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1. Molecular characterisation of lupus low disease activity state (LLDAS) and DORIS remission by whole-blood transcriptome-based pathways in a pan-European systemic lupus erythematosus cohort

Author: Parodis, Ioannis, Lindblom, Julius, Barturen, Guillermo, Ortega-Castro, Rafaela, Cervera, Ricard, Pers, Jacques-Olivier, Genre, Fernanda, Hiepe, Falk, Gerosa, Maria, Kovács, László, De Langhe, Ellen, Piantoni, Silvia, Stummvoll, Georg, Vasconcelos, Carlos, Vigone, Barbara, Witte, Torsten, Alarcón-Riquelme, Marta E., Beretta, Lorenzo, Parodis, Ioannis, Lindblom, Julius, Barturen, Guillermo, Ortega-Castro, Rafaela, Cervera, Ricard, Pers, Jacques-Olivier, Genre, Fernanda, Hiepe, Falk, Gerosa, Maria, Kovács, László, De Langhe, Ellen, Piantoni, Silvia, Stummvoll, Georg, Vasconcelos, Carlos, Vigone, Barbara, Witte, Torsten, Alarcón-Riquelme, Marta E., and Beretta, Lorenzo
Abstract: OBJECTIVES: To unveil biological milieus underlying low disease activity (LDA) and remission versus active systemic lupus erythematosus (SLE). METHODS: We determined differentially expressed pathways (DEPs) in SLE patients from the PRECISESADS project (NTC02890121) stratified into patients fulfilling and not fulfilling the criteria of (1) Lupus LDA State (LLDAS), (2) Definitions of Remission in SLE remission, and (3) LLDAS exclusive of remission. RESULTS: We analysed data from 321 patients; 40.8% were in LLDAS, and 17.4% in DORIS remission. After exclusion of patients in remission, 28.3% were in LLDAS. Overall, 604 pathways differed significantly in LLDAS versus non-LLDAS patients with an false-discovery rate-corrected p (q)<0.05 and a robust effect size (dr)≥0.36. Accordingly, 288 pathways differed significantly between DORIS remitters and non-remitters (q<0.05 and dr≥0.36). DEPs yielded distinct molecular clusters characterised by differential serological, musculoskeletal, and renal activity. Analysis of partially overlapping samples showed no DEPs between LLDAS and DORIS remission. Drug repurposing potentiality for treating SLE was unveiled, as were important pathways underlying active SLE whose modulation could aid attainment of LLDAS/remission, including toll-like receptor (TLR) cascades, Bruton tyrosine kinase (BTK) activity, the cytotoxic T lymphocyte antigen 4 (CTLA-4)-related inhibitory signalling, and the nucleotide-binding oligomerization domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome pathway. CONCLUSIONS: We demonstrated for the first time molecular signalling pathways distinguishing LLDAS/remission from active SLE. LLDAS/remission was associated with reversal of biological processes related to SLE pathogenesis and specific clinical manifestations. DEP clustering by remission better grouped patients compared with LLDAS, substantiating remission as the ultimate treatment goal in SLE; however, the lack of substantial pathway dif, IP has received grants from the Swedish Rheumatism Association (R-969696), King Gustaf V’s 80-year Foundation (FAI-2020-0741), Swedish Society of Medicine (SLS-974449), Nyckelfonden (OLL-974804), Professor Nanna Svartz Foundation (2021-00436), Ulla and Roland Gustafsson Foundation (2021-26), Region Stockholm (FoUI-955483), and Karolinska Institute. This work was supported by EU/EFPIA/Innovative Medicines Initiative (IMI) Joint Undertaking (JU) PRECISESADS grant no. 115565 and IMI 2 JU (now HIH) 3TR grant no. 831434, and Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy, EXC 2155, project no. 390874280.
Published: 2024
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2. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Author: Barturen, Guillermo, Babaei, Sepideh, Catala-Moll, Francesc, Martinez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugan, Jordi, Carmona-Saez, Pedro, Toro-Dominguez, Daniel, Carnero-Montoro, Elena, Teruel, Maria, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodriguez-Ubreva, Javier, Garcia-Gomez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Maranon, Concepcion, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocio, Garrancho, Francisco Javier, Lopez-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Hector, Almeida, Isabel, Azevedo, Nancy, Brandao, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fatima, Marinho, Antonio, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martinez, Alfonso, Genre, Fernanda, Lopez Mejias, Raquel, Gonzalez-Gay, Miguel A., Remuzgo, Sara, Ubilla Garcia, Begona, Cervera, Ricard, Espinosa, Gerard, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Diaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernandez Roldan, Maria Concepcion, Jimenez Gomez, Yolanda, Jimenez Moleon, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurelie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valerie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouviere, Benedicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, Chizzolini, Carlo, Dufour, Aleksandra, Wynar, Donatienne, Balog, Attila, Bocskai, Marta, Deak, Magdolna, Dulic, Sonja, Kadar, Gabriella, Kovacs, Laszlo, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Benschop, Robert J., Chamberlain, Chris, Dow, Ernst R., Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegard, Johan, Martin, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, Alarcon-Riquelme, Marta E., Barturen, Guillermo, Babaei, Sepideh, Catala-Moll, Francesc, Martinez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugan, Jordi, Carmona-Saez, Pedro, Toro-Dominguez, Daniel, Carnero-Montoro, Elena, Teruel, Maria, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodriguez-Ubreva, Javier, Garcia-Gomez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Maranon, Concepcion, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocio, Garrancho, Francisco Javier, Lopez-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Hector, Almeida, Isabel, Azevedo, Nancy, Brandao, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fatima, Marinho, Antonio, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martinez, Alfonso, Genre, Fernanda, Lopez Mejias, Raquel, Gonzalez-Gay, Miguel A., Remuzgo, Sara, Ubilla Garcia, Begona, Cervera, Ricard, Espinosa, Gerard, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Diaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernandez Roldan, Maria Concepcion, Jimenez Gomez, Yolanda, Jimenez Moleon, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurelie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valerie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouviere, Benedicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, Chizzolini, Carlo, Dufour, Aleksandra, Wynar, Donatienne, Balog, Attila, Bocskai, Marta, Deak, Magdolna, Dulic, Sonja, Kadar, Gabriella, Kovacs, Laszlo, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Benschop, Robert J., Chamberlain, Chris, Dow, Ernst R., Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegard, Johan, Martin, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, and Alarcon-Riquelme, Marta E.
Abstract: Objective Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. Methods Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. Results Four clusters were identified and validated. Three were pathologic, representing inflammatory, lymphoid, and interferon patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. Conclusion Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases.
Published: 2021

3. A new molecular classification to drive precision treatment strategies in primary Sjogren's syndrome

Author: Soret, Perrine, Le Dantec, Christelle, Desvaux, Emiko, Foulquier, Nathan, Chassagnol, Bastien, Hubert, Sandra, Jamin, Christophe, Barturen, Guillermo, Desachy, Guillaume, Devauchelle-Pensec, Valerie, Boudjeniba, Cheiema, Cornec, Divi, Saraux, Alain, Jousse-Joulin, Sandrine, Barbarroja, Nuria, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Beretta, Lorenzo, Chizzolini, Carlo, Kovacs, Laszlo, Witte, Torsten, Bettacchioli, Eleonore, Buttgereit, Anne, Makowska, Zuzanna, Lesche, Ralf, Orietta Borghi, Maria, Martin, Javier, Courtade-Gaiani, Sophie, Xuereb, Laura, Guedj, Mickael, Moingeon, Philippe, Alarcon-Riquelme, Marta E., Laigle, Laurence, Pers, Jacques-Olivier, Vigone, Barbara, Lauwerys, Bernard, Ducreux, Julie, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Neves, Esmeralda, Faria, Raquel, Brandao, Mariana, Campar, Ana, Marinho, Antonio, Farinha, Fatima, Almeida, Isabel, Gonzalez-Gay Mantecon, Miguel Angel, Alonso, Ricardo Blanco, Martinez, Alfonso Corrales, Cervera, Ricard, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Angeles Aguirre-Zamorano, Ma, Carmen Castro-Villegas, Ma, Jimenez Gomez, Yolanda, Ortego, Norberto, Fernandez Roldan, Maria Concepcion, Raya, Enrique, Moleon, Inmaculada Jimenez, de Ramon, Enrique, Quintero, Isabel Diaz, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Dulic, Sonja, Kadar, Gabriella, Hiepe, Falk, Gerl, Velia, Thiel, Silvia, Maresca, Manuel Rodriguez, Lopez-Berrio, Antonio, Aguilar-Quesada, Rocio, Navarro-Linares, Hector, Ioannou, Yiannis, Chamberlain, Chris, Marovac, Jacqueline, Alarcon Riquelme, Marta, Gomes Anjos, Tania, Maranon, Concepcion, Le Lann, Lucas, Simon, Quentin, Rouviere, Benedicte, Varela, Nieves, Muchmore, Brian, Dufour, Aleksandra, Alvarez, Montserrat, Cremer, Jonathan, Lopez-Pedrera, Chary, Ger, Velia, Khodadadi, Laleh, Cheng, Qingyu, De Groof, Aurelie, Trombetta, Elena, Li, Tianlu, Alvarez-Errico, Damiana, Kniesch, Katja, Azevedo, Nancy, Rao, Sambasiva, Jouve, Pierre-Emmanuel, Soret, Perrine, Le Dantec, Christelle, Desvaux, Emiko, Foulquier, Nathan, Chassagnol, Bastien, Hubert, Sandra, Jamin, Christophe, Barturen, Guillermo, Desachy, Guillaume, Devauchelle-Pensec, Valerie, Boudjeniba, Cheiema, Cornec, Divi, Saraux, Alain, Jousse-Joulin, Sandrine, Barbarroja, Nuria, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Beretta, Lorenzo, Chizzolini, Carlo, Kovacs, Laszlo, Witte, Torsten, Bettacchioli, Eleonore, Buttgereit, Anne, Makowska, Zuzanna, Lesche, Ralf, Orietta Borghi, Maria, Martin, Javier, Courtade-Gaiani, Sophie, Xuereb, Laura, Guedj, Mickael, Moingeon, Philippe, Alarcon-Riquelme, Marta E., Laigle, Laurence, Pers, Jacques-Olivier, Vigone, Barbara, Lauwerys, Bernard, Ducreux, Julie, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Neves, Esmeralda, Faria, Raquel, Brandao, Mariana, Campar, Ana, Marinho, Antonio, Farinha, Fatima, Almeida, Isabel, Gonzalez-Gay Mantecon, Miguel Angel, Alonso, Ricardo Blanco, Martinez, Alfonso Corrales, Cervera, Ricard, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Angeles Aguirre-Zamorano, Ma, Carmen Castro-Villegas, Ma, Jimenez Gomez, Yolanda, Ortego, Norberto, Fernandez Roldan, Maria Concepcion, Raya, Enrique, Moleon, Inmaculada Jimenez, de Ramon, Enrique, Quintero, Isabel Diaz, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Dulic, Sonja, Kadar, Gabriella, Hiepe, Falk, Gerl, Velia, Thiel, Silvia, Maresca, Manuel Rodriguez, Lopez-Berrio, Antonio, Aguilar-Quesada, Rocio, Navarro-Linares, Hector, Ioannou, Yiannis, Chamberlain, Chris, Marovac, Jacqueline, Alarcon Riquelme, Marta, Gomes Anjos, Tania, Maranon, Concepcion, Le Lann, Lucas, Simon, Quentin, Rouviere, Benedicte, Varela, Nieves, Muchmore, Brian, Dufour, Aleksandra, Alvarez, Montserrat, Cremer, Jonathan, Lopez-Pedrera, Chary, Ger, Velia, Khodadadi, Laleh, Cheng, Qingyu, De Groof, Aurelie, Trombetta, Elena, Li, Tianlu, Alvarez-Errico, Damiana, Kniesch, Katja, Azevedo, Nancy, Rao, Sambasiva, and Jouve, Pierre-Emmanuel
Abstract: There is currently no approved treatment for primary Sjogren's syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjogren's syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials. Sjogren's syndrome, a disease that primarily affects women, is poorly understood. Here, the authors combine data from a large cohort of patients and healthy controls to identify biomarkers that distinguish patient subgroups to improve our understanding of the disease and facilitate drug development.
Published: 2021

4. 2021 DORIS definition of remission in SLE: final recommendations from an international task force.

