Buchumschlag

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

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...

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Hauptverfasser: Ahluwalia, Tarun Veer Singh (VerfasserIn) , Prins, Bram P (VerfasserIn) , Abdollahi, Mohammadreza (VerfasserIn) , Armstrong, Nicola J (VerfasserIn) , Aslibekyan, Stella (VerfasserIn) , Bain, Lisa (VerfasserIn) , Jefferis, Barbara (VerfasserIn) , Baumert, Jens (VerfasserIn) , Beekman, Marian (VerfasserIn) , Ben-Shlomo, Yoav (VerfasserIn) , Bis, Joshua C (VerfasserIn) , Mitchell, Braxton D (VerfasserIn) , de Geus, Eco (VerfasserIn) , Delgado Gonzales de Kleber, Graciela (VerfasserIn) , Marek, Diana (VerfasserIn) , Eriksson, Joel (VerfasserIn) , Kajantie, Eero (VerfasserIn) , Kanoni, Stavroula (VerfasserIn) , Kemp, John P (VerfasserIn) , Lu, Chen (VerfasserIn) , Marioni, Riccardo E (VerfasserIn) , McLachlan, Stela (VerfasserIn) , Milaneschi, Yuri (VerfasserIn) , Nolte, Ilja M (VerfasserIn) , Petrelis, Alexandros M (VerfasserIn) , Porcu, Eleonora (VerfasserIn) , Sabater-Lleal, Maria (VerfasserIn) , Naderi, Elnaz (VerfasserIn) , Seppälä, Ilkka (VerfasserIn) , Shah, Tina (VerfasserIn) , Singhal, Gaurav (VerfasserIn) , Standl, Marie (VerfasserIn) , Teumer, Alexander (VerfasserIn) , Thalamuthu, Anbupalam (VerfasserIn) , Thiering, Elisabeth (VerfasserIn) , Trompet, Stella (VerfasserIn) , Ballantyne, Christie M (VerfasserIn) , Benjamin, Emelia J (VerfasserIn) , Casas, Juan P (VerfasserIn) , Toben, Catherine (VerfasserIn) , Dedoussis, George (VerfasserIn) , Deelen, Joris (VerfasserIn) , Durda, Peter (VerfasserIn) , Engmann, Jorgen (VerfasserIn) , Feitosa, Mary F (VerfasserIn) , Grallert, Harald (VerfasserIn) , Hammarstedt, Ann (VerfasserIn) , Harris, Sarah E (VerfasserIn) , Homuth, Georg (VerfasserIn) , Hottenga, Jouke-Jan (VerfasserIn) , Jalkanen, Sirpa (VerfasserIn) , Jamshidi, Yalda (VerfasserIn) , Jawahar, Magdalene C (VerfasserIn) , Jess, Tine (VerfasserIn) , Kivimaki, Mika (VerfasserIn) , Kleber, Marcus E. (VerfasserIn) , Lahti, Jari (VerfasserIn) , Liu, Yongmei (VerfasserIn) , Marques-Vidal, Pedro (VerfasserIn) , Mellström, Dan (VerfasserIn) , Mooijaart, Simon P (VerfasserIn) , Müller-Nurasyid, Martina (VerfasserIn) , Penninx, Brenda (VerfasserIn) , Revez, Joana A (VerfasserIn) , Rossing, Peter (VerfasserIn) , Räikkönen, Katri (VerfasserIn) , Sattar, Naveed (VerfasserIn) , Scharnagl, Hubert (VerfasserIn) , Sennblad, Bengt (VerfasserIn) , Silveira, Angela (VerfasserIn) , Pourcain, Beate St (VerfasserIn) , Timpson, Nicholas J (VerfasserIn) , Trollor, Julian (VerfasserIn) , van Dongen, Jenny (VerfasserIn) , Van Heemst, Diana (VerfasserIn) , Visvikis-Siest, Sophie (VerfasserIn) , Vollenweider, Peter (VerfasserIn) , Völker, Uwe (VerfasserIn) , Waldenberger, Melanie (VerfasserIn) , Willemsen, Gonneke (VerfasserIn) , Zabaneh, Delilah (VerfasserIn) , Morris, Richard W (VerfasserIn) , Arnett, Donna K (VerfasserIn) , Baune, Bernhard T (VerfasserIn) , Boomsma, Dorret I (VerfasserIn) , Chang, Yen-Pei C (VerfasserIn) , Deary, Ian J (VerfasserIn) , Deloukas, Panos (VerfasserIn) , Eriksson, Johan G (VerfasserIn) , Evans, David M (VerfasserIn) , Ferreira, Manuel A (VerfasserIn) , Gaunt, Tom (VerfasserIn) , Gudnason, Vilmundur (VerfasserIn) , Hamsten, Anders (VerfasserIn) , Heinrich, Joachim (VerfasserIn) , Hingorani, Aroon (VerfasserIn) , Humphries, Steve