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European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation
Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohort...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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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/PMC10550990/ https://www.ncbi.nlm.nih.gov/pubmed/37794016 http://dx.doi.org/10.1038/s41467-023-41180-2 |
| _version_ | 1785115668295712768 |
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| author | Budu-Aggrey, Ashley Kilanowski, Anna Sobczyk, Maria K. Shringarpure, Suyash S. Mitchell, Ruth Reis, Kadri Reigo, Anu Mägi, Reedik Nelis, Mari Tanaka, Nao Brumpton, Ben M. Thomas, Laurent F. Sole-Navais, Pol Flatley, Christopher Espuela-Ortiz, Antonio Herrera-Luis, Esther Lominchar, Jesus V. T. Bork-Jensen, Jette Marenholz, Ingo Arnau-Soler, Aleix Jeong, Ayoung Fawcett, Katherine A. Baurecht, Hansjorg Rodriguez, Elke Alves, Alexessander Couto Kumar, Ashish Sleiman, Patrick M. Chang, Xiao Medina-Gomez, Carolina Hu, Chen Xu, Cheng-jian Qi, Cancan El-Heis, Sarah Titcombe, Philip Antoun, Elie Fadista, João Wang, Carol A. Thiering, Elisabeth Wu, Baojun Kress, Sara Kothalawala, Dilini M. Kadalayil, Latha Duan, Jiasong Zhang, Hongmei Hadebe, Sabelo Hoffmann, Thomas Jorgenson, Eric Choquet, Hélène Risch, Neil Njølstad, Pål Andreassen, Ole A. Johansson, Stefan Almqvist, Catarina Gong, Tong Ullemar, Vilhelmina Karlsson, Robert Magnusson, Patrik K. E. Szwajda, Agnieszka Burchard, Esteban G. Thyssen, Jacob P. Hansen, Torben Kårhus, Line L. Dantoft, Thomas M. Jeanrenaud, Alexander C.S.N. Ghauri, Ahla Arnold, Andreas Homuth, Georg Lau, Susanne Nöthen, Markus M. Hübner, Norbert Imboden, Medea Visconti, Alessia Falchi, Mario Bataille, Veronique Hysi, Pirro Ballardini, Natalia Boomsma, Dorret I. Hottenga, Jouke J. Müller-Nurasyid, Martina Ahluwalia, Tarunveer S. Stokholm, Jakob Chawes, Bo Schoos, Ann-Marie M. Esplugues, Ana Bustamante, Mariona Raby, Benjamin Arshad, Syed German, Chris Esko, Tõnu Milani, Lili A. Metspalu, Andres Terao, Chikashi Abuabara, Katrina Løset, Mari Hveem, Kristian Jacobsson, Bo Pino-Yanes, Maria Strachan, David P. Grarup, Niels Linneberg, Allan Lee, Young-Ae Probst-Hensch, Nicole Weidinger, Stephan Jarvelin, Marjo-Riitta Melén, Erik Hakonarson, Hakon Irvine, Alan D. Jarvis, Deborah Nijsten, Tamar Duijts, Liesbeth Vonk, Judith M. Koppelmann, Gerard H. Godfrey, Keith M. Barton, Sheila J. Feenstra, Bjarke Pennell, Craig E. Sly, Peter D. Holt, Patrick G. Williams, L. Keoki Bisgaard, Hans Bønnelykke, Klaus Curtin, John Simpson, Angela Murray, Clare Schikowski, Tamara Bunyavanich, Supinda Weiss, Scott T. Holloway, John W. Min, Josine L. Brown, Sara J. Standl, Marie Paternoster, Lavinia |
| author_facet | Budu-Aggrey, Ashley Kilanowski, Anna Sobczyk, Maria K. Shringarpure, Suyash S. Mitchell, Ruth Reis, Kadri Reigo, Anu Mägi, Reedik Nelis, Mari Tanaka, Nao Brumpton, Ben M. Thomas, Laurent F. Sole-Navais, Pol Flatley, Christopher Espuela-Ortiz, Antonio Herrera-Luis, Esther Lominchar, Jesus V. T. Bork-Jensen, Jette Marenholz, Ingo Arnau-Soler, Aleix Jeong, Ayoung Fawcett, Katherine A. Baurecht, Hansjorg Rodriguez, Elke Alves, Alexessander Couto Kumar, Ashish Sleiman, Patrick M. Chang, Xiao Medina-Gomez, Carolina Hu, Chen Xu, Cheng-jian Qi, Cancan El-Heis, Sarah Titcombe, Philip Antoun, Elie Fadista, João Wang, Carol A. Thiering, Elisabeth Wu, Baojun Kress, Sara Kothalawala, Dilini M. Kadalayil, Latha Duan, Jiasong Zhang, Hongmei Hadebe, Sabelo Hoffmann, Thomas Jorgenson, Eric Choquet, Hélène Risch, Neil Njølstad, Pål Andreassen, Ole A. Johansson, Stefan