Author: UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, van Vollenhoven, Ronald F, Bertsias, George, Doria, Andrea, Isenberg, David, Morand, Eric, Petri, Michelle A, Pons-Estel, Bernardo A, Rahman, Anisur, Ugarte-Gil, Manuel Francisco, Voskuyl, Alexandre, Arnaud, Laurent, Bruce, Ian N, Cervera, Ricard, Costedoat-Chalumeau, Nathalie, Gordon, Caroline, Houssiau, Frédéric, Mosca, Marta, Schneider, Matthias, Ward, Michael M, Alarcon, Graciela, Aringer, Martin, Askenase, Anka, Bae, Sang-Cheol, Bootsma, Hendrika, Boumpas, Dimitrios T, Brunner, Hermine, Clarke, Ann Elaine, Coney, Cindy, Czirják, László, Dörner, Thomas, Faria, Raquel, Fischer, Rebecca, Fritsch-Stork, Ruth, Inanc, Murat, Jacobsen, Søren, Jayne, David, Kuhn, Annegret, van Leeuw, Bernadette, Limper, Maarten, Mariette, Xavier, Navarra, Sandra, Nikpour, Mandana, Olesinska, Marzena Helena, Pons-Estel, Guillermo, Romero-Diaz, Juanita, Rubio, Blanca, Schoenfeld, Yehuda, Bonfá, Eloisa, Smolen, Josef, Teng, Y K Onno, Tincani, Angela, Tsang-A-Sjoe, Michel, Vasconcelos, Carlos, Voss, Anne, Werth, Victoria P, Zakharhova, Elena, Aranow, Cynthia, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, van Vollenhoven, Ronald F, Bertsias, George, Doria, Andrea, Isenberg, David, Morand, Eric, Petri, Michelle A, Pons-Estel, Bernardo A, Rahman, Anisur, Ugarte-Gil, Manuel Francisco, Voskuyl, Alexandre, Arnaud, Laurent, Bruce, Ian N, Cervera, Ricard, Costedoat-Chalumeau, Nathalie, Gordon, Caroline, Houssiau, Frédéric, Mosca, Marta, Schneider, Matthias, Ward, Michael M, Alarcon, Graciela, Aringer, Martin, Askenase, Anka, Bae, Sang-Cheol, Bootsma, Hendrika, Boumpas, Dimitrios T, Brunner, Hermine, Clarke, Ann Elaine, Coney, Cindy, Czirják, László, Dörner, Thomas, Faria, Raquel, Fischer, Rebecca, Fritsch-Stork, Ruth, Inanc, Murat, Jacobsen, Søren, Jayne, David, Kuhn, Annegret, van Leeuw, Bernadette, Limper, Maarten, Mariette, Xavier, Navarra, Sandra, Nikpour, Mandana, Olesinska, Marzena Helena, Pons-Estel, Guillermo, Romero-Diaz, Juanita, Rubio, Blanca, Schoenfeld, Yehuda, Bonfá, Eloisa, Smolen, Josef, Teng, Y K Onno, Tincani, Angela, Tsang-A-Sjoe, Michel, Vasconcelos, Carlos, Voss, Anne, Werth, Victoria P, Zakharhova, Elena, and Aranow, Cynthia
Abstract: OBJECTIVE: To achieve consensus on a definition of remission in SLE (DORIS). BACKGROUND: Remission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a framework for such a definition, without reaching a final recommendation. METHODS: Several systematic literature reviews were performed and specific research questions examined in suitably chosen data sets. The findings were discussed, reformulated as recommendations and voted on. RESULTS: Based on data from the literature and several SLE-specific data sets, a set of recommendations was endorsed. Ultimately, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical systemic lupus erythematosus disease activitiy index (SLEDAI)=0, Evaluator's Global Assessment <0.5 (0-3), prednisolone 5 mg/day or less, and stable antimalarials, immunosuppressives, and biologics. CONCLUSION: The 2021 DORIS definition of remission in SLE is recommended for use in clinical care, education, and research including clinical trials and observational studies.
Published: 2021

5. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases.

Author: UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alarcón-Riquelme, Marta E, Benschop, Robert J, Balog, Attila, Bocskai, Márta, Deák, Magdolna, Dulic, Sonja, Kádár, Gabriella, Kovács, László, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Chamberlain, Chris, Dufour, Aleksandra, Dow, Ernst R, Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegård, Johan, Martín, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, Wynar, Donatienne, Barturen, Guillermo, Babaei, Sepideh, Català-Moll, Francesc, Martínez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugán, Jordi, Carmona-Sáez, Pedro, Toro-Domínguez, Daniel, Carnero-Montoro, Elena, Teruel, María, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodríguez-Ubreva, Javier, García-Gómez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Marañón, Concepción, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocío, Garrancho, Francisco Javier, López-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Héctor, Almeida, Isabel, Azevedo, Nancy, Brandão, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fátima, Marinho, António, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Genre, Fernanda, López Mejías, Raquel, Gonzalez-Gay, Miguel A, Remuzgo, Sara, Ubilla Garcia, Begoña, Cervera, Ricard, Espinosa, Gerard, Rodríguez-Pintó, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Díaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernández Roldán, María Concepción, Jiménez Gómez, Yolanda, Jiménez Moleón, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurélie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valérie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouvière, Bénédicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, Chizzolini, Carlo, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alarcón-Riquelme, Marta E, Benschop, Robert J, Balog, Attila, Bocskai, Márta, Deák, Magdolna, Dulic, Sonja, Kádár, Gabriella, Kovács, László, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Chamberlain, Chris, Dufour, Aleksandra, Dow, Ernst R, Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegård, Johan, Martín, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, Wynar, Donatienne, Barturen, Guillermo, Babaei, Sepideh, Català-Moll, Francesc, Martínez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugán, Jordi, Carmona-Sáez, Pedro, Toro-Domínguez, Daniel, Carnero-Montoro, Elena, Teruel, María, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodríguez-Ubreva, Javier, García-Gómez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Marañón, Concepción, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocío, Garrancho, Francisco Javier, López-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Héctor, Almeida, Isabel, Azevedo, Nancy, Brandão, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fátima, Marinho, António, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Genre, Fernanda, López Mejías, Raquel, Gonzalez-Gay, Miguel A, Remuzgo, Sara, Ubilla Garcia, Begoña, Cervera, Ricard, Espinosa, Gerard, Rodríguez-Pintó, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Díaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernández Roldán, María Concepción, Jiménez Gómez, Yolanda, Jiménez Moleón, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurélie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valérie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouvière, Bénédicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, and Chizzolini, Carlo
Abstract: OBJECTIVE: Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. METHODS: Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. RESULTS: Four clusters were identified and validated. Three were pathologic, representing "inflammatory," "lymphoid," and "interferon" patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. CONCLUSION: Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases.
Published: 2021

6. Jogo didático no ensino de conceitos lean na disciplina de administração de obras: relato de experiência

Author: Viana, Marina Ribeiro, Santos, Débora de Gois, Vasconcelos, Carlos Alberto, Viana, Marina Ribeiro, Santos, Débora de Gois, and Vasconcelos, Carlos Alberto
Abstract: A mentalidade enxuta visa reduzir ou eliminar as atividades que não agregam valor ao produto através de melhorias contínuas e da redução de perdas. Trata-se de uma filosofia originada na década de 1990 e que, aos poucos, foi incorporada aos currículos dos cursos de Engenharia de Produção e Civil. Sob esse aspecto, por entender que a utilização de jogos didáticos pode ser eficiente, ao passo que estimula a participação e motiva os envolvidos, buscou-se investigar a utilização desse recurso pedagógico na difusão dos conceitos Lean entre futuros profissionais do setor. Diante do exposto, o presente trabalho originou-se de uma experiência com a aplicação do jogo Fábrica de Canetas em uma turma da graduação em Engenharia Civil. Para tal, foram realizadas simulações que permitiram abordar conceitos relativos à Produção Enxuta e ao gerenciamento da produção e, ao final, foi solicitado, aos integrantes dos grupos, a elaboração de um relatório sobre o que foi aprendido. Após a aplicação do jogo, foi possível observar maior participação dos discentes ao desenvolverem as atividades e ao comentar sobre os aspectos positivos e o que poderiam ser melhorados. Conclui-se, portanto, que os jogos podem auxiliar no ensino de teorias, sendo complementar ao que outrora fora visto em sala de aula.
Published: 2021

7. European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance

Author: Aringer, Martin, Brinks, Ralph, Dörner, Thomas, Daikh, David, Mosca, Marta, Ramsey-Goldman, Rosalind, Smolen, Josef S., Wofsy, David, Boumpas, Dimitrios T., Kamen, Diane L., Jayne, David, Cervera, R., Costedoat-Chalumeau, Nathalie, Diamond, Betty, Gladman, Dafna D., Hahn, Bevra, Hiepe, Falk, Jacobsen, Søren, Khanna, Dinesh, Lerstrøm, Kirsten, Massarotti, Elena, McCune, Joseph, Ruiz-Irastorza, Guillermo, Sanchez-Guerrero, Jorge, Schneider, Matthias, Urowitz, Murray, Bertsias, George, Hoyer, Bimba F., Leuchten, Nicolai, Schmajuk, Gabriela, Tani, Chiara, Tedeschi, Sara K., Touma, Zahi, Anic, Branimir, Assan, Florence, Chan, Tak Mao, Clarke, Ann Elaine, Crow, Mary K., Czirják, László, Doria, Andrea, Graninger, Winfried, Halda-Kiss, Bernadett, Hasni, Sarfaraz, Izmirly, Peter M., Jung, Michelle, Kumánovics, Gábor, Mariette, Xavier, Padjen, Ivan, Pego-Reigosa, José M., Romero-Diaz, Juanita, Rúa-Figueroa, Íñigo, Seror, Raphaèle, Stummvoll, Georg H., Tanaka, Yoshiya, Tektonidou, Maria G., Vasconcelos, Carlos, Vital, Edward M., Wallace, Daniel J., Yavuz, Sule, Meroni, Pier Luigi, Fritzler, Marvin J., Naden, Ray, Costenbader, Karen, Johnson, Sindhu R., Aringer, Martin, Brinks, Ralph, Dörner, Thomas, Daikh, David, Mosca, Marta, Ramsey-Goldman, Rosalind, Smolen, Josef S., Wofsy, David, Boumpas, Dimitrios T., Kamen, Diane L., Jayne, David, Cervera, R., Costedoat-Chalumeau, Nathalie, Diamond, Betty, Gladman, Dafna D., Hahn, Bevra, Hiepe, Falk, Jacobsen, Søren, Khanna, Dinesh, Lerstrøm, Kirsten, Massarotti, Elena, McCune, Joseph, Ruiz-Irastorza, Guillermo, Sanchez-Guerrero, Jorge, Schneider, Matthias, Urowitz, Murray, Bertsias, George, Hoyer, Bimba F., Leuchten, Nicolai, Schmajuk, Gabriela, Tani, Chiara, Tedeschi, Sara K., Touma, Zahi, Anic, Branimir, Assan, Florence, Chan, Tak Mao, Clarke, Ann Elaine, Crow, Mary K., Czirják, László, Doria, Andrea, Graninger, Winfried, Halda-Kiss, Bernadett, Hasni, Sarfaraz, Izmirly, Peter M., Jung, Michelle, Kumánovics, Gábor, Mariette, Xavier, Padjen, Ivan, Pego-Reigosa, José M., Romero-Diaz, Juanita, Rúa-Figueroa, Íñigo, Seror, Raphaèle, Stummvoll, Georg H., Tanaka, Yoshiya, Tektonidou, Maria G., Vasconcelos, Carlos, Vital, Edward M., Wallace, Daniel J., Yavuz, Sule, Meroni, Pier Luigi, Fritzler, Marvin J., Naden, Ray, Costenbader, Karen, and Johnson, Sindhu R.
Abstract: Background/objectives The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. Methods We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. Results Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement. Conclusions Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.
Published: 2021

8. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Author: Barturen, Guillermo, Babaei, Sepideh, Catala-Moll, Francesc, Martinez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugan, Jordi, Carmona-Saez, Pedro, Toro-Dominguez, Daniel, Carnero-Montoro, Elena, Teruel, Maria, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodriguez-Ubreva, Javier, Garcia-Gomez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Maranon, Concepcion, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocio, Garrancho, Francisco Javier, Lopez-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Hector, Almeida, Isabel, Azevedo, Nancy, Brandao, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fatima, Marinho, Antonio, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martinez, Alfonso, Genre, Fernanda, Lopez Mejias, Raquel, Gonzalez-Gay, Miguel A., Remuzgo, Sara, Ubilla Garcia, Begona, Cervera, Ricard, Espinosa, Gerard, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Diaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernandez Roldan, Maria Concepcion, Jimenez Gomez, Yolanda, Jimenez Moleon, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurelie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valerie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouviere, Benedicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, Chizzolini, Carlo, Dufour, Aleksandra, Wynar, Donatienne, Balog, Attila, Bocskai, Marta, Deak, Magdolna, Dulic, Sonja, Kadar, Gabriella, Kovacs, Laszlo, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Benschop, Robert J., Chamberlain, Chris, Dow, Ernst R., Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegard, Johan, Martin, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, Alarcon-Riquelme, Marta E., Barturen, Guillermo, Babaei, Sepideh, Catala-Moll, Francesc, Martinez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugan, Jordi, Carmona-Saez, Pedro, Toro-Dominguez, Daniel, Carnero-Montoro, Elena, Teruel, Maria, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodriguez-Ubreva, Javier, Garcia-Gomez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Maranon, Concepcion, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocio, Garrancho, Francisco Javier, Lopez-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Hector, Almeida, Isabel, Azevedo, Nancy, Brandao, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fatima, Marinho, Antonio, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martinez, Alfonso, Genre, Fernanda, Lopez Mejias, Raquel, Gonzalez-Gay, Miguel A., Remuzgo, Sara, Ubilla Garcia, Begona, Cervera, Ricard, Espinosa, Gerard, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Diaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernandez Roldan, Maria Concepcion, Jimenez Gomez, Yolanda, Jimenez Moleon, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurelie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valerie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouviere, Benedicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, Chizzolini, Carlo, Dufour, Aleksandra, Wynar, Donatienne, Balog, Attila, Bocskai, Marta, Deak, Magdolna, Dulic, Sonja, Kadar, Gabriella, Kovacs, Laszlo, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Benschop, Robert J., Chamberlain, Chris, Dow, Ernst R., Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegard, Johan, Martin, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, and Alarcon-Riquelme, Marta E.
Abstract: Objective Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. Methods Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. Results Four clusters were identified and validated. Three were pathologic, representing inflammatory, lymphoid, and interferon patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. Conclusion Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases.
Published: 2021

