Genome-wide association study of circulating interleukin 6 levels identifies novel loci
Aslibekyan Stella; Trollor Julian; Slagboom Eline; Whincup Peter; Psaty Bruce M; Penninx Brenda; Sørensen Thorkild I A; Willemsen Gonneke; Jefferis Barbara; de Geus Eco; Hottenga Jouke-Jan; Dehghan Abbas; Delgado Graciela E; Marques-Vidal Pedro; Shah Tina; Jess Tine; Mellström Dan; Casas Juan P; Spector Tim; Jukema J Wouter; Humphries Steve E; Ohlsson Claes; Vollenweider Peter; Eriksson Johan G; Prins Bram P; Sattar Naveed; Thalamuthu Anbupalam; Rossing Peter; Deelen Joris; Morris Richard W; Räikkönen Katri; Evans David M; Sabater-Lleal Maria; Kumari Meena; Scharnagl Hubert; Koenig Wolfgang; Lu Chen; Hamsten Anders; Kleber Marcus E; Lahti Jari; van Dongen Jenny; Teumer Alexander; Sachdev Perminder S; Van Heemst Diana; Naderi Elnaz; Lehtimäki Terho; Rotter Jerome I; Gaunt Tom; Hingorani Aroon; Alizadeh Behrooz Z; CHARGE Inflammation Working Grp; Durda Peter; Standl Marie; Stacey David; Bis Joshua C; Homuth Georg; Bain Lisa; Armstrong Nicola J; Kutalik Zoltan; Nolte Ilja M; Hammarstedt Ann; Völker Uwe; Milaneschi Yuri; McLachlan Stela; Müller-Nurasyid Martina; Feitosa Mary F; Trompet Stella; Engmann Jorgen; Baumert Jens; Dedoussis George; Revez Joana A; Heinrich Joachim; Gudnason Vilmundur; März Winfried; Mather Karen A; Lawlor Deborah A; Porcu Eleonora; Kanoni Stavroula; Boomsma Dorret I; Ahluwalia Tarunveer S; Kajantie Eero; Kivimaki Mika; Ferreira Manuel A; Kemp John P; Ballantyne Christie M; Snieder Harold; Price Jackie F; Beekman Marian; Abdollahi Mohammadreza; Wannamethee S Goya; Mitchell Braxton D; Singhal Gaurav; Chang Yen-Pei C; Deary Ian J; Naitza Silvia; Harris Sarah E; Grallert Harald; Timpson Nicholas J; Jamshidi Yalda; Tanaka Toshiko; Thiering Elisabeth; Nauck Matthias; Petrelis Alexandros M; Eriksson Joel; Marioni Riccardo E; Jawahar Magdalene C; Boerwinkle Eric; Sennblad Bengt; St Pourcain Beate; Benjamin Emelia J; Seppälä Ilkka; Deloukas Panos; Rice Ken; Mooijaart Simon P; Stathopoulou Maria G; Silveira Angela; Ben-Shlomo Yoav; Jalkanen Sirpa; Visvikis-Siest Sophie; Toben Catherine; Marek Diana; Waldenberger Melanie; Arnett Donna K; Baune Bernhard T; Liu Yongmei; Raitakari Olli; Zabaneh Delilah
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
- Rinnakkaistallenteet [19207]