E (VerfasserIn) , Jukema, J Wouter (VerfasserIn) , Koenig, Wolfgang (VerfasserIn) , Kumari, Meena (VerfasserIn) , Kutalik, Zoltan (VerfasserIn) , Lawlor, Deborah A (VerfasserIn) , Lehtimäki, Terho (VerfasserIn) , März, Winfried (VerfasserIn) , Mather, Karen A (VerfasserIn) , Naitza, Silvia (VerfasserIn) , Nauck, Matthias (VerfasserIn) , Ohlsson, Claes (VerfasserIn) , Price, Jackie F (VerfasserIn) , Raitakari, Olli (VerfasserIn) , Rice, Ken (VerfasserIn) , Sachdev, Perminder S (VerfasserIn) , Slagboom, Eline (VerfasserIn) , Sørensen, Thorkild I A (VerfasserIn) , Spector, Tim (VerfasserIn) , Stacey, David (VerfasserIn) , Stathopoulou, Maria G (VerfasserIn) , Tanaka, Toshiko (VerfasserIn) , Wannamethee, S Goya (VerfasserIn) , Whincup, Peter (VerfasserIn) , Rotter, Jerome I (VerfasserIn) , Dehghan, Abbas (VerfasserIn) , Boerwinkle, Eric (VerfasserIn) , Psaty, Bruce M (VerfasserIn) , Snieder, Harold (VerfasserIn) , Alizadeh, Behrooz Z (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: March 2021
In: Human molecular genetics
Year: 2021, Jahrgang: 30, Heft: 5, Pages: 393-409
ISSN:1460-2083
DOI:10.1093/hmg/ddab023
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/hmg/ddab023
Volltext
Verfasserangaben:Tarunveer S. Ahluwalia, Bram P. Prins, Mohammadreza Abdollahi, Nicola J. Armstrong, Stella Aslibekyan, Lisa Bain, Barbara Jefferis, Jens Baumert, Marian Beekman, Yoav Ben-Shlomo, Joshua C. Bis, Braxton D. Mitchell, Eco de Geus, Graciela E. Delgado, Diana Marek, Joel Eriksson, Eero Kajantie, Stavroula Kanoni, John P. Kemp, Chen Lu, Riccardo E. Marioni, Stela McLachlan, Yuri Milaneschi, Ilja M. Nolte, Alexandros M. Petrelis, Eleonora Porcu, Maria Sabater-Lleal, Elnaz Naderi, Ilkka Seppälä, Tina Shah, Gaurav Singhal, Marie Standl, Alexander Teumer, Anbupalam Thalamuthu, Elisabeth Thiering, Stella Trompet, Christie M. Ballantyne, Emelia J. Benjamin, Juan P. Casas, Catherine Toben, George Dedoussis, Joris Deelen, Peter Durda, Jorgen Engmann, Mary F. Feitosa, Harald Grallert, Ann Hammarstedt, Sarah E. Harris, Georg Homuth, Jouke-Jan Hottenga, Sirpa Jalkanen, Yalda Jamshidi, Magdalene C. Jawahar, Tine Jess, Mika Kivimaki, Marcus E. Kleber, Jari Lahti, Yongmei Liu, Pedro Marques-Vidal, Dan Mellström, Simon P. Mooijaart, Martina Müller-Nurasyid, Brenda Penninx, Joana A. Revez, Peter Rossing, Katri Räikkönen, Naveed Sattar, Hubert Scharnagl, Bengt Sennblad, Angela Silveira, Beate St. Pourcain, Nicholas J. Timpson, Julian Trollor, Jenny van Dongen, Diana Van Heemst, Sophie Visvikis-Siest, Peter Vollenweider, Uwe Völker, Melanie Waldenberger, Gonneke Willemsen, Delilah Zabaneh, Richard W. Morris, Donna K. Arnett, Bernhard T. Baune, Dorret I. Boomsma, Yen-Pei C. Chang, Ian J. Deary, Panos Deloukas, Johan G. Eriksson, David M. Evans, Manuel A. Ferreira, Tom Gaunt, Vilmundur Gudnason, Anders Hamsten, Joachim Heinrich, Aroon Hingorani, Steve E. Humphries, J. Wouter Jukema, Wolfgang Koenig, Meena Kumari, Zoltan Kutalik, Deborah A. Lawlor, Terho Lehtimäki, Winfried März, Karen A. Mather, Silvia Naitza, Matthias Nauck, Claes Ohlsson, Jackie F. Price, Olli Raitakari, Ken Rice, Perminder S. Sachdev, Eline Slagboom, Thorkild I.A. Sørensen, Tim Spector, David Stacey, Maria G. Stathopoulou, Toshiko Tanaka, S. Goya Wannamethee, Peter Whincup, Jerome I. Rotter, Abbas Dehghan, Eric Boerwinkle, Bruce M. Psaty, Harold Snieder and Behrooz Z. Alizadeh