9. A new molecular classification to drive precision treatment strategies in primary Sjogren's syndrome

Author: Soret, Perrine, Le Dantec, Christelle, Desvaux, Emiko, Foulquier, Nathan, Chassagnol, Bastien, Hubert, Sandra, Jamin, Christophe, Barturen, Guillermo, Desachy, Guillaume, Devauchelle-Pensec, Valerie, Boudjeniba, Cheiema, Cornec, Divi, Saraux, Alain, Jousse-Joulin, Sandrine, Barbarroja, Nuria, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Beretta, Lorenzo, Chizzolini, Carlo, Kovacs, Laszlo, Witte, Torsten, Bettacchioli, Eleonore, Buttgereit, Anne, Makowska, Zuzanna, Lesche, Ralf, Orietta Borghi, Maria, Martin, Javier, Courtade-Gaiani, Sophie, Xuereb, Laura, Guedj, Mickael, Moingeon, Philippe, Alarcon-Riquelme, Marta E., Laigle, Laurence, Pers, Jacques-Olivier, Vigone, Barbara, Lauwerys, Bernard, Ducreux, Julie, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Neves, Esmeralda, Faria, Raquel, Brandao, Mariana, Campar, Ana, Marinho, Antonio, Farinha, Fatima, Almeida, Isabel, Gonzalez-Gay Mantecon, Miguel Angel, Alonso, Ricardo Blanco, Martinez, Alfonso Corrales, Cervera, Ricard, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Angeles Aguirre-Zamorano, Ma, Carmen Castro-Villegas, Ma, Jimenez Gomez, Yolanda, Ortego, Norberto, Fernandez Roldan, Maria Concepcion, Raya, Enrique, Moleon, Inmaculada Jimenez, de Ramon, Enrique, Quintero, Isabel Diaz, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Dulic, Sonja, Kadar, Gabriella, Hiepe, Falk, Gerl, Velia, Thiel, Silvia, Maresca, Manuel Rodriguez, Lopez-Berrio, Antonio, Aguilar-Quesada, Rocio, Navarro-Linares, Hector, Ioannou, Yiannis, Chamberlain, Chris, Marovac, Jacqueline, Alarcon Riquelme, Marta, Gomes Anjos, Tania, Maranon, Concepcion, Le Lann, Lucas, Simon, Quentin, Rouviere, Benedicte, Varela, Nieves, Muchmore, Brian, Dufour, Aleksandra, Alvarez, Montserrat, Cremer, Jonathan, Lopez-Pedrera, Chary, Ger, Velia, Khodadadi, Laleh, Cheng, Qingyu, De Groof, Aurelie, Trombetta, Elena, Li, Tianlu, Alvarez-Errico, Damiana, Kniesch, Katja, Azevedo, Nancy, Rao, Sambasiva, Jouve, Pierre-Emmanuel, Soret, Perrine, Le Dantec, Christelle, Desvaux, Emiko, Foulquier, Nathan, Chassagnol, Bastien, Hubert, Sandra, Jamin, Christophe, Barturen, Guillermo, Desachy, Guillaume, Devauchelle-Pensec, Valerie, Boudjeniba, Cheiema, Cornec, Divi, Saraux, Alain, Jousse-Joulin, Sandrine, Barbarroja, Nuria, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Beretta, Lorenzo, Chizzolini, Carlo, Kovacs, Laszlo, Witte, Torsten, Bettacchioli, Eleonore, Buttgereit, Anne, Makowska, Zuzanna, Lesche, Ralf, Orietta Borghi, Maria, Martin, Javier, Courtade-Gaiani, Sophie, Xuereb, Laura, Guedj, Mickael, Moingeon, Philippe, Alarcon-Riquelme, Marta E., Laigle, Laurence, Pers, Jacques-Olivier, Vigone, Barbara, Lauwerys, Bernard, Ducreux, Julie, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Neves, Esmeralda, Faria, Raquel, Brandao, Mariana, Campar, Ana, Marinho, Antonio, Farinha, Fatima, Almeida, Isabel, Gonzalez-Gay Mantecon, Miguel Angel, Alonso, Ricardo Blanco, Martinez, Alfonso Corrales, Cervera, Ricard, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Angeles Aguirre-Zamorano, Ma, Carmen Castro-Villegas, Ma, Jimenez Gomez, Yolanda, Ortego, Norberto, Fernandez Roldan, Maria Concepcion, Raya, Enrique, Moleon, Inmaculada Jimenez, de Ramon, Enrique, Quintero, Isabel Diaz, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Dulic, Sonja, Kadar, Gabriella, Hiepe, Falk, Gerl, Velia, Thiel, Silvia, Maresca, Manuel Rodriguez, Lopez-Berrio, Antonio, Aguilar-Quesada, Rocio, Navarro-Linares, Hector, Ioannou, Yiannis, Chamberlain, Chris, Marovac, Jacqueline, Alarcon Riquelme, Marta, Gomes Anjos, Tania, Maranon, Concepcion, Le Lann, Lucas, Simon, Quentin, Rouviere, Benedicte, Varela, Nieves, Muchmore, Brian, Dufour, Aleksandra, Alvarez, Montserrat, Cremer, Jonathan, Lopez-Pedrera, Chary, Ger, Velia, Khodadadi, Laleh, Cheng, Qingyu, De Groof, Aurelie, Trombetta, Elena, Li, Tianlu, Alvarez-Errico, Damiana, Kniesch, Katja, Azevedo, Nancy, Rao, Sambasiva, and Jouve, Pierre-Emmanuel
Abstract: There is currently no approved treatment for primary Sjogren's syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjogren's syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials. Sjogren's syndrome, a disease that primarily affects women, is poorly understood. Here, the authors combine data from a large cohort of patients and healthy controls to identify biomarkers that distinguish patient subgroups to improve our understanding of the disease and facilitate drug development.
Published: 2021

10. 2021 DORIS definition of remission in SLE:Final recommendations from an international task force

Author: van Vollenhoven, Ronald F., Bertsias, George, Doria, Andrea, Isenberg, David, Morand, Eric, Petri, Michelle A., Pons-Estel, Bernardo A., Rahman, Anisur, Ugarte-Gil, Manuel Francisco, Voskuyl, Alexandre, Arnaud, Laurent, Bruce, Ian N., Cervera, Ricard, Costedoat-Chalumeau, Nathalie, Gordon, Caroline, Houssiau, Frédéric A., Mosca, Marta, Schneider, Matthias, Ward, Michael M., Alarcon, Graciela, Aringer, Martin, Askenase, Anka, Bae, Sang Cheol, Bootsma, Hendrika, Boumpas, Dimitrios T., Brunner, Hermine, Clarke, Ann Elaine, Coney, Cindy, Czirják, László, Dörner, Thomas, Faria, Raquel, Fischer, Rebecca, Fritsch-Stork, Ruth, Inanc, Murat, Jacobsen, Søren, Jayne, David, Kuhn, Annegret, van Leeuw, Bernadette, Limper, Maarten, Mariette, Xavier, Navarra, Sandra, Nikpour, Mandana, Olesinska, Marzena Helena, Pons-Estel, Guillermo, Romero-Diaz, Juanita, Rubio, Blanca, Schoenfeld, Yehuda, Bonfá, Eloisa, Smolen, Josef, Teng, Y. K.Onno, Tincani, Angela, Tsang-A-Sjoe, Michel, Vasconcelos, Carlos, Voss, Anne, Werth, Victoria P., Zakharhova, Elena, Aranow, Cynthia, van Vollenhoven, Ronald F., Bertsias, George, Doria, Andrea, Isenberg, David, Morand, Eric, Petri, Michelle A., Pons-Estel, Bernardo A., Rahman, Anisur, Ugarte-Gil, Manuel Francisco, Voskuyl, Alexandre, Arnaud, Laurent, Bruce, Ian N., Cervera, Ricard, Costedoat-Chalumeau, Nathalie, Gordon, Caroline, Houssiau, Frédéric A., Mosca, Marta, Schneider, Matthias, Ward, Michael M., Alarcon, Graciela, Aringer, Martin, Askenase, Anka, Bae, Sang Cheol, Bootsma, Hendrika, Boumpas, Dimitrios T., Brunner, Hermine, Clarke, Ann Elaine, Coney, Cindy, Czirják, László, Dörner, Thomas, Faria, Raquel, Fischer, Rebecca, Fritsch-Stork, Ruth, Inanc, Murat, Jacobsen, Søren, Jayne, David, Kuhn, Annegret, van Leeuw, Bernadette, Limper, Maarten, Mariette, Xavier, Navarra, Sandra, Nikpour, Mandana, Olesinska, Marzena Helena, Pons-Estel, Guillermo, Romero-Diaz, Juanita, Rubio, Blanca, Schoenfeld, Yehuda, Bonfá, Eloisa, Smolen, Josef, Teng, Y. K.Onno, Tincani, Angela, Tsang-A-Sjoe, Michel, Vasconcelos, Carlos, Voss, Anne, Werth, Victoria P., Zakharhova, Elena, and Aranow, Cynthia
Abstract: Objective To achieve consensus on a definition of remission in SLE (DORIS). Background Remission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a framework for such a definition, without reaching a final recommendation. Methods Several systematic literature reviews were performed and specific research questions examined in suitably chosen data sets. The findings were discussed, reformulated as recommendations and voted on. Results Based on data from the literature and several SLE-specific data sets, a set of recommendations was endorsed. Ultimately, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical systemic lupus erythematosus disease activitiy index (SLEDAI)=0, Evaluator’s Global Assessment <0.5 (0–3), prednisolone 5 mg/day or less, and stable antimalarials, immunosuppressives, and biologics. Conclusion The 2021 DORIS definition of remission in SLE is recommended for use in clinical care, education, and research including clinical trials and observational studies.
Published: 2021

11. 2021 DORIS definition of remission in SLE:Final recommendations from an international task force

Author: van Vollenhoven, Ronald F., Bertsias, George, Doria, Andrea, Isenberg, David, Morand, Eric, Petri, Michelle A., Pons-Estel, Bernardo A., Rahman, Anisur, Ugarte-Gil, Manuel Francisco, Voskuyl, Alexandre, Arnaud, Laurent, Bruce, Ian N., Cervera, Ricard, Costedoat-Chalumeau, Nathalie, Gordon, Caroline, Houssiau, Frédéric A., Mosca, Marta, Schneider, Matthias, Ward, Michael M., Alarcon, Graciela, Aringer, Martin, Askenase, Anka, Bae, Sang Cheol, Bootsma, Hendrika, Boumpas, Dimitrios T., Brunner, Hermine, Clarke, Ann Elaine, Coney, Cindy, Czirják, László, Dörner, Thomas, Faria, Raquel, Fischer, Rebecca, Fritsch-Stork, Ruth, Inanc, Murat, Jacobsen, Søren, Jayne, David, Kuhn, Annegret, van Leeuw, Bernadette, Limper, Maarten, Mariette, Xavier, Navarra, Sandra, Nikpour, Mandana, Olesinska, Marzena Helena, Pons-Estel, Guillermo, Romero-Diaz, Juanita, Rubio, Blanca, Schoenfeld, Yehuda, Bonfá, Eloisa, Smolen, Josef, Teng, Y. K.Onno, Tincani, Angela, Tsang-A-Sjoe, Michel, Vasconcelos, Carlos, Voss, Anne, Werth, Victoria P., Zakharhova, Elena, Aranow, Cynthia, van Vollenhoven, Ronald F., Bertsias, George, Doria, Andrea, Isenberg, David, Morand, Eric, Petri, Michelle A., Pons-Estel, Bernardo A., Rahman, Anisur, Ugarte-Gil, Manuel Francisco, Voskuyl, Alexandre, Arnaud, Laurent, Bruce, Ian N., Cervera, Ricard, Costedoat-Chalumeau, Nathalie, Gordon, Caroline, Houssiau, Frédéric A., Mosca, Marta, Schneider, Matthias, Ward, Michael M., Alarcon, Graciela, Aringer, Martin, Askenase, Anka, Bae, Sang Cheol, Bootsma, Hendrika, Boumpas, Dimitrios T., Brunner, Hermine, Clarke, Ann Elaine, Coney, Cindy, Czirják, László, Dörner, Thomas, Faria, Raquel, Fischer, Rebecca, Fritsch-Stork, Ruth, Inanc, Murat, Jacobsen, Søren, Jayne, David, Kuhn, Annegret, van Leeuw, Bernadette, Limper, Maarten, Mariette, Xavier, Navarra, Sandra, Nikpour, Mandana, Olesinska, Marzena Helena, Pons-Estel, Guillermo, Romero-Diaz, Juanita, Rubio, Blanca, Schoenfeld, Yehuda, Bonfá, Eloisa, Smolen, Josef, Teng, Y. K.Onno, Tincani, Angela, Tsang-A-Sjoe, Michel, Vasconcelos, Carlos, Voss, Anne, Werth, Victoria P., Zakharhova, Elena, and Aranow, Cynthia
Abstract: Objective To achieve consensus on a definition of remission in SLE (DORIS). Background Remission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a framework for such a definition, without reaching a final recommendation. Methods Several systematic literature reviews were performed and specific research questions examined in suitably chosen data sets. The findings were discussed, reformulated as recommendations and voted on. Results Based on data from the literature and several SLE-specific data sets, a set of recommendations was endorsed. Ultimately, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical systemic lupus erythematosus disease activitiy index (SLEDAI)=0, Evaluator’s Global Assessment <0.5 (0–3), prednisolone 5 mg/day or less, and stable antimalarials, immunosuppressives, and biologics. Conclusion The 2021 DORIS definition of remission in SLE is recommended for use in clinical care, education, and research including clinical trials and observational studies.
Published: 2021

