Genome-wide association study of circulating interleukin 6 levels identifies novel loci

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Ahluwalia , T S , Prins , B P , Abdollahi , M , Armstrong , N J , Aslibekyan , S , Bain , L , Jefferis , B , Baumert , J , Beekman , M , Ben-Shlomo , Y , Bis , J C , Mitchell , B D , de Geus , E , Delgado , G E , Marek , D , Eriksson , J , Kajantie , E , Kanoni , S , Kemp , J P , Lu , C , Marioni , R E , McLachlan , S , Milaneschi , Y , Nolte , I M , Petrelis , A M , Porcu , E , Sabater-Lleal , M , Naderi , E , Seppälä , I , Shah , T , Singhal , G , Standl , M , Teumer , A , Thalamuthu , A , Thiering , E , Trompet , S , Ballantyne , C M , Benjamin , E J , Casas , J P , Toben , C , Dedoussis , G , Deelen , J , Durda , P , Engmann , J , Feitosa , M F , Grallert , H , Hammarstedt , A , Harris , S E , Homuth , G , Hottenga , J-J , Jalkanen , S , Jamshidi , Y , Jawahar , M C , Jess , T , Kivimaki , M , Kleber , M E , Lahti , J , Liu , Y , Marques-Vidal , P , Mellström , D , Mooijaart , S P , Müller-Nurasyid , M , Penninx , B , Revez , J A , Rossing , P , Räikkönen , K , Sattar , N , Scharnagl , H , Sennblad , B , Silveira , A , Pourcain , B S , Timpson , N J , Trollor , J , Group , CHARGE I W , van Dongen , J , Van Heemst , D , Visvikis-Siest , S , Vollenweider , P , Völker , U , Waldenberger , M , Willemsen , G , Zabaneh , D , Morris , R W , Arnett , D K , Baune , B T , Boomsma , D I , Chang , Y-P C , Deary , I J , Deloukas , P , Eriksson , J G , Evans , D M , Ferreira , M A , Gaunt , T , Gudnason , V , Hamsten , A , Heinrich , J , Hingorani , A , Humphries , S E , Jukema , J W , Koenig , W , Kumari , M , Kutalik , Z , Lawlor , D A , Lehtimäki , T , März , W , Mather , K A , Naitza , S , Nauck , M , Ohlsson , C , Price , J F , Raitakari , O , Rice , K , Sachdev , P S , Slagboom , E , Sørensen , T I A , Spector , T , Stacey , D , Stathopoulou , M G , Tanaka , T , Wannamethee , S G , Whincup , P , Rotter , J I , Dehghan , A , Boerwinkle , E , Psaty , B M , Snieder , H & Alizadeh , B Z 2021 , ' Genome-wide association study of circulating interleukin 6 levels identifies novel loci ' , Human Molecular Genetics , vol. 30 , no. 5 , pp. 393-409 . https://doi.org/10.1093/hmg/ddab023

Title: Genome-wide association study of circulating interleukin 6 levels identifies novel loci
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; 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; Pourcain, Beate St; Timpson, Nicholas J; Trollor, Julian; Group, CHARGE Inflammation Working; 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
Contributor organization: HUS Children and Adolescents
Lastentautien yksikkö
Children's Hospital
Clinicum
Department of Bacteriology and Immunology
Department of Public Health
Department of Psychology and Logopedics
University of Helsinki
Research Programs Unit
Johan Eriksson / Principal Investigator
Department of General Practice and Primary Health Care
Doctoral Programme in Human Behaviour
Date: 2021-03-01
Language: eng
Number of pages: 17
Belongs to series: Human Molecular Genetics
ISSN: 0964-6906
DOI: https://doi.org/10.1093/hmg/ddab023
URI: http://hdl.handle.net/10138/332456
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.
Subject: 3111 Biomedicine
1184 Genetics, developmental biology, physiology
1182 Biochemistry, cell and molecular biology
C-REACTIVE PROTEIN
SYSTEMIC-LUPUS-ERYTHEMATOSUS
RECEPTOR IL-6R GENE
SUSCEPTIBILITY LOCI
RHEUMATOID-ARTHRITIS
CHRONIC INFLAMMATION
PRODUCE IL-6
DISEASE
CELLS
ARCHITECTURE
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: acceptedVersion


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