Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis Maureen D. Mayes, Lara Bossini-Castillo, Olga Gorlova, José Ezequiel.

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Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis Maureen D. Mayes, Lara Bossini-Castillo, Olga Gorlova, José Ezequiel.

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Transcripción de la presentación:

Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis Maureen D. Mayes, Lara Bossini-Castillo, Olga Gorlova, José Ezequiel Martin, Xiaodong Zhou, Wei V. Chen, Shervin Assassi, Jun Ying, Filemon K. Tan, Frank C. Arnett, John D. Reveille, Sandra Guerra, María Teruel, Francisco David Carmona, Peter K. Gregersen, Annette T. Lee, Elena López-Isac, Eguzkine Ochoa, Patricia Carreira, Carmen Pilar Simeón, Iván Castellví, Miguel Ángel González-Gay Norberto Ortego-Centeno, Raquel Ríos, José Luis Callejas, Nuria Navarrete, Rosa García Portales, María Teresa Camps, Antonio Fernández-Nebro, María F. González-Escribano, Julio Sánchez-Román, Francisco José García-Hernández, María Jesús Castillo, María Ángeles Aguirre, Inmaculada Gómez-Gracia, Benjamín Fernández-Gutiérrez, Luis Rodríguez-Rodríguez, Esther Vicente, José Luis Andreu, Mónica Fernández de Castro, Paloma García de la Peña, Francisco Javier López-Longo, Lina Martínez, Vicente Fonollosa, Gerard Espinosa, Carlos Tolosa, Anna Pros, Mónica Rodríguez Carballeira, Francisco Javier Narváez, Manel Rubio Rivas, Vera Ortiz Santamaría, Bernardino Díaz, Luis Trapiella, María del Carmen Freire, Adrián Sousa, María Victoria Egurbide, Patricia Fanlo Mateo, Luis Sáez-Comet, Federico Díaz, Vanesa Hernández, Emma Beltrán, José Andrés Román-Ivorra, Elena Grau, Juan José Alegre Sancho, Francisco J. Blanco García, Natividad Oreiro, Luis Fernández Sueiro, Alexandra Zhernakova, Leonid Padyukov, Marta Alarcón-Riquelme, Cisca Wijmenga, Matthew Brown, Lorenzo Beretta, Gabriela Riemekasten, Torsten Witte, Nicolas Hunzelmann, Alexander Kreuter, Jörg H.W. Distler, Alexandre E. Voskuyl, Annemie J. Schuerwegh, Roger Hesselstrand, Annika Nordin, Paolo Airó, Claudio Lunardi, Paul Shiels, Jacob M. van Laar, Ariane Herrick, Jane Worthington, Christopher Denton, Fredrick M. Wigley, Laura K. Hummers, John Varga, Monique E. Hinchcliff, Murray Baron, Marie Hudson, Janet E. Pope, Daniel E. Furst, Dinesh Khanna, Kristin Phillips, Elena Schiopu, Barbara M. Segal, Jerry A. Molitor, Richard M. Silver, Virginia D. Steen, Robert W. Simms, Robert A. Lafyatis, Barri J. Fessler, Tracy M. Frech, Firas AlKassab, Peter Docherty, Elzbieta Kaminska, Nader Khalidi, Henry Niall Jones, Janet Markland, David Robinson, Jasper Broen, Timothy R.D.J. Radstake, Carmen Fonseca, Bobby P. Koeleman, Javier Martin Maureen D. Mayes, Lara Bossini-Castillo, Olga Gorlova, José Ezequiel Martin, Xiaodong Zhou, Wei V. Chen, Shervin Assassi, Jun Ying, Filemon K. Tan, Frank C. Arnett, John D. Reveille, Sandra Guerra, María Teruel, Francisco David Carmona, Peter K. Gregersen, Annette T. Lee, Elena López- Isac, Eguzkine Ochoa, Patricia Carreira, Carmen Pilar Simeón, Iván Castellví, Miguel Ángel González-Gay Norberto Ortego-Centeno, Raquel Ríos, José Luis Callejas, Nuria Navarrete, Rosa García Portales, María Teresa Camps, Antonio Fernández-Nebro, María F. González-Escribano, Julio Sánchez-Román, Francisco José García-Hernández, María Jesús Castillo, María Ángeles Aguirre, Inmaculada Gómez-Gracia, Benjamín Fernández-Gutiérrez, Luis Rodríguez-Rodríguez, Esther Vicente, José Luis Andreu, Mónica Fernández de Castro, Paloma García de la Peña, Francisco Javier López-Longo, Lina Martínez, Vicente Fonollosa, Gerard Espinosa, Carlos Tolosa, Anna Pros, Mónica Rodríguez Carballeira, Francisco Javier Narváez, Manel Rubio Rivas, Vera Ortiz Santamaría, Bernardino Díaz, Luis Trapiella, María del Carmen Freire, Adrián Sousa, María Victoria Egurbide, Patricia Fanlo Mateo, Luis Sáez- Comet, Federico Díaz, Vanesa Hernández, Emma Beltrán, José Andrés Román-Ivorra, Elena Grau, Juan José Alegre Sancho, Francisco J. Blanco García, Natividad Oreiro, Luis Fernández Sueiro, Alexandra Zhernakova, Leonid Padyukov, Marta Alarcón- Riquelme, Cisca Wijmenga, Matthew Brown, Lorenzo Beretta, Gabriela Riemekasten, Torsten Witte, Nicolas Hunzelmann, Alexander Kreuter, Jörg H.W. Distler, Alexandre E. Voskuyl, Annemie J. Schuerwegh, Roger Hesselstrand, Annika Nordin, Paolo Airó, Claudio Lunardi, Paul Shiels, Jacob M. van Laar, Ariane Herrick, Jane Worthington, Christopher Denton, Fredrick M. Wigley, Laura K. Hummers, John Varga, Monique E. Hinchcliff, Murray Baron, Marie Hudson, Janet E. Pope, Daniel E. Furst, Dinesh Khanna, Kristin Phillips, Elena Schiopu, Barbara M. Segal, Jerry A. Molitor, Richard M. Silver, Virginia D. Steen, Robert W. Simms, Robert A. Lafyatis, Barri J. Fessler, Tracy M. Frech, Firas AlKassab, Peter Docherty, Elzbieta Kaminska, Nader Khalidi, Henry Niall Jones, Janet Markland, David Robinson, Jasper Broen, Timothy R.D.J. Radstake, Carmen Fonseca, Bobby P. Koeleman, Javier Martin The American Journal of Human Genetics Volume 94, Issue 1, Pages 47-61 (January 2014) DOI: 10.1016/j.ajhg.2013.12.002 Copyright © 2014 The American Society of Human Genetics Terms and Conditions