12. On the Possibility to Use Oxytocin as A Potential Therapeutic Approach for Memory-Related Psychological Disorders

Author: Zarei, Shahab A., Tomaz, Carlos, Vasconcelos, Carlos, Tavares, Maria Clotilde H., Sarani, Melika, Zarei, Shahab A., Tomaz, Carlos, Vasconcelos, Carlos, Tavares, Maria Clotilde H., and Sarani, Melika
Abstract: Studies have indicated that oxytocin has an influence on cognitive functions such as attention, memory and emotional regulation, particularly in the context of social and communicative behavior. There is a growing interest in the use of oxytocin as a treatment for memory-related psychological disorders and social cognitive disorders. The ease of access to the brain intranasally, numerous positive evidences and widely advertised as a wonder drug, foster this interest. However, recent studies also have shown that the effect of oxytocin could varied, even leading to reverse results. The factors that lead to the effects of oxytocin and its underlying processes on such variables are still uncertain. The inconsistent evidence of general oxytocin effects on memory and neuropsychological conditions is an important issue in considering oxytocin as an adjunct therapy. Therefore, understanding the effects of oxytocin, within various emotional and social context, is important before oxytocin could be efficiently used for improving learning and communication impairment or managing neuropsychological disorders. Here, we intend to review various theories regarding the effect of oxytocin on memory, accompanied by its mechanisms which are proposed in human and animal experiments. Based on evidence from these studies, we explore the potentials and limitations of oxytocin’s pharmacotherapeutic applications as a treatment to improve neuropsychological disorders.
Published: 2020

13. On the Possibility to Use Oxytocin as A Potential Therapeutic Approach for Memory-Related Psychological Disorders

Author: Zarei, Shahab A., Tomaz, Carlos, Vasconcelos, Carlos, Tavares, Maria Clotilde H., Sarani, Melika, Zarei, Shahab A., Tomaz, Carlos, Vasconcelos, Carlos, Tavares, Maria Clotilde H., and Sarani, Melika
Abstract: Studies have indicated that oxytocin has an influence on cognitive functions such as attention, memory and emotional regulation, particularly in the context of social and communicative behavior. There is a growing interest in the use of oxytocin as a treatment for memory-related psychological disorders and social cognitive disorders. The ease of access to the brain intranasally, numerous positive evidences and widely advertised as a wonder drug, foster this interest. However, recent studies also have shown that the effect of oxytocin could varied, even leading to reverse results. The factors that lead to the effects of oxytocin and its underlying processes on such variables are still uncertain. The inconsistent evidence of general oxytocin effects on memory and neuropsychological conditions is an important issue in considering oxytocin as an adjunct therapy. Therefore, understanding the effects of oxytocin, within various emotional and social context, is important before oxytocin could be efficiently used for improving learning and communication impairment or managing neuropsychological disorders. Here, we intend to review various theories regarding the effect of oxytocin on memory, accompanied by its mechanisms which are proposed in human and animal experiments. Based on evidence from these studies, we explore the potentials and limitations of oxytocin’s pharmacotherapeutic applications as a treatment to improve neuropsychological disorders.
Published: 2020

14. On the Possibility to Use Oxytocin as A Potential Therapeutic Approach for Memory-Related Psychological Disorders

Author: Zarei, Shahab A., Tomaz, Carlos, Vasconcelos, Carlos, Tavares, Maria Clotilde H., Sarani, Melika, Zarei, Shahab A., Tomaz, Carlos, Vasconcelos, Carlos, Tavares, Maria Clotilde H., and Sarani, Melika
Abstract: Studies have indicated that oxytocin has an influence on cognitive functions such as attention, memory and emotional regulation, particularly in the context of social and communicative behavior. There is a growing interest in the use of oxytocin as a treatment for memory-related psychological disorders and social cognitive disorders. The ease of access to the brain intranasally, numerous positive evidences and widely advertised as a wonder drug, foster this interest. However, recent studies also have shown that the effect of oxytocin could varied, even leading to reverse results. The factors that lead to the effects of oxytocin and its underlying processes on such variables are still uncertain. The inconsistent evidence of general oxytocin effects on memory and neuropsychological conditions is an important issue in considering oxytocin as an adjunct therapy. Therefore, understanding the effects of oxytocin, within various emotional and social context, is important before oxytocin could be efficiently used for improving learning and communication impairment or managing neuropsychological disorders. Here, we intend to review various theories regarding the effect of oxytocin on memory, accompanied by its mechanisms which are proposed in human and animal experiments. Based on evidence from these studies, we explore the potentials and limitations of oxytocin’s pharmacotherapeutic applications as a treatment to improve neuropsychological disorders.
Published: 2020

15. On the Possibility to Use Oxytocin as A Potential Therapeutic Approach for Memory-Related Psychological Disorders

Author: Zarei, Shahab A., Tomaz, Carlos, Vasconcelos, Carlos, Tavares, Maria Clotilde H., Sarani, Melika, Zarei, Shahab A., Tomaz, Carlos, Vasconcelos, Carlos, Tavares, Maria Clotilde H., and Sarani, Melika
Abstract: Studies have indicated that oxytocin has an influence on cognitive functions such as attention, memory and emotional regulation, particularly in the context of social and communicative behavior. There is a growing interest in the use of oxytocin as a treatment for memory-related psychological disorders and social cognitive disorders. The ease of access to the brain intranasally, numerous positive evidences and widely advertised as a wonder drug, foster this interest. However, recent studies also have shown that the effect of oxytocin could varied, even leading to reverse results. The factors that lead to the effects of oxytocin and its underlying processes on such variables are still uncertain. The inconsistent evidence of general oxytocin effects on memory and neuropsychological conditions is an important issue in considering oxytocin as an adjunct therapy. Therefore, understanding the effects of oxytocin, within various emotional and social context, is important before oxytocin could be efficiently used for improving learning and communication impairment or managing neuropsychological disorders. Here, we intend to review various theories regarding the effect of oxytocin on memory, accompanied by its mechanisms which are proposed in human and animal experiments. Based on evidence from these studies, we explore the potentials and limitations of oxytocin’s pharmacotherapeutic applications as a treatment to improve neuropsychological disorders.
Published: 2020

16. Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes and ethnicities

Author: Johnson, Sindhu R., Brinks, Ralph, Costenbader, Karen H., Daikh, David, Mosca, Marta, Ramsey-Goldman, Rosalind, Smolen, Josef S., Wofsy, David, Boumpas, Dimitrios T., Kamen, Diane L., Jayne, David, Cervera, R., Costedoat-Chalumeau, Nathalie, Diamond, Betty, Gladman, Dafna D., Hahn, Bevra, Hiepe, Falk, Jacobsen, Søren, Khanna, Dinesh, Lerstrøm, Kirsten, Massarotti, Elena, McCune, Joseph, Ruiz-Irastorza, Guillermo, Sanchez-Guerrero, Jorge, Schneider, Matthias, Urowitz, Murray, Bertsias, George, Hoyer, Bimba F., Leuchten, Nicolai, Tani, Chiara, Tedeschi, Sara K., Touma, Zahi, Schmajuk, Gabriela, Anic, Branimir, Assan, Florence, Chan, Tak Mao, Clarke, Ann Elaine, Crow, Mary K., Czirják, László, Doria, Andrea, Graninger, Winfried B., Halda-Kiss, Bernadett, Hasni, Sarfaraz, Izmirly, Peter M., Jung, Michelle, Kumánovics, Gábor, Mariette, Xavier, Padjen, Ivan, Pego-Reigosa, José M., Romero-Diaz, Juanita, Rúa-Figueroa, Íñigo, Seror, Raphaèle, Stummvoll, Georg H., Tanaka, Yoshiya, Tektonidou, Maria G., Vasconcelos, Carlos, Vital, Edward M., Wallace, D. J., Yavuz, Sule, Meroni, Pier Luigi, Fritzler, Marvin J., Naden, Ray, Dörner, Thomas, Aringer, Martin, Johnson, Sindhu R., Brinks, Ralph, Costenbader, Karen H., Daikh, David, Mosca, Marta, Ramsey-Goldman, Rosalind, Smolen, Josef S., Wofsy, David, Boumpas, Dimitrios T., Kamen, Diane L., Jayne, David, Cervera, R., Costedoat-Chalumeau, Nathalie, Diamond, Betty, Gladman, Dafna D., Hahn, Bevra, Hiepe, Falk, Jacobsen, Søren, Khanna, Dinesh, Lerstrøm, Kirsten, Massarotti, Elena, McCune, Joseph, Ruiz-Irastorza, Guillermo, Sanchez-Guerrero, Jorge, Schneider, Matthias, Urowitz, Murray, Bertsias, George, Hoyer, Bimba F., Leuchten, Nicolai, Tani, Chiara, Tedeschi, Sara K., Touma, Zahi, Schmajuk, Gabriela, Anic, Branimir, Assan, Florence, Chan, Tak Mao, Clarke, Ann Elaine, Crow, Mary K., Czirják, László, Doria, Andrea, Graninger, Winfried B., Halda-Kiss, Bernadett, Hasni, Sarfaraz, Izmirly, Peter M., Jung, Michelle, Kumánovics, Gábor, Mariette, Xavier, Padjen, Ivan, Pego-Reigosa, José M., Romero-Diaz, Juanita, Rúa-Figueroa, Íñigo, Seror, Raphaèle, Stummvoll, Georg H., Tanaka, Yoshiya, Tektonidou, Maria G., Vasconcelos, Carlos, Vital, Edward M., Wallace, D. J., Yavuz, Sule, Meroni, Pier Luigi, Fritzler, Marvin J., Naden, Ray, Dörner, Thomas, and Aringer, Martin
Abstract: Objectives The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. Methods Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. Results The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%). Conclusions The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.
Published: 2020

17. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus.

Author: Aringer, Martin, Aringer, Martin, Costenbader, Karen, Daikh, David, Brinks, Ralph, Mosca, Marta, Ramsey-Goldman, Rosalind, Smolen, Josef S, Wofsy, David, Boumpas, Dimitrios T, Kamen, Diane L, Jayne, David, Cervera, Ricard, Costedoat-Chalumeau, Nathalie, Diamond, Betty, Gladman, Dafna D, Hahn, Bevra, Hiepe, Falk, Jacobsen, Søren, Khanna, Dinesh, Lerstrøm, Kirsten, Massarotti, Elena, McCune, Joseph, Ruiz-Irastorza, Guillermo, Sanchez-Guerrero, Jorge, Schneider, Matthias, Urowitz, Murray, Bertsias, George, Hoyer, Bimba F, Leuchten, Nicolai, Tani, Chiara, Tedeschi, Sara K, Touma, Zahi, Schmajuk, Gabriela, Anic, Branimir, Assan, Florence, Chan, Tak Mao, Clarke, Ann Elaine, Crow, Mary K, Czirják, László, Doria, Andrea, Graninger, Winfried, Halda-Kiss, Bernadett, Hasni, Sarfaraz, Izmirly, Peter M, Jung, Michelle, Kumánovics, Gábor, Mariette, Xavier, Padjen, Ivan, Pego-Reigosa, José M, Romero-Diaz, Juanita, Rúa-Figueroa Fernández, Íñigo, Seror, Raphaèle, Stummvoll, Georg H, Tanaka, Yoshiya, Tektonidou, Maria G, Vasconcelos, Carlos, Vital, Edward M, Wallace, Daniel J, Yavuz, Sule, Meroni, Pier Luigi, Fritzler, Marvin J, Naden, Ray, Dörner, Thomas, Johnson, Sindhu R, Aringer, Martin, Aringer, Martin, Costenbader, Karen, Daikh, David, Brinks, Ralph, Mosca, Marta, Ramsey-Goldman, Rosalind, Smolen, Josef S, Wofsy, David, Boumpas, Dimitrios T, Kamen, Diane L, Jayne, David, Cervera, Ricard, Costedoat-Chalumeau, Nathalie, Diamond, Betty, Gladman, Dafna D, Hahn, Bevra, Hiepe, Falk, Jacobsen, Søren, Khanna, Dinesh, Lerstrøm, Kirsten, Massarotti, Elena, McCune, Joseph, Ruiz-Irastorza, Guillermo, Sanchez-Guerrero, Jorge, Schneider, Matthias, Urowitz, Murray, Bertsias, George, Hoyer, Bimba F, Leuchten, Nicolai, Tani, Chiara, Tedeschi, Sara K, Touma, Zahi, Schmajuk, Gabriela, Anic, Branimir, Assan, Florence, Chan, Tak Mao, Clarke, Ann Elaine, Crow, Mary K, Czirják, László, Doria, Andrea, Graninger, Winfried, Halda-Kiss, Bernadett, Hasni, Sarfaraz, Izmirly, Peter M, Jung, Michelle, Kumánovics, Gábor, Mariette, Xavier, Padjen, Ivan, Pego-Reigosa, José M, Romero-Diaz, Juanita, Rúa-Figueroa Fernández, Íñigo, Seror, Raphaèle, Stummvoll, Georg H, Tanaka, Yoshiya, Tektonidou, Maria G, Vasconcelos, Carlos, Vital, Edward M, Wallace, Daniel J, Yavuz, Sule, Meroni, Pier Luigi, Fritzler, Marvin J, Naden, Ray, Dörner, Thomas, and Johnson, Sindhu R
Abstract: ObjectiveTo develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).MethodsThis international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects.ResultsThe 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria.ConclusionThese new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.
Published: 2019

18. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus

Author: Aringer, Martin, Costenbader, Karen, Daikh, David, Brinks, Ralph, Mosca, Marta, Ramsey-Goldman, Rosalind, Smolen, Josef S., Wofsy, David, Boumpas, Dimitrios T., Kamen, Diane L., Jayne, David, Cervera, Ricard, Costedoat-Chalumeau, Nathalie, Diamond, Betty, Gladman, Dafna D., Hahn, Bevra, Hiepe, Falk, Jacobsen, Søren, Khanna, Dinesh, Lerstrøm, Kirsten, Massarotti, Elena, McCune, Joseph, Ruiz-Irastorza, Guillermo, Sanchez-Guerrero, Jorge, Schneider, Matthias, Urowitz, Murray, Bertsias, George, Hoyer, Bimba F., Leuchten, Nicolai, Tani, Chiara, Tedeschi, Sara K., Touma, Zahi, Schmajuk, Gabriela, Anic, Branimir, Assan, Florence, Chan, Tak Mao, Clarke, Ann Elaine, Crow, Mary K., Czirják, László, Doria, Andrea, Graninger, Winfried, Halda-Kiss, Bernadett, Hasni, Sarfaraz, Izmirly, Peter M., Jung, Michelle, Kumánovics, Gábor, Mariette, Xavier, Padjen, Ivan, Pego-Reigosa, José M., Romero-Diaz, Juanita, Rúa-Figueroa Fernández, Íñigo, Seror, Raphaèle, Stummvoll, Georg H., Tanaka, Yoshiya, Tektonidou, Maria G., Vasconcelos, Carlos, Vital, Edward M., Wallace, Daniel J., Yavuz, Sule, Meroni, Pier Luigi, Fritzler, Marvin J., Naden, Ray, Dörner, Thomas, Johnson, Sindhu R., Aringer, Martin, Costenbader, Karen, Daikh, David, Brinks, Ralph, Mosca, Marta, Ramsey-Goldman, Rosalind, Smolen, Josef S., Wofsy, David, Boumpas, Dimitrios T., Kamen, Diane L., Jayne, David, Cervera, Ricard, Costedoat-Chalumeau, Nathalie, Diamond, Betty, Gladman, Dafna D., Hahn, Bevra, Hiepe, Falk, Jacobsen, Søren, Khanna, Dinesh, Lerstrøm, Kirsten, Massarotti, Elena, McCune, Joseph, Ruiz-Irastorza, Guillermo, Sanchez-Guerrero, Jorge, Schneider, Matthias, Urowitz, Murray, Bertsias, George, Hoyer, Bimba F., Leuchten, Nicolai, Tani, Chiara, Tedeschi, Sara K., Touma, Zahi, Schmajuk, Gabriela, Anic, Branimir, Assan, Florence, Chan, Tak Mao, Clarke, Ann Elaine, Crow, Mary K., Czirják, László, Doria, Andrea, Graninger, Winfried, Halda-Kiss, Bernadett, Hasni, Sarfaraz, Izmirly, Peter M., Jung, Michelle, Kumánovics, Gábor, Mariette, Xavier, Padjen, Ivan, Pego-Reigosa, José M., Romero-Diaz, Juanita, Rúa-Figueroa Fernández, Íñigo, Seror, Raphaèle, Stummvoll, Georg H., Tanaka, Yoshiya, Tektonidou, Maria G., Vasconcelos, Carlos, Vital, Edward M., Wallace, Daniel J., Yavuz, Sule, Meroni, Pier Luigi, Fritzler, Marvin J., Naden, Ray, Dörner, Thomas, and Johnson, Sindhu R.
Abstract: Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.
Published: 2019

19. Linguagem digital e interativa no ensino da Matemática: entre debates e reflexões

Author: Santos, José Elyton Batista dos, Vasconcelos, Carlos Alberto de, Santos, José Elyton Batista dos, and Vasconcelos, Carlos Alberto de
Abstract: O presente artigo apresenta debates e reflexões acerca da lousa digital interativa (LDI) no ensino e na práxis do professor de Matemática. Nessa perspectiva, foi desenvolvido um panorama dessa interface tecnológica no cenário educacional brasileiro de 2002 a 2017, de acordo com os repositórios do Banco de Teses e Dissertações da Capes e da Biblioteca Digital Brasileira de Teses e Dissertações (BDTD). Assim, a presente pesquisa é do tipo bibliográfico, delimitando-se em um estudo denominado “estado do conhecimento”. Utilizamos como referencial teórico Castells (1999), Belloni (1999) e Fiorentini e Lorenzato (2012). A partir dessa investigação, constatamos que o maior interesse pela temática advém dos programas de mestrado, não apresentando produção alguma com a temática em nível de doutorado, nesse período de quinze anos. Além disso, percebemos que há um maior número de pesquisas centralizadas na Região Sul, fato constatado devido ao investimento, principalmente, do Governo do Estado do Paraná, bem como pelas prefeituras para a incorporação dessa interface tecnológica nas salas de aulas, refletindo gradativamente uma mudança metodológica na construção do saber matemático.
Published: 2018

20. Envolvimento Gastrointestinal na Esclerose Sistémica

Author: Real, André, Lopes, Cristina, Almeida, Isabel, Marinho, António, Vasconcelos, Carlos, Real, André, Lopes, Cristina, Almeida, Isabel, Marinho, António, and Vasconcelos, Carlos
Abstract: Aproximadamente 70 a 90% dos doentes com Esclerose Sistémica apresentam envolvimento gastrointestinal e, em 10% dos casos, este envolvimento constitui a forma de apresentação de Esclerose Sistémica. Todo o trato gastrointestinal pode estar afectado sendo o esófago o órgão mais frequentemente descrito1,2,3,4.
Published: 2018

21. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlöf, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlöf, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
Published: 2017
Full Text: View/download PDF

22. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlof, Jonas Carlsson, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapää Dahlqvist, Solbritt, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlof, Jonas Carlsson, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapää Dahlqvist, Solbritt, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
Published: 2017
Full Text: View/download PDF

23. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlof, Jonas Carlsson, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapää Dahlqvist, Solbritt, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlof, Jonas Carlsson, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapää Dahlqvist, Solbritt, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
Published: 2017
Full Text: View/download PDF

24. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlof, Jonas Carlsson, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapää Dahlqvist, Solbritt, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlof, Jonas Carlsson, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapää Dahlqvist, Solbritt, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
Published: 2017
Full Text: View/download PDF

25. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlöf, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlöf, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
Published: 2017
Full Text: View/download PDF

26. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Cunninghame Graham, Deborah S., Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlof, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapaa Dahlqvist, Solbritt, DAlfonso, Sandra, Martins Da Silva, Berta, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Cunninghame Graham, Deborah S., Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlof, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapaa Dahlqvist, Solbritt, DAlfonso, Sandra, Martins Da Silva, Berta, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P amp;lt; 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE., Funding Agencies|Alliance for Lupus Research; Arthritis Research UK Special Strategic Award [19289]; George Koukis; National Institute for Health Research (NIHR) Biomedical Research Centre based at Guys and St Thomas NHS Foundation Trust; Kings College London; NIH [AR049084]; International Consortium on the Genetics of Systemic Lupus Erythematosus (SLEGEN) [AI083194, CA141700, AR058621]; Proyecto de Excelencia; Consejeria de Andalucia; MUSC [UL1RR029882, 5P60AR062755]; US National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) [K01 AR067280, P60 AR062755, N01AR22265]; APPLE Investigators; NIAMS/NIH [P50-AR055503]; RILITE foundation; Genentech; [AR043814]; [AR-065626]; [AR060366]; [MD007909]; [AI107176]; [AR-057172]; [RC2 AR058959]; [U19 A1082714]; [R01 AR063124]; [P30 GM110766]; [R01 AR056360]; [P60 AR053308]; [R01AR43727]; [NIH AR 043727]; [069572]
Published: 2017
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27. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlöf, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlöf, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
Published: 2017
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28. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Cunninghame Graham, Deborah S., Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlof, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapaa Dahlqvist, Solbritt, DAlfonso, Sandra, Martins Da Silva, Berta, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Cunninghame Graham, Deborah S., Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlof, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapaa Dahlqvist, Solbritt, DAlfonso, Sandra, Martins Da Silva, Berta, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P amp;lt; 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE., Funding Agencies|Alliance for Lupus Research; Arthritis Research UK Special Strategic Award [19289]; George Koukis; National Institute for Health Research (NIHR) Biomedical Research Centre based at Guys and St Thomas NHS Foundation Trust; Kings College London; NIH [AR049084]; International Consortium on the Genetics of Systemic Lupus Erythematosus (SLEGEN) [AI083194, CA141700, AR058621]; Proyecto de Excelencia; Consejeria de Andalucia; MUSC [UL1RR029882, 5P60AR062755]; US National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) [K01 AR067280, P60 AR062755, N01AR22265]; APPLE Investigators; NIAMS/NIH [P50-AR055503]; RILITE foundation; Genentech; [AR043814]; [AR-065626]; [AR060366]; [MD007909]; [AI107176]; [AR-057172]; [RC2 AR058959]; [U19 A1082714]; [R01 AR063124]; [P30 GM110766]; [R01 AR056360]; [P60 AR053308]; [R01AR43727]; [NIH AR 043727]; [069572]
Published: 2017
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29. Transancestral mapping and genetic load in systemic lupus erythematosus.

Author: Langefeld, Carl D, Langefeld, Carl D, Ainsworth, Hannah C, Cunninghame Graham, Deborah S, Kelly, Jennifer A, Comeau, Mary E, Marion, Miranda C, Howard, Timothy D, Ramos, Paula S, Croker, Jennifer A, Morris, David L, Sandling, Johanna K, Almlöf, Jonas Carlsson, Acevedo-Vásquez, Eduardo M, Alarcón, Graciela S, Babini, Alejandra M, Baca, Vicente, Bengtsson, Anders A, Berbotto, Guillermo A, Bijl, Marc, Brown, Elizabeth E, Brunner, Hermine I, Cardiel, Mario H, Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M, Dahlqvist, Solbritt Rantapää, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rúa Figueroa, Iñigo, Doria, Andrea, Edberg, Jeffrey C, Endreffy, Emőke, Esquivel-Valerio, Jorge A, Fortin, Paul R, Freedman, Barry I, Frostegård, Johan, García, Mercedes A, de la Torre, Ignacio García, Gilkeson, Gary S, Gladman, Dafna D, Gunnarsson, Iva, Guthridge, Joel M, Huggins, Jennifer L, James, Judith A, Kallenberg, Cees GM, Kamen, Diane L, Karp, David R, Kaufman, Kenneth M, Kottyan, Leah C, Kovács, László, Laustrup, Helle, Lauwerys, Bernard R, Li, Quan-Zhen, Maradiaga-Ceceña, Marco A, Martín, Javier, McCune, Joseph M, McWilliams, David R, Merrill, Joan T, Miranda, Pedro, Moctezuma, José F, Nath, Swapan K, Niewold, Timothy B, Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A, Pons-Estel, Bernardo A, Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D, Russell, Laurie P, Sabio, José M, Aguilar-Salinas, Carlos A, Scherbarth, Hugo R, Scorza, Raffaella, Seldin, Michael F, Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D, Toloza, Sergio MA, Truedsson, Lennart, Tusié-Luna, Teresa, Vasconcelos, Carlos, Vilá, Luis M, Wallace, Daniel J, Weisman, Michael H, Wither, Joan E, Bhangale, Tushar, Oksenberg, Jorge R, Rioux, John D, Gregersen, Peter K, Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A, Jacob, Chaim O, Sivils, Kathy L, Tsao, Betty P, Schanberg, Laura E, Behrens, Timothy W, Langefeld, Carl D, Langefeld, Carl D, Ainsworth, Hannah C, Cunninghame Graham, Deborah S, Kelly, Jennifer A, Comeau, Mary E, Marion, Miranda C, Howard, Timothy D, Ramos, Paula S, Croker, Jennifer A, Morris, David L, Sandling, Johanna K, Almlöf, Jonas Carlsson, Acevedo-Vásquez, Eduardo M, Alarcón, Graciela S, Babini, Alejandra M, Baca, Vicente, Bengtsson, Anders A, Berbotto, Guillermo A, Bijl, Marc, Brown, Elizabeth E, Brunner, Hermine I, Cardiel, Mario H, Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M, Dahlqvist, Solbritt Rantapää, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rúa Figueroa, Iñigo, Doria, Andrea, Edberg, Jeffrey C, Endreffy, Emőke, Esquivel-Valerio, Jorge A, Fortin, Paul R, Freedman, Barry I, Frostegård, Johan, García, Mercedes A, de la Torre, Ignacio García, Gilkeson, Gary S, Gladman, Dafna D, Gunnarsson, Iva, Guthridge, Joel M, Huggins, Jennifer L, James, Judith A, Kallenberg, Cees GM, Kamen, Diane L, Karp, David R, Kaufman, Kenneth M, Kottyan, Leah C, Kovács, László, Laustrup, Helle, Lauwerys, Bernard R, Li, Quan-Zhen, Maradiaga-Ceceña, Marco A, Martín, Javier, McCune, Joseph M, McWilliams, David R, Merrill, Joan T, Miranda, Pedro, Moctezuma, José F, Nath, Swapan K, Niewold, Timothy B, Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A, Pons-Estel, Bernardo A, Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D, Russell, Laurie P, Sabio, José M, Aguilar-Salinas, Carlos A, Scherbarth, Hugo R, Scorza, Raffaella, Seldin, Michael F, Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D, Toloza, Sergio MA, Truedsson, Lennart, Tusié-Luna, Teresa, Vasconcelos, Carlos, Vilá, Luis M, Wallace, Daniel J, Weisman, Michael H, Wither, Joan E, Bhangale, Tushar, Oksenberg, Jorge R, Rioux, John D, Gregersen, Peter K, Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A, Jacob, Chaim O, Sivils, Kathy L, Tsao, Betty P, Schanberg, Laura E, and Behrens, Timothy W
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10-8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
Published: 2017

