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Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and...
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2023
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185546/ https://www.ncbi.nlm.nih.gov/pubmed/37188663 http://dx.doi.org/10.1038/s41467-023-36120-z |
| _version_ | 1785042379117428736 |
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| author | Ollila, Hanna M. Sharon, Eilon Lin, Ling Sinnott-Armstrong, Nasa Ambati, Aditya Yogeshwar, Selina M. Hillary, Ryan P. Jolanki, Otto Faraco, Juliette Einen, Mali Luo, Guo Zhang, Jing Han, Fang Yan, Han Dong, Xiao Song Li, Jing Zhang, Jun Hong, Seung-Chul Kim, Tae Won Dauvilliers, Yves Barateau, Lucie Lammers, Gert Jan Fronczek, Rolf Mayer, Geert Santamaria, Joan Arnulf, Isabelle Knudsen-Heier, Stine Bredahl, May Kristin Lyamouri Thorsby, Per Medbøe Plazzi, Giuseppe Pizza, Fabio Moresco, Monica Crowe, Catherine Van den Eeden, Stephen K. Lecendreux, Michel Bourgin, Patrice Kanbayashi, Takashi Martínez-Orozco, Francisco J. Peraita-Adrados, Rosa Benetó, Antonio Montplaisir, Jacques Desautels, Alex Huang, Yu-Shu Jennum, Poul Nevsimalova, Sona Kemlink, David Iranzo, Alex Overeem, Sebastiaan Wierzbicka, Aleksandra Geisler, Peter Sonka, Karel Honda, Makoto Högl, Birgit Stefani, Ambra Coelho, Fernando Morgadinho Mantovani, Vilma Feketeova, Eva Wadelius, Mia Eriksson, Niclas Smedje, Hans Hallberg, Pär Hesla, Per Egil Rye, David Pelin, Zerrin Ferini-Strambi, Luigi Bassetti, Claudio L. Mathis, Johannes Khatami, Ramin Aran, Adi Nampoothiri, Sheela Olsson, Tomas Kockum, Ingrid Partinen, Markku Perola, Markus Kornum, Birgitte R. Rueger, Sina Winkelmann, Juliane Miyagawa, Taku Toyoda, Hiromi Khor, Seik-Soon Shimada, Mihoko Tokunaga, Katsushi Rivas, Manuel Pritchard, Jonathan K. Risch, Neil Kutalik, Zoltan O’Hara, Ruth Hallmayer, Joachim Ye, Chun Jimmie Mignot, Emmanuel J. |
| author_facet | Ollila, Hanna M. Sharon, Eilon Lin, Ling Sinnott-Armstrong, Nasa Ambati, Aditya Yogeshwar, Selina M. Hillary, Ryan P. Jolanki, Otto Faraco, Juliette Einen, Mali Luo, Guo Zhang, Jing Han, Fang Yan, Han Dong, Xiao Song Li, Jing Zhang, Jun Hong, Seung-Chul Kim, Tae Won Dauvilliers, Yves Barateau, Lucie Lammers, Gert Jan Fronczek, Rolf Mayer, Geert Santamaria, Joan Arnulf, Isabelle Knudsen-Heier, Stine Bredahl, May Kristin Lyamouri Thorsby, Per Medbøe Plazzi, Giuseppe Pizza, Fabio Moresco, Monica Crowe, Catherine Van den Eeden, Stephen K. Lecendreux, Michel Bourgin, Patrice Kanbayashi, Takashi Martínez-Orozco, Francisco J. Peraita-Adrados, Rosa Benetó, Antonio Montplaisir, Jacques Desautels, Alex Huang, Yu-Shu Jennum, Poul Nevsimalova, Sona Kemlink, David Iranzo, Alex Overeem, Sebastiaan Wierzbicka, Aleksandra Geisler, Peter Sonka, Karel Honda, Makoto Högl, Birgit Stefani, Ambra Coelho, Fernando Morgadinho Mantovani, Vilma Feketeova, Eva Wadelius, Mia Eriksson, Niclas Smedje, Hans Hallberg, Pär Hesla, Per Egil Rye, David Pelin, Zerrin Ferini-Strambi, Luigi Bassetti, Claudio L. Mathis, Johannes Khatami, Ramin Aran, Adi Nampoothiri, Sheela Olsson, Tomas Kockum, Ingrid Partinen, Markku Perola, Markus Kornum, Birgitte R. Rueger, Sina Winkelmann, Juliane Miyagawa, Taku Toyoda, Hiromi Khor, Seik-Soon Shimada, Mihoko Tokunaga, Katsushi Rivas, Manuel Pritchard, Jonathan K. Risch, Neil Kutalik, Zoltan O’Hara, Ruth Hallmayer, Joachim Ye, Chun Jimmie Mignot, Emmanuel J. |
| author_sort | Ollila, Hanna M. |
| collection | PubMed |
| description | Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®. |
| format | Online Article Text |