Figure 1 HLA Region: 28,000,000–36,000,000 bp Manhattan plots in which each dot represents the p value of a variant (−log10(p value)) on the vertical axis and the position in chromosome 6 on the horizontal axis. The ACA model comprised HLA-DRβ1 amino acid 13, HLA-DQα1 amino acid 69, and SNPs rs12528892 and rs6933319. The ATA model comprised HLA-DRβ1 amino acids 67 and 86 and HLA-DPβ1 amino acids 76 and 96. The SSc model included the previously described ACA and ATA models and SNPs rs17500468, rs9277052, rs2442719, and rs4713605. The American Journal of Human Genetics 2014 94, 47-61DOI: (10.1016/j.ajhg.2013.12.002) Copyright © 2014 The American Society of Human Genetics Terms and Conditions

Figure 2 Forest Plots Showing the Population-Specific and Pooled Analyses of the Variants at Genome-wide or Suggestive Significance in the SSc versus Control Analysis (A) rs35677470 in DNASE1L3. (B) rs77583790 in the SCHIP1-IL12A locus. (C) rs9373839 in ATG5. (D) rs7130875 in the TREH-DDX6 locus. The American Journal of Human Genetics 2014 94, 47-61DOI: (10.1016/j.ajhg.2013.12.002) Copyright © 2014 The American Society of Human Genetics Terms and Conditions

Figure 3 Regional Plots of the Associations Replicated at Genome-wide Significance in SSc Cases or Different Subgroups in the Overall Meta-analysis after Imputation (A) DNASE1L3 associations in the ACA+ versus control comparison. (B) DNASE1L3 associations in the ACA+ versus control comparison after conditioning on the lead variant (rs35677470). (C) SCHIP1-IL12A locus associations in the lcSSc versus control comparison. (D) SCHIP1-IL12A locus associations in the lcSSc versus control comparison after conditioning on the lead variant (rs77583790). (E) ATG5 associations in the dcSSc versus control comparison. (F) ATG5 associations in the dcSSc versus control comparison after conditioning on the lead variant (rs9373839). p values correspond to the discovery phase. The American Journal of Human Genetics 2014 94, 47-61DOI: (10.1016/j.ajhg.2013.12.002) Copyright © 2014 The American Society of Human Genetics Terms and Conditions