30. A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS).

Author: UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, van Vollenhoven, Ronald, Voskuyl, Alexandre, Bertsias, George, Aranow, Cynthia, Aringer, Martin, Arnaud, Laurent, Askanase, Anca, Balážová, Petra, Bonfa, Eloisa, Bootsma, Hendrika, Boumpas, Dimitrios, Bruce, Ian, Cervera, Ricard, Clarke, Ann, Coney, Cindy, Costedoat-Chalumeau, Nathalie, Czirják, László, Derksen, Ronald, Doria, Andrea, Dörner, Thomas, Fischer-Betz, Rebecca, Fritsch-Stork, Ruth, Gordon, Caroline, Graninger, Winfried, Györi, Noémi, Houssiau, Frédéric, Isenberg, David, Jacobsen, Soren, Jayne, David, Kuhn, Annegret, Le Guern, Veronique, Lerstrøm, Kirsten, Levy, Roger, Machado-Ribeiro, Francinne, Mariette, Xavier, Missaykeh, Jamil, Morand, Eric, Mosca, Marta, Inanc, Murat, Navarra, Sandra, Neumann, Irmgard, Olesinska, Marzena, Petri, Michelle, Rahman, Anisur, Rekvig, Ole Petter, Rovensky, Jozef, Shoenfeld, Yehuda, Smolen, Josef, Tincani, Angela, Urowitz, Murray, van Leeuw, Bernadette, Vasconcelos, Carlos, Voss, Anne, Werth, Victoria P, Zakharova, Helena, Zoma, Asad, Schneider, Matthias, Ward, Michael, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, van Vollenhoven, Ronald, Voskuyl, Alexandre, Bertsias, George, Aranow, Cynthia, Aringer, Martin, Arnaud, Laurent, Askanase, Anca, Balážová, Petra, Bonfa, Eloisa, Bootsma, Hendrika, Boumpas, Dimitrios, Bruce, Ian, Cervera, Ricard, Clarke, Ann, Coney, Cindy, Costedoat-Chalumeau, Nathalie, Czirják, László, Derksen, Ronald, Doria, Andrea, Dörner, Thomas, Fischer-Betz, Rebecca, Fritsch-Stork, Ruth, Gordon, Caroline, Graninger, Winfried, Györi, Noémi, Houssiau, Frédéric, Isenberg, David, Jacobsen, Soren, Jayne, David, Kuhn, Annegret, Le Guern, Veronique, Lerstrøm, Kirsten, Levy, Roger, Machado-Ribeiro, Francinne, Mariette, Xavier, Missaykeh, Jamil, Morand, Eric, Mosca, Marta, Inanc, Murat, Navarra, Sandra, Neumann, Irmgard, Olesinska, Marzena, Petri, Michelle, Rahman, Anisur, Rekvig, Ole Petter, Rovensky, Jozef, Shoenfeld, Yehuda, Smolen, Josef, Tincani, Angela, Urowitz, Murray, van Leeuw, Bernadette, Vasconcelos, Carlos, Voss, Anne, Werth, Victoria P, Zakharova, Helena, Zoma, Asad, Schneider, Matthias, and Ward, Michael
Abstract: OBJECTIVES: Treat-to-target recommendations have identified 'remission' as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE. METHODS: An international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%. RESULTS: The task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs).2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment.3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics.The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life. CONCLUSIONS: The work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.
Published: 2017

31. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlöf, Jonas Carlsson, Acevedo-Vásquez, Eduardo M., Alarcón, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapää, D’Alfonso, Sandra, Da Silva, Berta Martins, de la Rúa Figueroa, Iñigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emőke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegård, Johan, García, Mercedes A., de la Torre, Ignacio García, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovács, László, Laustrup, Helle, Lauwerys, Bernard, Li, Quan-Zhen, Maradiaga-Ceceña, Marco A., Martín, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, José F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, José M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusié-Luna, Teresa, Vasconcelos, Carlos, Vilá, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlöf, Jonas Carlsson, Acevedo-Vásquez, Eduardo M., Alarcón, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapää, D’Alfonso, Sandra, Da Silva, Berta Martins, de la Rúa Figueroa, Iñigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emőke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegård, Johan, García, Mercedes A., de la Torre, Ignacio García, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovács, László, Laustrup, Helle, Lauwerys, Bernard, Li, Quan-Zhen, Maradiaga-Ceceña, Marco A., Martín, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, José F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, José M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusié-Luna, Teresa, Vasconcelos, Carlos, Vilá, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., and Silverman, Earl D.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10-8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
Published: 2017

32. Transancestral mapping and genetic load in systemic lupus erythematosus.

Author: Langefeld, Carl D, Langefeld, Carl D, Ainsworth, Hannah C, Cunninghame Graham, Deborah S, Kelly, Jennifer A, Comeau, Mary E, Marion, Miranda C, Howard, Timothy D, Ramos, Paula S, Croker, Jennifer A, Morris, David L, Sandling, Johanna K, Almlöf, Jonas Carlsson, Acevedo-Vásquez, Eduardo M, Alarcón, Graciela S, Babini, Alejandra M, Baca, Vicente, Bengtsson, Anders A, Berbotto, Guillermo A, Bijl, Marc, Brown, Elizabeth E, Brunner, Hermine I, Cardiel, Mario H, Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M, Dahlqvist, Solbritt Rantapää, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rúa Figueroa, Iñigo, Doria, Andrea, Edberg, Jeffrey C, Endreffy, Emőke, Esquivel-Valerio, Jorge A, Fortin, Paul R, Freedman, Barry I, Frostegård, Johan, García, Mercedes A, de la Torre, Ignacio García, Gilkeson, Gary S, Gladman, Dafna D, Gunnarsson, Iva, Guthridge, Joel M, Huggins, Jennifer L, James, Judith A, Kallenberg, Cees GM, Kamen, Diane L, Karp, David R, Kaufman, Kenneth M, Kottyan, Leah C, Kovács, László, Laustrup, Helle, Lauwerys, Bernard R, Li, Quan-Zhen, Maradiaga-Ceceña, Marco A, Martín, Javier, McCune, Joseph M, McWilliams, David R, Merrill, Joan T, Miranda, Pedro, Moctezuma, José F, Nath, Swapan K, Niewold, Timothy B, Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A, Pons-Estel, Bernardo A, Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D, Russell, Laurie P, Sabio, José M, Aguilar-Salinas, Carlos A, Scherbarth, Hugo R, Scorza, Raffaella, Seldin, Michael F, Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D, Toloza, Sergio MA, Truedsson, Lennart, Tusié-Luna, Teresa, Vasconcelos, Carlos, Vilá, Luis M, Wallace, Daniel J, Weisman, Michael H, Wither, Joan E, Bhangale, Tushar, Oksenberg, Jorge R, Rioux, John D, Gregersen, Peter K, Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A, Jacob, Chaim O, Sivils, Kathy L, Tsao, Betty P, Schanberg, Laura E, Behrens, Timothy W, Langefeld, Carl D, Langefeld, Carl D, Ainsworth, Hannah C, Cunninghame Graham, Deborah S, Kelly, Jennifer A, Comeau, Mary E, Marion, Miranda C, Howard, Timothy D, Ramos, Paula S, Croker, Jennifer A, Morris, David L, Sandling, Johanna K, Almlöf, Jonas Carlsson, Acevedo-Vásquez, Eduardo M, Alarcón, Graciela S, Babini, Alejandra M, Baca, Vicente, Bengtsson, Anders A, Berbotto, Guillermo A, Bijl, Marc, Brown, Elizabeth E, Brunner, Hermine I, Cardiel, Mario H, Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M, Dahlqvist, Solbritt Rantapää, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rúa Figueroa, Iñigo, Doria, Andrea, Edberg, Jeffrey C, Endreffy, Emőke, Esquivel-Valerio, Jorge A, Fortin, Paul R, Freedman, Barry I, Frostegård, Johan, García, Mercedes A, de la Torre, Ignacio García, Gilkeson, Gary S, Gladman, Dafna D, Gunnarsson, Iva, Guthridge, Joel M, Huggins, Jennifer L, James, Judith A, Kallenberg, Cees GM, Kamen, Diane L, Karp, David R, Kaufman, Kenneth M, Kottyan, Leah C, Kovács, László, Laustrup, Helle, Lauwerys, Bernard R, Li, Quan-Zhen, Maradiaga-Ceceña, Marco A, Martín, Javier, McCune, Joseph M, McWilliams, David R, Merrill, Joan T, Miranda, Pedro, Moctezuma, José F, Nath, Swapan K, Niewold, Timothy B, Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A, Pons-Estel, Bernardo A, Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D, Russell, Laurie P, Sabio, José M, Aguilar-Salinas, Carlos A, Scherbarth, Hugo R, Scorza, Raffaella, Seldin, Michael F, Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D, Toloza, Sergio MA, Truedsson, Lennart, Tusié-Luna, Teresa, Vasconcelos, Carlos, Vilá, Luis M, Wallace, Daniel J, Weisman, Michael H, Wither, Joan E, Bhangale, Tushar, Oksenberg, Jorge R, Rioux, John D, Gregersen, Peter K, Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A, Jacob, Chaim O, Sivils, Kathy L, Tsao, Betty P, Schanberg, Laura E, and Behrens, Timothy W
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10-8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
Published: 2017

33. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Cunninghame Graham, Deborah S., Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlöf, Jonas Carlsson, Acevedo Vásquez, Eduardo M., Alarcón, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho Venegas, Jorge M., Dahlqvist, Solbritt Rantapää, D’Alfonso, Sandra, Da Silva, Berta Martins, De la Rúa Figueroa, Iñigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emőke, Esquivel Valerio, Jorge Antonio, Fortin, Paul R., Freedman, Barry I., Frostegård, Johan, García, Mercedes A., García de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovács, László, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan Zhen, Maradiaga Ceceña, Marco A., Martín, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, José F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, José M., Aguilar Salinas, Carlos Alberto, Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusié Luna, Teresa, Vasconcelos, Carlos, Vilá, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcón Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Cunninghame Graham, Deborah S., Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlöf, Jonas Carlsson, Acevedo Vásquez, Eduardo M., Alarcón, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho Venegas, Jorge M., Dahlqvist, Solbritt Rantapää, D’Alfonso, Sandra, Da Silva, Berta Martins, De la Rúa Figueroa, Iñigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emőke, Esquivel Valerio, Jorge Antonio, Fortin, Paul R., Freedman, Barry I., Frostegård, Johan, García, Mercedes A., García de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovács, László, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan Zhen, Maradiaga Ceceña, Marco A., Martín, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, José F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, José M., Aguilar Salinas, Carlos Alberto, Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusié Luna, Teresa, Vasconcelos, Carlos, Vilá, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcón Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (B50% of these regions have multiple independent associations); these include 24 novel SLE regions (Po5 10 8), reﬁned association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identiﬁes both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE
Published: 2017

34. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlöf, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlöf, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
Published: 2017
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35. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Cunninghame Graham, Deborah S., Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlof, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapaa Dahlqvist, Solbritt, DAlfonso, Sandra, Martins Da Silva, Berta, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Cunninghame Graham, Deborah S., Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlof, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapaa Dahlqvist, Solbritt, DAlfonso, Sandra, Martins Da Silva, Berta, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P amp;lt; 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE., Funding Agencies|Alliance for Lupus Research; Arthritis Research UK Special Strategic Award [19289]; George Koukis; National Institute for Health Research (NIHR) Biomedical Research Centre based at Guys and St Thomas NHS Foundation Trust; Kings College London; NIH [AR049084]; International Consortium on the Genetics of Systemic Lupus Erythematosus (SLEGEN) [AI083194, CA141700, AR058621]; Proyecto de Excelencia; Consejeria de Andalucia; MUSC [UL1RR029882, 5P60AR062755]; US National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) [K01 AR067280, P60 AR062755, N01AR22265]; APPLE Investigators; NIAMS/NIH [P50-AR055503]; RILITE foundation; Genentech; [AR043814]; [AR-065626]; [AR060366]; [MD007909]; [AI107176]; [AR-057172]; [RC2 AR058959]; [U19 A1082714]; [R01 AR063124]; [P30 GM110766]; [R01 AR056360]; [P60 AR053308]; [R01AR43727]; [NIH AR 043727]; [069572]
Published: 2017
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36. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlöf, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlöf, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
Published: 2017
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37. A framework for remission in SLE:consensus findings from a large international task force on definitions of remission in SLE (DORIS)