Almqvist, Catarina Gong, Tong Ullemar, Vilhelmina Karlsson, Robert Magnusson, Patrik K. E. Szwajda, Agnieszka Burchard, Esteban G. Thyssen, Jacob P. Hansen, Torben Kårhus, Line L. Dantoft, Thomas M. Jeanrenaud, Alexander C.S.N. Ghauri, Ahla Arnold, Andreas Homuth, Georg Lau, Susanne Nöthen, Markus M. Hübner, Norbert Imboden, Medea Visconti, Alessia Falchi, Mario Bataille, Veronique Hysi, Pirro Ballardini, Natalia Boomsma, Dorret I. Hottenga, Jouke J. Müller-Nurasyid, Martina Ahluwalia, Tarunveer S. Stokholm, Jakob Chawes, Bo Schoos, Ann-Marie M. Esplugues, Ana Bustamante, Mariona Raby, Benjamin Arshad, Syed German, Chris Esko, Tõnu Milani, Lili A. Metspalu, Andres Terao, Chikashi Abuabara, Katrina Løset, Mari Hveem, Kristian Jacobsson, Bo Pino-Yanes, Maria Strachan, David P. Grarup, Niels Linneberg, Allan Lee, Young-Ae Probst-Hensch, Nicole Weidinger, Stephan Jarvelin, Marjo-Riitta Melén, Erik Hakonarson, Hakon Irvine, Alan D. Jarvis, Deborah Nijsten, Tamar Duijts, Liesbeth Vonk, Judith M. Koppelmann, Gerard H. Godfrey, Keith M. Barton, Sheila J. Feenstra, Bjarke Pennell, Craig E. Sly, Peter D. Holt, Patrick G. Williams, L. Keoki Bisgaard, Hans Bønnelykke, Klaus Curtin, John Simpson, Angela Murray, Clare Schikowski, Tamara Bunyavanich, Supinda Weiss, Scott T. Holloway, John W. Min, Josine L. Brown, Sara J. Standl, Marie Paternoster, Lavinia |
| author_sort | Budu-Aggrey, Ashley |
| collection | PubMed |
| description | Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities. |
| format | Online Article Text |
| id | pubmed-10550990 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2023 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-105509902023-10-06 European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation Budu-Aggrey, Ashley Kilanowski, Anna Sobczyk, Maria K. Shringarpure, Suyash S. Mitchell, Ruth Reis, Kadri Reigo, Anu Mägi, Reedik Nelis, Mari Tanaka, Nao Brumpton, Ben M. Thomas, Laurent F. Sole-Navais, Pol Flatley, Christopher Espuela-Ortiz, Antonio Herrera-Luis, Esther Lominchar, Jesus V. T. Bork-Jensen, Jette Marenholz, Ingo Arnau-Soler, Aleix Jeong, Ayoung Fawcett, Katherine A. Baurecht, Hansjorg Rodriguez, Elke Alves, Alexessander Couto Kumar, Ashish Sleiman, Patrick M. Chang, Xiao Medina-Gomez, Carolina Hu, Chen Xu, Cheng-jian Qi, Cancan El-Heis, Sarah Titcombe, Philip Antoun, Elie Fadista, João Wang, Carol A. Thiering, Elisabeth Wu, Baojun Kress, Sara Kothalawala, Dilini M. Kadalayil, Latha Duan, Jiasong Zhang, Hongmei Hadebe, Sabelo Hoffmann, Thomas Jorgenson, Eric Choquet, Hélène Risch, Neil Njølstad, Pål Andreassen, Ole A. Johansson, Stefan Almqvist, Catarina Gong, Tong Ullemar, Vilhelmina Karlsson, Robert Magnusson, Patrik K. E. Szwajda, Agnieszka Burchard, Esteban G. Thyssen, Jacob P. Hansen, Torben Kårhus, Line L. Dantoft, Thomas M. Jeanrenaud, Alexander C.S.N. Ghauri, Ahla Arnold, Andreas Homuth, Georg Lau, Susanne Nöthen, Markus M. Hübner, Norbert Imboden, Medea Visconti, Alessia Falchi, Mario Bataille, Veronique Hysi, Pirro Ballardini, Natalia Boomsma, Dorret I. Hottenga, Jouke J. Müller-Nurasyid, Martina Ahluwalia, Tarunveer S. Stokholm, Jakob Chawes, Bo Schoos, Ann-Marie M. Esplugues, Ana Bustamante, Mariona Raby, Benjamin Arshad, Syed German, Chris Esko, Tõnu Milani, Lili A. Metspalu, Andres Terao, Chikashi Abuabara, Katrina Løset, Mari Hveem, Kristian Jacobsson, Bo Pino-Yanes, Maria Strachan, David P. Grarup, Niels Linneberg, Allan Lee, Young-Ae Probst-Hensch, Nicole Weidinger, Stephan Jarvelin, Marjo-Riitta Melén, Erik Hakonarson, Hakon Irvine, Alan D. Jarvis, Deborah Nijsten, Tamar Duijts, Liesbeth Vonk, Judith M. Koppelmann, Gerard H. Godfrey, Keith