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GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets
Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Cold Spring Harbor Laboratory
2023
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593001/ https://www.ncbi.nlm.nih.gov/pubmed/37873414 http://dx.doi.org/10.1101/2023.10.04.23296543 |
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| author | Dand, Nick Stuart, Philip E Bowes, John Ellinghaus, David Nititham, Joanne Saklatvala, Jake R Teder-Laving, Maris Thomas, Laurent F Traks, Tanel Uebe, Steffen Assmann, Gunter Baudry, David Behrens, Frank Billi, Allison C Brown, Matthew A Burkhardt, Harald Capon, Francesca Chung, Raymond Curtis, Charles J Duckworth, Michael Ellinghaus, Eva FitzGerald, Oliver Gerdes, Sascha Griffiths, Christopher E M Gulliver, Susanne Helliwell, Philip Ho, Pauline Hoffmann, Per Holmen, Oddgeir L Huang, Zhi-ming Hveem, Kristian Jadon, Deepak Köhm, Michaela Kraus, Cornelia Lamacchia, Céline Lee, Sang Hyuck Ma, Feiyang Mahil, Satveer K McHugh, Neil McManus, Ross Modalsli, Ellen H Nissen, Michael J Nöthen, Markus Oji, Vinzenz Oksenberg, Jorge R Patrick, Matthew T Perez-White, Bethany E Ramming, Andreas Rech, Jürgen Rosen, Cheryl Sarkar, Mrinal K Schett, Georg Schmidt, Börge Tejasvi, Trilokraj Traupe, Heiko Voorhees, John J Wacker, Eike Matthias Warren, Richard B Wasikowski, Rachael Weidinger, Stephan Wen, Xiaoquan Zhang, Zhaolin Barton, Anne Chandran, Vinod Esko, Tõnu Foerster, John Franke, Andre Gladman, Dafna D Gudjonsson, Johann E Gulliver, Wayne Hüffmeier, Ulrike Kingo, Külli Kõks, Sulev Liao, Wilson Løset, Mari Mägi, Reedik Nair, Rajan P Rahman, Proton Reis, André Smith, Catherine H Di Meglio, Paola Barker, Jonathan N Tsoi, Lam C Simpson, Michael A Elder, James T |
| author_facet | Dand, Nick Stuart, Philip E Bowes, John Ellinghaus, David Nititham, Joanne Saklatvala, Jake R Teder-Laving, Maris Thomas, Laurent F Traks, Tanel Uebe, Steffen Assmann, Gunter Baudry, David Behrens, Frank Billi, Allison C Brown, Matthew A Burkhardt, Harald Capon, Francesca Chung, Raymond Curtis, Charles J Duckworth, Michael Ellinghaus, Eva FitzGerald, Oliver Gerdes, Sascha Griffiths, Christopher E M Gulliver, Susanne Helliwell, Philip Ho, Pauline Hoffmann, Per Holmen, Oddgeir L Huang, Zhi-ming Hveem, Kristian Jadon, Deepak Köhm, Michaela Kraus, Cornelia Lamacchia, Céline Lee, Sang Hyuck Ma, Feiyang Mahil, Satveer K McHugh, Neil McManus, Ross Modalsli, Ellen H Nissen, Michael J Nöthen, Markus Oji, Vinzenz Oksenberg, Jorge R Patrick, Matthew T Perez-White, Bethany E Ramming, Andreas Rech, Jürgen Rosen, Cheryl Sarkar, Mrinal K Schett, Georg Schmidt, Börge Tejasvi, Trilokraj Traupe, Heiko Voorhees, John J Wacker, Eike Matthias Warren, Richard B Wasikowski, Rachael Weidinger, Stephan Wen, Xiaoquan Zhang, Zhaolin Barton, Anne Chandran, Vinod Esko, Tõnu Foerster, John Franke, Andre Gladman, Dafna D Gudjonsson, Johann E Gulliver, Wayne Hüffmeier, Ulrike Kingo, Külli Kõks, Sulev Liao, Wilson Løset, Mari Mägi, Reedik Nair, Rajan P Rahman, Proton Reis, André Smith, Catherine H Di Meglio, Paola Barker, Jonathan N Tsoi, Lam C Simpson, Michael A Elder, James T |
| author_sort | Dand, Nick |
| collection | PubMed |
| description | Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci. To move towards a saturation map of psoriasis susceptibility we meta-analysed 18 GWAS comprising 36,466 cases and 458,078 controls and identified 109 distinct psoriasis susceptibility loci, including 45 that have not been previously reported. These include susceptibility variants at loci in which the therapeutic targets IL17RA and AHR are encoded, and deleterious coding variants supporting potential new drug targets (including in STAP2, CPVL and POU2F3). We conducted a transcriptome-wide association study to identify regulatory effects of psoriasis susceptibility variants and cross-referenced these against single cell expression profiles in psoriasis-affected skin, highlighting roles for the transcriptional regulation of haematopoietic cell development and epigenetic modulation of interferon signalling in psoriasis pathobiology. |
| format | Online Article Text |
| id | pubmed-10593001 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2023 |