Author: van Vollenhoven, Ronald, Voskuyl, Alexandre, Bertsias, George, Aranow, Cynthia, Aringer, Martin, Arnaud, Laurent, Askanase, Anca, Balážová, Petra, Bonfa, Eloisa, Bootsma, Hendrika, Boumpas, Dimitrios, Bruce, Ian, Cervera, Ricard, Clarke, Ann, Coney, Cindy, Costedoat-Chalumeau, Nathalie, Czirják, László, Derksen, Ronald, Doria, Andrea, Dörner, Thomas, Fischer-Betz, Rebecca, Fritsch-Stork, Ruth, Gordon, Caroline, Graninger, Winfried, Györi, Noémi, Houssiau, Frédéric, Isenberg, David, Jacobsen, Soren, Jayne, David, Kuhn, Annegret, Le Guern, Veronique, Lerstrøm, Kirsten, Levy, Roger, Machado-Ribeiro, Francinne, Mariette, Xavier, Missaykeh, Jamil, Morand, Eric, Mosca, Marta, Inanc, Murat, Navarra, Sandra, Neumann, Irmgard, Olesinska, Marzena, Petri, Michelle, Rahman, Anisur, Rekvig, Ole Petter, Rovensky, Jozef, Shoenfeld, Yehuda, Smolen, Josef, Tincani, Angela, Urowitz, Murray, van Leeuw, Bernadette, Vasconcelos, Carlos, Voss, Anne, Werth, Victoria P, Zakharova, Helena, Zoma, Asad, Schneider, Matthias, Ward, Michael, van Vollenhoven, Ronald, Voskuyl, Alexandre, Bertsias, George, Aranow, Cynthia, Aringer, Martin, Arnaud, Laurent, Askanase, Anca, Balážová, Petra, Bonfa, Eloisa, Bootsma, Hendrika, Boumpas, Dimitrios, Bruce, Ian, Cervera, Ricard, Clarke, Ann, Coney, Cindy, Costedoat-Chalumeau, Nathalie, Czirják, László, Derksen, Ronald, Doria, Andrea, Dörner, Thomas, Fischer-Betz, Rebecca, Fritsch-Stork, Ruth, Gordon, Caroline, Graninger, Winfried, Györi, Noémi, Houssiau, Frédéric, Isenberg, David, Jacobsen, Soren, Jayne, David, Kuhn, Annegret, Le Guern, Veronique, Lerstrøm, Kirsten, Levy, Roger, Machado-Ribeiro, Francinne, Mariette, Xavier, Missaykeh, Jamil, Morand, Eric, Mosca, Marta, Inanc, Murat, Navarra, Sandra, Neumann, Irmgard, Olesinska, Marzena, Petri, Michelle, Rahman, Anisur, Rekvig, Ole Petter, Rovensky, Jozef, Shoenfeld, Yehuda, Smolen, Josef, Tincani, Angela, Urowitz, Murray, van Leeuw, Bernadette, Vasconcelos, Carlos, Voss, Anne, Werth, Victoria P, Zakharova, Helena, Zoma, Asad, Schneider, Matthias, and Ward, Michael
Abstract: OBJECTIVES: Treat-to-target recommendations have identified 'remission' as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE.METHODS: An international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%.RESULTS: The task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs).2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment.3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics.The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life.CONCLUSIONS: The work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.
Published: 2017

38. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlof, Jonas Carlsson, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapää Dahlqvist, Solbritt, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlof, Jonas Carlsson, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapää Dahlqvist, Solbritt, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
Published: 2017
Full Text: View/download PDF

39. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Cunninghame Graham, Deborah S., Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlof, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapaa Dahlqvist, Solbritt, DAlfonso, Sandra, Martins Da Silva, Berta, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Cunninghame Graham, Deborah S., Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlof, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapaa Dahlqvist, Solbritt, DAlfonso, Sandra, Martins Da Silva, Berta, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P amp;lt; 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE., Funding Agencies|Alliance for Lupus Research; Arthritis Research UK Special Strategic Award [19289]; George Koukis; National Institute for Health Research (NIHR) Biomedical Research Centre based at Guys and St Thomas NHS Foundation Trust; Kings College London; NIH [AR049084]; International Consortium on the Genetics of Systemic Lupus Erythematosus (SLEGEN) [AI083194, CA141700, AR058621]; Proyecto de Excelencia; Consejeria de Andalucia; MUSC [UL1RR029882, 5P60AR062755]; US National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) [K01 AR067280, P60 AR062755, N01AR22265]; APPLE Investigators; NIAMS/NIH [P50-AR055503]; RILITE foundation; Genentech; [AR043814]; [AR-065626]; [AR060366]; [MD007909]; [AI107176]; [AR-057172]; [RC2 AR058959]; [U19 A1082714]; [R01 AR063124]; [P30 GM110766]; [R01 AR056360]; [P60 AR053308]; [R01AR43727]; [NIH AR 043727]; [069572]
Published: 2017
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40. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Cunninghame Graham, Deborah S., Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlof, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapaa Dahlqvist, Solbritt, DAlfonso, Sandra, Martins Da Silva, Berta, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Cunninghame Graham, Deborah S., Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Carlsson Almlof, Jonas, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapaa Dahlqvist, Solbritt, DAlfonso, Sandra, Martins Da Silva, Berta, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P amp;lt; 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE., Funding Agencies|Alliance for Lupus Research; Arthritis Research UK Special Strategic Award [19289]; George Koukis; National Institute for Health Research (NIHR) Biomedical Research Centre based at Guys and St Thomas NHS Foundation Trust; Kings College London; NIH [AR049084]; International Consortium on the Genetics of Systemic Lupus Erythematosus (SLEGEN) [AI083194, CA141700, AR058621]; Proyecto de Excelencia; Consejeria de Andalucia; MUSC [UL1RR029882, 5P60AR062755]; US National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) [K01 AR067280, P60 AR062755, N01AR22265]; APPLE Investigators; NIAMS/NIH [P50-AR055503]; RILITE foundation; Genentech; [AR043814]; [AR-065626]; [AR060366]; [MD007909]; [AI107176]; [AR-057172]; [RC2 AR058959]; [U19 A1082714]; [R01 AR063124]; [P30 GM110766]; [R01 AR056360]; [P60 AR053308]; [R01AR43727]; [NIH AR 043727]; [069572]
Published: 2017
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41. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Cunninghame Graham, Deborah S., Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlöf, Jonas Carlsson, Acevedo Vásquez, Eduardo M., Alarcón, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho Venegas, Jorge M., Dahlqvist, Solbritt Rantapää, D’Alfonso, Sandra, Da Silva, Berta Martins, De la Rúa Figueroa, Iñigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emőke, Esquivel Valerio, Jorge Antonio, Fortin, Paul R., Freedman, Barry I., Frostegård, Johan, García, Mercedes A., García de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovács, László, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan Zhen, Maradiaga Ceceña, Marco A., Martín, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, José F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, José M., Aguilar Salinas, Carlos Alberto, Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusié Luna, Teresa, Vasconcelos, Carlos, Vilá, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcón Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Cunninghame Graham, Deborah S., Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlöf, Jonas Carlsson, Acevedo Vásquez, Eduardo M., Alarcón, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho Venegas, Jorge M., Dahlqvist, Solbritt Rantapää, D’Alfonso, Sandra, Da Silva, Berta Martins, De la Rúa Figueroa, Iñigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emőke, Esquivel Valerio, Jorge Antonio, Fortin, Paul R., Freedman, Barry I., Frostegård, Johan, García, Mercedes A., García de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovács, László, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan Zhen, Maradiaga Ceceña, Marco A., Martín, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, José F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, José M., Aguilar Salinas, Carlos Alberto, Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusié Luna, Teresa, Vasconcelos, Carlos, Vilá, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvänen, Ann Christine, Rönnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcón Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (B50% of these regions have multiple independent associations); these include 24 novel SLE regions (Po5 10 8), reﬁned association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identiﬁes both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE
Published: 2017

42. Transancestral mapping and genetic load in systemic lupus erythematosus

Author: Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlof, Jonas Carlsson, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapää Dahlqvist, Solbritt, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., Vyse, Timothy J., Langefeld, Carl D., Ainsworth, Hannah C., Graham, Deborah S. Cunninghame, Kelly, Jennifer A., Comeau, Mary E., Marion, Miranda C., Howard, Timothy D., Ramos, Paula S., Croker, Jennifer A., Morris, David L., Sandling, Johanna K., Almlof, Jonas Carlsson, Acevedo-Vasquez, Eduardo M., Alarcon, Graciela S., Babini, Alejandra M., Baca, Vicente, Bengtsson, Anders A., Berbotto, Guillermo A., Bijl, Marc, Brown, Elizabeth E., Brunner, Hermine I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Rantapää Dahlqvist, Solbritt, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegard, Johan, Garcia, Mercedes A., Garcia de la Torre, Ignacio, Gilkeson, Gary S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, Diane L., Karp, David R., Kaufman, Kenneth M., Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martin, Javier, McCune, Joseph M., McWilliams, David R., Merrill, Joan T., Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, Jose M., Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, Carlos, Vila, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcon-Riquelme, Marta E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, Patrick M., and Vyse, Timothy J.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
Published: 2017
Full Text: View/download PDF

43. The Stimulus Power Consumption as Form: The Impact on the Environment

Author: Vieira, Gabriella de Castro, Vasconcelos, Carlos Frederico Saraiva de, Vieira, Gabriella de Castro, and Vasconcelos, Carlos Frederico Saraiva de
Abstract: This paper discusses the power of the consumer, encouraging consumption and environmental impacts. The overall objective of this article is to analyze how the power has been practiced in post-modern society, with the central axis unbridled consumption and environmental consequences. Therefore, a general approach is held on the importance of the consumer to the market, the legal provisions which protect you, the power of the advertising industry, especially the compulsive consumerism. Subsequently, we analyze the environmental impacts and discusses the responsibility of all stakeholders about conscious consumption and sustainability., O presente trabalho aborda o poder do consumidor, o incentivo ao consumismo e os impactos no meio ambiente. O objetivo geral do artigo é analisar como o poder tem sido praticado na sociedade pós-moderna, tendo por eixo central o consumo desenfreado e os reflexos ambientais. Para tanto, é realizada uma abordagem geral acerca da importância do consumidor para o mercado, os dispositivos legais que lhe tutelam, o poder do setor publicitário, destacando-se o consumismo compulsivo. Posteriormente, analisam-se os impactos ambientais e discute-se a responsabilidade de todos os agentes a respeito do consumo consciente e a sustentabilidade.
Published: 2016

