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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...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Oxford University Press
2021
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098112/ https://www.ncbi.nlm.nih.gov/pubmed/33517400 http://dx.doi.org/10.1093/hmg/ddab023 |
| _version_ | 1783688439215947776 |
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| 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 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 |
| author_facet | 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 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 |
| author_sort | Ahluwalia, Tarunveer S |
| collection | PubMed |
| description | 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 (n(discovery) = 52 654 and n(replication) = 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, (P(combined) = 1.8 × 10(−11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P(combined) = 1.5 × 10(−10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P(combined) = 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. |
| format | Online Article Text |
| id | pubmed-8098112 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Oxford University Press |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-80981122021-05-10 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 Pourcain, Beate St 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 Hum Mol Genet Association Studies Article 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 (n(discovery) = 52 654 and n(replication) = 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, (P(combined) = 1.8 × 10(−11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P(combined) = 1.5 × 10(−10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P(combined) = 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. Oxford University Press 2021-01-30 /pmc/articles/PMC8098112/ /pubmed/33517400 http://dx.doi.org/10.1093/hmg/ddab023 Text en © The Author(s) 2021. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| spellingShingle | Association Studies Article 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 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 Genome-wide association study of circulating interleukin 6 levels identifies novel loci |
| title | Genome-wide association study of circulating interleukin 6 levels identifies novel loci |
| title_full | Genome-wide association study of circulating interleukin 6 levels identifies novel loci |
| title_fullStr | Genome-wide association study of circulating interleukin 6 levels identifies novel loci |
| title_full_unstemmed | Genome-wide association study of circulating interleukin 6 levels identifies novel loci |
| title_short | Genome-wide association study of circulating interleukin 6 levels identifies novel loci |
| title_sort | genome-wide association study of circulating interleukin 6 levels identifies novel loci |
| topic | Association Studies Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098112/ https://www.ncbi.nlm.nih.gov/pubmed/33517400 http://dx.doi.org/10.1093/hmg/ddab023 |
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