M. Barton, Sheila J. Feenstra, Bjarke Pennell, Craig E. Sly, Peter D. Holt, Patrick G. Williams, L. Keoki Bisgaard, Hans Bønnelykke, Klaus Curtin, John Simpson, Angela Murray, Clare Schikowski, Tamara Bunyavanich, Supinda Weiss, Scott T. Holloway, John W. Min, Josine L. Brown, Sara J. Standl, Marie Paternoster, Lavinia Nat Commun Article Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities. Nature Publishing Group UK 2023-10-04 /pmc/articles/PMC10550990/ /pubmed/37794016 http://dx.doi.org/10.1038/s41467-023-41180-2 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Budu-Aggrey, Ashley Kilanowski, Anna Sobczyk, Maria K. Shringarpure, Suyash S. Mitchell, Ruth Reis, Kadri Reigo, Anu Mägi, Reedik Nelis, Mari Tanaka, Nao Brumpton, Ben M. Thomas, Laurent F. Sole-Navais, Pol Flatley, Christopher Espuela-Ortiz, Antonio Herrera-Luis, Esther Lominchar, Jesus V. T. Bork-Jensen, Jette Marenholz, Ingo Arnau-Soler, Aleix Jeong, Ayoung Fawcett, Katherine A. Baurecht, Hansjorg Rodriguez, Elke Alves, Alexessander Couto Kumar, Ashish Sleiman, Patrick M. Chang, Xiao Medina-Gomez, Carolina Hu, Chen Xu, Cheng-jian Qi, Cancan El-Heis, Sarah Titcombe, Philip Antoun, Elie Fadista, João Wang, Carol A. Thiering, Elisabeth Wu, Baojun Kress, Sara Kothalawala, Dilini M. Kadalayil, Latha Duan, Jiasong Zhang, Hongmei Hadebe, Sabelo Hoffmann, Thomas Jorgenson, Eric Choquet, Hélène Risch, Neil Njølstad, Pål Andreassen, Ole A. Johansson, Stefan Almqvist, Catarina Gong, Tong Ullemar, Vilhelmina Karlsson, Robert Magnusson, Patrik K. E. Szwajda, Agnieszka Burchard, Esteban G. Thyssen, Jacob P. Hansen, Torben Kårhus, Line L. Dantoft, Thomas M. Jeanrenaud, Alexander C.S.N. Ghauri, Ahla Arnold, Andreas Homuth, Georg Lau, Susanne Nöthen, Markus M. Hübner, Norbert Imboden, Medea Visconti, Alessia Falchi, Mario Bataille, Veronique Hysi, Pirro Ballardini, Natalia Boomsma, Dorret I. Hottenga, Jouke J. Müller-Nurasyid, Martina Ahluwalia, Tarunveer S. Stokholm, Jakob Chawes, Bo Schoos, Ann-Marie M. Esplugues, Ana Bustamante, Mariona Raby, Benjamin Arshad, Syed German, Chris Esko, Tõnu Milani, Lili A. Metspalu, Andres Terao, Chikashi Abuabara, Katrina Løset, Mari Hveem, Kristian Jacobsson, Bo Pino-Yanes, Maria Strachan, David P. Grarup, Niels Linneberg, Allan Lee, Young-Ae Probst-Hensch, Nicole Weidinger, Stephan Jarvelin, Marjo-Riitta Melén, Erik Hakonarson, Hakon Irvine, Alan D. Jarvis, Deborah Nijsten, Tamar Duijts, Liesbeth Vonk, Judith M. Koppelmann, Gerard H. Godfrey, Keith M. Barton, Sheila J. Feenstra, Bjarke Pennell, Craig E. Sly, Peter D. Holt, Patrick G. Williams, L. Keoki Bisgaard, Hans Bønnelykke, Klaus Curtin, John Simpson, Angela Murray, Clare Schikowski, Tamara Bunyavanich, Supinda Weiss, Scott T. Holloway, John W. Min, Josine L. Brown, Sara J. Standl, Marie Paternoster, Lavinia European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation |
| title | European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation |
| title_full | European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation |
| title_fullStr | European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation |
| title_full_unstemmed | European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation |
| title_short | European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation |
| title_sort | european and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10550990/ https://www.ncbi.nlm.nih.gov/pubmed/37794016 http://dx.doi.org/10.1038/s41467-023-41180-2 |
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europeanandmultiancestrygenomewideassociationmetaanalysisofatopicdermatitishighlightsimportanceofsystemicimmuneregulation |