Grp
https://urn.fi/URN:NBN:fi-fe2021093047994
Tiivistelmä
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 (ndiscovery=52654 and nreplication=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, (Pcombined=1.8x10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined=1.5x10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined=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.
Kokoelmat
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