| publisher | Cold Spring Harbor Laboratory |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-105930012023-10-24 GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets Dand, Nick Stuart, Philip E Bowes, John Ellinghaus, David Nititham, Joanne Saklatvala, Jake R Teder-Laving, Maris Thomas, Laurent F Traks, Tanel Uebe, Steffen Assmann, Gunter Baudry, David Behrens, Frank Billi, Allison C Brown, Matthew A Burkhardt, Harald Capon, Francesca Chung, Raymond Curtis, Charles J Duckworth, Michael Ellinghaus, Eva FitzGerald, Oliver Gerdes, Sascha Griffiths, Christopher E M Gulliver, Susanne Helliwell, Philip Ho, Pauline Hoffmann, Per Holmen, Oddgeir L Huang, Zhi-ming Hveem, Kristian Jadon, Deepak Köhm, Michaela Kraus, Cornelia Lamacchia, Céline Lee, Sang Hyuck Ma, Feiyang Mahil, Satveer K McHugh, Neil McManus, Ross Modalsli, Ellen H Nissen, Michael J Nöthen, Markus Oji, Vinzenz Oksenberg, Jorge R Patrick, Matthew T Perez-White, Bethany E Ramming, Andreas Rech, Jürgen Rosen, Cheryl Sarkar, Mrinal K Schett, Georg Schmidt, Börge Tejasvi, Trilokraj Traupe, Heiko Voorhees, John J Wacker, Eike Matthias Warren, Richard B Wasikowski, Rachael Weidinger, Stephan Wen, Xiaoquan Zhang, Zhaolin Barton, Anne Chandran, Vinod Esko, Tõnu Foerster, John Franke, Andre Gladman, Dafna D Gudjonsson, Johann E Gulliver, Wayne Hüffmeier, Ulrike Kingo, Külli Kõks, Sulev Liao, Wilson Løset, Mari Mägi, Reedik Nair, Rajan P Rahman, Proton Reis, André Smith, Catherine H Di Meglio, Paola Barker, Jonathan N Tsoi, Lam C Simpson, Michael A Elder, James T medRxiv Article Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci. To move towards a saturation map of psoriasis susceptibility we meta-analysed 18 GWAS comprising 36,466 cases and 458,078 controls and identified 109 distinct psoriasis susceptibility loci, including 45 that have not been previously reported. These include susceptibility variants at loci in which the therapeutic targets IL17RA and AHR are encoded, and deleterious coding variants supporting potential new drug targets (including in STAP2, CPVL and POU2F3). We conducted a transcriptome-wide association study to identify regulatory effects of psoriasis susceptibility variants and cross-referenced these against single cell expression profiles in psoriasis-affected skin, highlighting roles for the transcriptional regulation of haematopoietic cell development and epigenetic modulation of interferon signalling in psoriasis pathobiology. Cold Spring Harbor Laboratory 2023-10-05 /pmc/articles/PMC10593001/ /pubmed/37873414 http://dx.doi.org/10.1101/2023.10.04.23296543 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
| spellingShingle | Article Dand, Nick Stuart, Philip E Bowes, John Ellinghaus, David Nititham, Joanne Saklatvala, Jake R Teder-Laving, Maris Thomas, Laurent F Traks, Tanel Uebe, Steffen Assmann, Gunter Baudry, David Behrens, Frank Billi, Allison C Brown, Matthew A Burkhardt, Harald Capon, Francesca Chung, Raymond Curtis, Charles J Duckworth, Michael Ellinghaus, Eva FitzGerald, Oliver Gerdes, Sascha Griffiths, Christopher E M Gulliver, Susanne Helliwell, Philip Ho, Pauline Hoffmann, Per Holmen, Oddgeir L Huang, Zhi-ming Hveem, Kristian Jadon, Deepak Köhm, Michaela Kraus, Cornelia Lamacchia, Céline Lee, Sang Hyuck Ma, Feiyang Mahil, Satveer K McHugh, Neil McManus, Ross Modalsli, Ellen H Nissen, Michael J Nöthen, Markus Oji, Vinzenz Oksenberg, Jorge R Patrick, Matthew T Perez-White, Bethany E Ramming, Andreas Rech, Jürgen Rosen, Cheryl Sarkar, Mrinal K Schett, Georg Schmidt, Börge Tejasvi, Trilokraj Traupe, Heiko Voorhees, John J Wacker, Eike Matthias Warren, Richard B Wasikowski, Rachael Weidinger, Stephan Wen, Xiaoquan Zhang, Zhaolin Barton, Anne Chandran, Vinod Esko, Tõnu Foerster, John Franke, Andre Gladman, Dafna D Gudjonsson, Johann E Gulliver, Wayne Hüffmeier, Ulrike Kingo, Külli Kõks, Sulev Liao, Wilson Løset, Mari Mägi, Reedik Nair, Rajan P Rahman, Proton Reis, André Smith, Catherine H Di Meglio, Paola Barker, Jonathan N Tsoi, Lam C Simpson, Michael A Elder, James T GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets |
| title | GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets |
| title_full | GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets |
| title_fullStr | GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets |
| title_full_unstemmed | GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets |
| title_short | GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets |
| title_sort | gwas meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593001/ https://www.ncbi.nlm.nih.gov/pubmed/37873414 http://dx.doi.org/10.1101/2023.10.04.23296543 |
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