| id | pubmed-10185546 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2023 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-101855462023-05-17 Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy Ollila, Hanna M. Sharon, Eilon Lin, Ling Sinnott-Armstrong, Nasa Ambati, Aditya Yogeshwar, Selina M. Hillary, Ryan P. Jolanki, Otto Faraco, Juliette Einen, Mali Luo, Guo Zhang, Jing Han, Fang Yan, Han Dong, Xiao Song Li, Jing Zhang, Jun Hong, Seung-Chul Kim, Tae Won Dauvilliers, Yves Barateau, Lucie Lammers, Gert Jan Fronczek, Rolf Mayer, Geert Santamaria, Joan Arnulf, Isabelle Knudsen-Heier, Stine Bredahl, May Kristin Lyamouri Thorsby, Per Medbøe Plazzi, Giuseppe Pizza, Fabio Moresco, Monica Crowe, Catherine Van den Eeden, Stephen K. Lecendreux, Michel Bourgin, Patrice Kanbayashi, Takashi Martínez-Orozco, Francisco J. Peraita-Adrados, Rosa Benetó, Antonio Montplaisir, Jacques Desautels, Alex Huang, Yu-Shu Jennum, Poul Nevsimalova, Sona Kemlink, David Iranzo, Alex Overeem, Sebastiaan Wierzbicka, Aleksandra Geisler, Peter Sonka, Karel Honda, Makoto Högl, Birgit Stefani, Ambra Coelho, Fernando Morgadinho Mantovani, Vilma Feketeova, Eva Wadelius, Mia Eriksson, Niclas Smedje, Hans Hallberg, Pär Hesla, Per Egil Rye, David Pelin, Zerrin Ferini-Strambi, Luigi Bassetti, Claudio L. Mathis, Johannes Khatami, Ramin Aran, Adi Nampoothiri, Sheela Olsson, Tomas Kockum, Ingrid Partinen, Markku Perola, Markus Kornum, Birgitte R. Rueger, Sina Winkelmann, Juliane Miyagawa, Taku Toyoda, Hiromi Khor, Seik-Soon Shimada, Mihoko Tokunaga, Katsushi Rivas, Manuel Pritchard, Jonathan K. Risch, Neil Kutalik, Zoltan O’Hara, Ruth Hallmayer, Joachim Ye, Chun Jimmie Mignot, Emmanuel J. Nat Commun Article Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®. Nature Publishing Group UK 2023-05-15 /pmc/articles/PMC10185546/ /pubmed/37188663 http://dx.doi.org/10.1038/s41467-023-36120-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Ollila, Hanna M. Sharon, Eilon Lin, Ling Sinnott-Armstrong, Nasa Ambati, Aditya Yogeshwar, Selina M. Hillary, Ryan P. Jolanki, Otto Faraco, Juliette Einen, Mali Luo, Guo Zhang, Jing Han, Fang Yan, Han Dong, Xiao Song Li, Jing Zhang, Jun Hong, Seung-Chul Kim, Tae Won Dauvilliers, Yves Barateau, Lucie Lammers, Gert Jan Fronczek, Rolf Mayer, Geert Santamaria, Joan Arnulf, Isabelle Knudsen-Heier, Stine Bredahl, May Kristin Lyamouri Thorsby, Per Medbøe Plazzi, Giuseppe Pizza, Fabio Moresco, Monica Crowe, Catherine Van den Eeden, Stephen K. Lecendreux, Michel Bourgin, Patrice Kanbayashi, Takashi Martínez-Orozco, Francisco J. Peraita-Adrados, Rosa Benetó, Antonio Montplaisir, Jacques Desautels, Alex Huang, Yu-Shu Jennum, Poul Nevsimalova, Sona Kemlink, David Iranzo, Alex Overeem, Sebastiaan Wierzbicka, Aleksandra Geisler, Peter Sonka, Karel Honda, Makoto Högl, Birgit Stefani, Ambra Coelho, Fernando Morgadinho Mantovani, Vilma Feketeova, Eva Wadelius, Mia Eriksson, Niclas Smedje, Hans Hallberg, Pär Hesla, Per Egil Rye, David Pelin, Zerrin Ferini-Strambi, Luigi Bassetti, Claudio L. Mathis, Johannes Khatami, Ramin Aran, Adi Nampoothiri, Sheela Olsson, Tomas Kockum, Ingrid Partinen, Markku Perola, Markus Kornum, Birgitte R. Rueger, Sina Winkelmann, Juliane Miyagawa, Taku Toyoda, Hiromi Khor, Seik-Soon Shimada, Mihoko Tokunaga, Katsushi Rivas, Manuel Pritchard, Jonathan K. Risch, Neil Kutalik, Zoltan O’Hara, Ruth Hallmayer, Joachim Ye, Chun Jimmie Mignot, Emmanuel J. Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy |
| title | Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy |
| title_full | Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy |
| title_fullStr | Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy |
| title_full_unstemmed | Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy |
| title_short | Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy |
| title_sort | narcolepsy risk loci outline role of t cell autoimmunity and infectious triggers in narcolepsy |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185546/ https://www.ncbi.nlm.nih.gov/pubmed/37188663 http://dx.doi.org/10.1038/s41467-023-36120-z |
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