A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Genome-wide association study of circulating interleukin 6 levels identifies novel loci
Tekijät: 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
Kustantaja: OXFORD UNIV PRESS
Julkaisuvuosi: 2021
Journal: Human Molecular Genetics
Tietokannassa oleva lehden nimi: HUMAN MOLECULAR GENETICS
Lehden akronyymi: HUM MOL GENET
Vuosikerta: 30
Numero: 5
Aloitussivu: 393
Lopetussivu: 409
Sivujen määrä: 17
ISSN: 0964-6906
eISSN: 1460-2083
DOI: https://doi.org/10.1093/hmg/ddab023
Verkko-osoite: https://academic.oup.com/hmg/article/30/5/393/6124523
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/58624803
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.
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