MARC

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245 1 0 |a Genome-wide association study of circulating interleukin 6 levels identifies novel loci  |c Tarunveer S. Ahluwalia, Bram P. Prins, Mohammadreza Abdollahi, Nicola J. Armstrong, Stella Aslibekyan, Lisa Bain, Barbara Jefferis, Jens Baumert, Marian Beekman, Yoav Ben-Shlomo, Joshua C. Bis, Braxton D. Mitchell, Eco de Geus, Graciela E. Delgado, Diana Marek, Joel Eriksson, Eero Kajantie, Stavroula Kanoni, John P. Kemp, Chen Lu, Riccardo E. Marioni, Stela McLachlan, Yuri Milaneschi, Ilja M. Nolte, Alexandros M. Petrelis, Eleonora Porcu, Maria Sabater-Lleal, Elnaz Naderi, Ilkka Seppälä, Tina Shah, Gaurav Singhal, Marie Standl, Alexander Teumer, Anbupalam Thalamuthu, Elisabeth Thiering, Stella Trompet, Christie M. Ballantyne, Emelia J. Benjamin, Juan P. Casas, Catherine Toben, George Dedoussis, Joris Deelen, Peter Durda, Jorgen Engmann, Mary F. Feitosa, Harald Grallert, Ann Hammarstedt, Sarah E. Harris, Georg Homuth, Jouke-Jan Hottenga, Sirpa Jalkanen, Yalda Jamshidi, Magdalene C. Jawahar, Tine Jess, Mika Kivimaki, Marcus E. Kleber, Jari Lahti, Yongmei Liu, Pedro Marques-Vidal, Dan Mellström, Simon P. Mooijaart, Martina Müller-Nurasyid, Brenda Penninx, Joana A. Revez, Peter Rossing, Katri Räikkönen, Naveed Sattar, Hubert Scharnagl, Bengt Sennblad, Angela Silveira, Beate St. Pourcain, Nicholas J. Timpson, Julian Trollor, Jenny van Dongen, Diana Van Heemst, Sophie Visvikis-Siest, Peter Vollenweider, Uwe Völker, Melanie Waldenberger, Gonneke Willemsen, Delilah Zabaneh, Richard W. Morris, Donna K. Arnett, Bernhard T. Baune, Dorret I. Boomsma, Yen-Pei C. Chang, Ian J. Deary, Panos Deloukas, Johan G. Eriksson, David M. Evans, Manuel A. Ferreira, Tom Gaunt, Vilmundur Gudnason, Anders Hamsten, Joachim Heinrich, Aroon Hingorani, Steve E. Humphries, J. Wouter Jukema, Wolfgang Koenig, Meena Kumari, Zoltan Kutalik, Deborah A. Lawlor, Terho Lehtimäki, Winfried März, Karen A. Mather, Silvia Naitza, Matthias Nauck, Claes Ohlsson, Jackie F. Price, Olli Raitakari, Ken Rice, Perminder S. Sachdev, Eline Slagboom, Thorkild I.A. Sørensen, Tim Spector, David Stacey, Maria G. Stathopoulou, Toshiko Tanaka, S. Goya Wannamethee, Peter Whincup, Jerome I. Rotter, Abbas Dehghan, Eric Boerwinkle, Bruce M. Psaty, Harold Snieder and Behrooz Z. Alizadeh 
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500 |a Gesehen am 15.09.2021 
520 |a 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 67 428 (ndiscovery = 52 654 and nreplication = 14 774) 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 = 1.8 × 10−11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10−10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10−122). 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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999 |a KXP-PPN1770718559  |e 3978318784 
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SER |a journal 
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SRT |a AHLUWALIATGENOMEWIDE2021 

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