44. Proceedings of the 3rd IPLeiria's International Health Congress: Leiria, Portugal. 6-7 May 2016

Author: Tomás, Catarina Cardoso, Oliveira, Emanuel, Sousa, D., Uba-Chupel, M., Furtado, G., Rocha, C., Teixeira, A., Ferreira, P., Alves, Celeste, Gisin, Stefan, Catarino, Elisabete, Carvalho, Nelma, Coucelo, Tiago, Bonfim, Luís, Silva, Carina, Franco, Débora, González, Jesús Alcoba, Jardim, Helena G., Silva, Rita, Baixinho, Cristina L., Presado, Mª Helena, Marques, Mª Fátima, Cardoso, Mário E., Cunha, Marina, Mendes, Joana, Xavier, Ana, Galhardo, Ana, Couto, Margarida, Frade, João G., Nunes, Carla, Mesquita, João R., Nascimento, Maria S., Gonçalves, Guilherme, Castro, Conceição, Mártires, Alice, Monteiro, Mª João, Rainho, Conceição, Caballero, Francisco P., Monago, Fatima M., Guerrero, Jose T., Monago, Rocio M., Trigo, Africa P., Gutierrez, Milagros L., Milanés, Gemma M., Reina, Mercedes G., Villanueva, Ana G., Piñero, Ana S., Aliseda, Isabel R., Ramirez, Francisco B., Ribeiro, Andrea, Quelhas, Ana, Manso, Conceição, Santos, Rafael B., Jimenez, Nuria R., Nuñez, Cristina G., Gomez, Inmaculada R., Fernandez, Mª Jose L., Marquez, Laura A., Moreno, Ana L., Huertas, Mª Jesus Tena, Seabra, Daniel, Salvador, Mª Céu, Braga, Luciene, Parreira, Pedro, Salgueiro-Oliveira, Anabela, Arreguy-Sena, Cristina, Oliveira, Bibiana F., Henriques, Mª Adriana, Santos, Joana, Lebre, Sara, Marques, Alda, Festas, Clarinda, Rodrigues, Sandra, Lumini, José, Figueiredo, Ana G., Hernandez-Martinez, Francisco J., Campi, Liliana, Quintana-Montesdeoca, Mª Pino, Jimenez-Diaz, Juan F., Rodriguez-De-Vera, Bienvenida C., Parente, Alexandra, Mata, Mª Augusta, Pereira, Ana Mª, Fernandes, Adília, Brás, Manuel, Pinto, Mª Rosário, Basto, Marta L., Rei, Ana C., Mónico, Lisete M., Sousa, Gilberta, Morna, Clementina, Freitas, Otília, Freitas, Gregório, Jardim, Ana, Vasconcelos, Rita, Horta, Lina G., Rosa, Roger S., Kranz, Luís F., Nugem, Rita C., Siqueira, Mariana S., Bordin, Ronaldo, Kniess, Rosiane, Lacerda, Josimari T., Guedes, Joana, Machado, Idalina, Almeida, Sidalina, Zilhão, Adriano, Alves, Helder, Ribeiro, Óscar, Amaral, Ana P., Santos, Ana, Monteiro, Joana, Rocha, Mª Clara, Cruz, Rui, Lourenço, Marina, Antunes, Sandra, Mendonça, Verónica, Andrade, Isabel, Osório, Nádia, Valado, Ana, Caseiro, Armando, Gabriel, António, Martins, Anabela C., Mendes, Fernando, Cabral, Lídia, Ferreira, Manuela, Gonçalves, Amadeu, Luz, Tatiana D., Luz, Leonardo, Martins, Raul, Morgado, Alice, Vale-Dias, Maria L., Porta-Nova, Rui, Fleig, Tânia C., Reuter, Éboni M., Froemming, Miriam B., Guerreiro, Sabrina L., Carvalho, Lisiane L., Guedelha, Daniel, Coelho, P., Pereira, A., Calha, António, Cordeiro, Raul, Gonçalves, Ana, Certo, Ana, Galvão, Ana, Welter, Aline, Pereira, Elayne, Ribeiro, Sandra, Kretzer, Marcia, Jiménez-Díaz, Juan-Fernando, Jiménez-Rodríguez, Carla, Hernández-Martínez, Francisco-José, Rodríguez-De-Vera, Bienvenida-Del-Carmen, Marques-Rodrigues, Alexandre, Coelho, Patrícia, Bernardes, Tiago, Pereira, Alexandre, Sousa, Patrícia, Filho, João G., Nazario, Nazare, Amaral, Odete, Garrido, António, Veiga, Nélio, Pedro, Ana R., Pereira, Carlos, Almeia, António, Fernandes, Helder M., Vasconcelos, Carlos, Sousa, Nelson, Reis, Victor M., Monteiro, M. João, Mendes, Romeu, Pinto, Isabel C., Pires, Tânia, Gama, João, Preto, Vera, Silva, Norberto, Magalhães, Carlos, Martins, Matilde, Duarte, Mafalda, Paúl, Constança, Martín, Ignácio, Pinheiro, Arminda A., Xavier, Sandra, Azevedo, Julieta, Bento, Elisabete, Marques, Cristiana, Marques, Mariana, Macedo, António, Pereira, Ana T., Almeida, José P., Almeida, António, Alves, Josiane, Saavedra, Francisco, Maia, Ana S., Oliveira, Michelle T., Sousa, Anderson R., Ferreira, Paulo P., Lopes, Luci S., Santiago, Eujcely C., Monteiro, Sílvia, Jesus, Ângelo, Colaço, Armanda, Carvalho, António, Silva, Rita P., Cruz, Agostinho, Ferreira, Ana, Marques, Catarina, Figueiredo, João P., Paixão, Susana, Lopes, Carla, Moreira, Fernando, Ribeiro, Diana, Fernandes, Telma, Amado, Diogo, Leal, Jéssica, Azevedo, Marcelo, Ramalho, Sónia, Mangas, Catarina, Ribeiro, Jaime, Gonçalves, Rita, Nunes, Amélia F, Tuna, Ana R., Martins, Carlos R., Forte, Henriqueta D., Costa, Cláudia, Tenedório, José A., Santana, Paula, Andrade, J.A., Pinto, J.L., Campofiorito, C., Nunes, S., Carmo, A., Kaliniczenco, A., Alves, B., Mendes, F., Jesus, C., Fonseca, F., Gehrke, F., Albuquerque, Carlos, Batista, Rita, Cunha, Madalena, Madureira, António, Ribeiro, Olivério, Martins, Rosa, Madeira, Teresa, Peixoto-Plácido, Catarina, Santos, Nuno, Santos, Osvaldo, Bergland, Astrid, Bye, Asta, Alarcão, Violeta, Goulão, Beatriz, Mendonça, Nuno, Nicola, Paulo, Clara, João G., Gomes, João, Querido, Ana, Tomás, Catarina, Carvalho, Daniel, Cordeiro, Marina, Rosa, Marlene C., Brandão, Daniela, Araújo, Lia, Minghelli, Beatriz, Richaud, Sylvina, Mendes, Ana L., Marta-Simões, Joana, Trindade, Inês A., Ferreira, Cláudia, Carvalho, Teresa, Pinto-Gouveia, José, Fernandes, Morgana C., Medeiros, Anabela, Pimentel, Rafaela, Fernandes, Andreia, Mendonça, Carlos, Andrade, Susana, Menezes, Ruth L., Bravo, Rafael, Miranda, Marta, Ugartemendia, Lierni, Tena, José Mª, Pérez-Caballero, Francisco L., Fuentes-Broto, Lorena, Rodríguez, Ana B., Carmen, Barriga, Carneiro, M.A., Domingues, J.N., Paixão, S., Figueiredo, J., Nascimento, V.B., Mendes, F, Azzalis, L., Martins, Ana R., Nunes, Amélia, Jorge, Arminda, Amorim, Ana, Silva, André, Martinho, Liliana, Monteiro, Luís, Silva, Rafael, Coelho, Carina, Coelho, Inês, Correia, André, Rodrigues, Diana, Marante, Nídia, Silva, Pedro, Carvalho, Sara, Araujo, André Rts, Ribeiro, Maximiano, Coutinho, Paula, Ventura, Sandra, Roque, Fátima, Calvo, Cristina, Reses, Manoela, Conde, Jorge, Figueiredo, João, Silva, David, Seiça, Luís, Soares, Raquel, Mourão, Ricardo, Kraus, Teresa, Abreu, Ana C., Padilha, José M., Alves, Júlia M., Sousa, Paulino, Oliveira, Manuel, Sousa, Joana, Novais, Sónia, Mendes, Felismina, Pinto, Joana, Cruz, Joana, Duarte, Hugo, Dixe, Maria Dos Anjos, Sousa, Pedro, Cruz, Inês, Bastos, Fernanda, Pereira, Filipe, Carvalho, Francisco L., Oliveira, Teresa T., Raposo, Vítor R., Ribeiro, José C., Barroso, Isabel, Rodrigues, Vítor, Neves, Carmo, Oliveira, Teresa C., Oliveira, Bárbara, Morais, Mª Carminda, Baylina, Pilar, Rodrigues, Rogério, Azeredo, Zaida, Vicente, Corália, Dias, Hélia, Sim-Sim, Margarida, Castilho, Amélia, Melo, Rosa, Graveto, João, Gomes, José, Vaquinhas, Marina, Carvalho, Carla, Mónico, Lisete, Brito, Nuno, Sarroeira, Cassilda, Amendoeira, José, Cunha, Fátima, Cândido, Anabela, Fernandes, Patrícia, Silva, Helena R., Silva, Elsa, Lapa, Leila, Antunes, Cristina, Gomes, Mª José, Escanciano, Susana R., Freitas, Maria, Marôco, João, Fernandes, Ana R., Cabral, Cremilde, Alves, Samuel, Ferreira, António, Príncipe, Fernanda, Seppänen, Ulla-Maija, Ferreira, Margarida, Carvalhais, Maribel, Silva, Marilene, Silva, Joana, Neves, Jéssica, Costa, Diana, Santos, Bruno, Duarte, Soraia, Marques, Sílvia, Mendes, Isabel, Louro, Clarisse, Menino, Eva, Dixe, Maria, Dias, Sara S., Valim, Frederico C., Costa, Joyce O., Bernardes, Lúcia G., Prebianchi, Helena, Rosa, Marlene Cristina, Gonçalves, Narcisa, Martins, Maria M., Kurcgant, Paulina, Vieira, André, Bento, Sandrina, Deodato, Sérgio, Rabiais, Isabel, Reis, Laura, Torres, Ana, Soares, Sérgio, Graça, Pedro, Leitão, Céu, Abreu, Renato, Bellém, Fernando, Almeida, Ana, Ribeiro-Varandas, Edna, Tavares, Ana, Henriques, Carolina, Jordão, Célia, Neco, Sofia, Morais, Carminda, Ferreira, Pedro, Silva, Carla R., Brito, Alice, Silva, Antónia, Postolache, Gabriela, Oliveira, Raul, Moreira, Isabel, Pedro, Luísa, Vicente, Sónia, Domingos, Samuel, Postolache, Octavian, Silva, Darlen, Schneider, Dulcineia, Marques, Fátima M., Pinto, Carlos, Vicente, Sara, Breda, São João, Gomes, José H., Salgueiro, Anabela, Duarte, Nuno, Lopes, José C., Nunes, Hélder, Braga, Luciene M., Araújo, Beatriz, Alves, José M., Sousa, Ana S., Ferrito, Cândida, Ferreira, Pedro L., Rodrigues, Alexandre, Oliveira, Isabel, Martins, Cristina, Macedo, Ana P., Araújo, Odete, Augusto, Cláudia, Braga, Fátima, Gomes, Lisa, Silva, Maria A., Rosário, Rafaela, Pimenta, Luís, Carreira, Diana, Teles, Patrícia, Barros, Teresa, Jácome, Cristina, Capelas, Sylvie, Hall, Andreia, Alves, Dina, Lousada, Marisa, Loureiro, Mª Helena, Camarneiro, Ana, Silva, Margarida, Mendes, Aida, Pedreiro, Ana, G. Silva, Anne, Coelho, Elza S., Melo, Flávio, Ribeiro, Fernando, Torres, Rui, Costa, Rui, Pinho, Tânia, Cruz, Bárbara, Carreiras, Diogo, Ventura, Maria, Cruz, x, Brooks, Dina, Pinto, M Rosário, Lima-Basto, Marta, Neves, Miguel, Bizarro, Carla, Margarida, Couto, Amorim, Ana P., Silva, Eduardo, Cruz, Susana, Valente, Jorge, Guerrero, José T., Gonzalez, Estefania P., Monago, Fátima M., Ugalde, Lierni U., Vélez, Marta M., Tena, Maria J., Becerra, Isabel A., Agudelo, Mª Elizabeth, Acedo, Guadalupe, Bajo, Roberto, Malheiro, Isabel, Gaspar, Filomena, Barros, Luísa, Furtado, Guilherme, Uba-Chupel, Mateus, Rama, Luís, Braga, Margarida, Ferreira, José P., Teixeira, Ana Mª, Cruz, João, Barbosa, Tiago, Simões, Ângela, Coelho, Luís, Martinez-Hernandez, Francisco, Rodriguez-De-Vera, Bienvenida, Rodrigues, Alexandrina, Ramalho, André, Petrica, João, Mendes, Pedro, Serrano, João, Santo, Inês, Rosado, António, Mendonça, Paula, Freitas, Kátia, Ferreira, Dora, Brito, António, Fernandes, Renato, Gomes, Sofia, Pinho, Cláudia, Oliveira, Rita, Oliveira, Ana I., Casimiro, Ana P., Martins, Patrícia, Silva, Iryna, Evangelista, Diana, Leitão, Catarina, Velosa, Fábia, Carecho, Nélio, Dixe, Anjos, Catarino, Helena, Soares, Fátima, Gama, Ester, Gordo, Clementina, Moreira, Eliana, Midões, Cristiana, Santos, Marlene, Machado, Sara, Oliveira, Vânia P., Marques, Rita, Charepe, Zaida, Antunes, Ana, Santos, Sofia, Marques, Silvana F., CaroMinghelli, Eulália, Luís, Mª José, Brandão, Teresa, Marinho, Daniel, Monteiro, Diogo, Paulo, Rui, Monteiro, Lina, Ramalho, Fátima, Santos-Rocha, Rita, Morgado, Sónia, Bento, Teresa, Silva, Isabel, Azevedo, Tatiana, Soares, Salete, Pisco, Jacinta, Olszewer, Efrain O., Oliveira, Sebastião T., Santos, Erica, Maia, Carla, Mendes, Maria F., Oliveira, Rita F., Barreira, Eduarda, Pereira, Ana, Vaz, Josiana A., Novo, André, Silva, Luís D., Maia, Bruno, Ferreira, Eduardo, Pires, Filipa, Andrade, Renato, Camarinha, Luís, César, Ana F., Poço, Mariana, Ventura, David, Loura, Raquel, Gomes, Pedro, Gomes, Catarina, Silva, Cláudia, Melo, Elsa, Lindo, João, Domingos, Joana, Mendes, Zaida, Poeta, Susana, Carvalho, Tiago, Dixe, Mª Anjos, Garcia, Inês, Meneses, Rui, Afonso, Carlos, Faria, Luís, Seixas, Adérito, Granjo, Paulo, Gomes, José C., Souza, Nelba R., Furtado, Guilherme E., Rocha, Saulo V., Silva, Paula, Carvalho, Joana, Morais, Marina Ana, Lebre, Paula, Alencar, Liana, Cardoso, Ilda, Daniel, Fernanda, Luz, Tatiana, Ramos, Maurício R., Medeiros, Dayse C., Carmo, Bruno M., Seabra, André, Padez, Cristina, Silva, Manuel C., Rodrigues, António, Coelho, Alexandre, Caminha, Madson, Matheus, Filipe, Mendes, Elenice, Correia, Jony, Rodriguez-De-Vera, Bienvendida C., Jimenez-Rodriguez, Carla, Armas-Gonzalez, Yadira, Rodrigues, Cátia, Pedroso, Rosa, Apolinário-Hagen, Jennifer, Vehreschild, Viktor, Veloso, Milene, Magalhães, Celina, Cabral, Isabel, Ferraz, Maira, Nave, Filipe, Costa, Emília, Matos, Filomena, Pacheco, José, Dias, António, Duarte, João, Silva, Daniel, Alferes, Valentim R., Brêda, Mª São João, Parreira, Pedro M., Pimenta, Rui, Boavida, José, Silva, Catarina, Ribeiro, Maria, Viega-Branco, Maria, Pereira, Filomena, Almeida, Fabrícia M., Estevez, Gustavo L., Kretzer, Marcia R., João, Paulo V., Nogueira, Paulo, Novais, Sandra, Carneiro, Lara, Mota, Maria, Santiago, Luiz, Fontes-Ribeiro, Carlos, Coutinho, André P., Neto, João S., Vasconcelos, Lélia R., Dantas, Estélio, Dinis, Alexandra, Carvalho, Sérgio, Castilho, Paula, Sarreira-Santos, Alexandra, Figueiredo, Amélia, Medeiros-Garcia, Lurdes, Seabra, Paulo, Rodrigues, Rosa, Fernandes, Paula O., Santiago, Conceição, Figueiredo, Mª Henriqueta, Guimarães, Teresa, Coelho, André, Graça, Anabela, Silva, Ana M., Fonseca, Ana R., Vale-Dias, Luz, Minas, Bárbara, Franco-Borges, Graciete, Simões, Cristina, Serra, Ana, Matos, Maria, Jesus, Luís, Tavares, Ana S., Varandas, Edna, Miranda, Cristiana, Guimarães, Pedro, Gonçalves, Rodrigo, San-Martin, Elisabete A., Goulart, Cássia L., Schneiders, Paloma B., Miranda, Natacha F., Silva, Andrea G., Topa, Joana, Nogueira, Conceição, Neves, Sofia, Ventura, Rita, Nazaré, Cristina, Freitas, Alberto, Mercê, Cristiana, Branco, Marco, Almeida, Pedro, Nascimento, Daniela, Pereira, Juliana, Catela, David, Rafael, Helga, Reis, Alcinda C., Mendes, Ana, Valente, Ana R., Sousa, Diana, Baltazar, Ana L., Oliveira, Ana, Aparício, José, Neves, Joana, Ayoub, Rodrigo, Sousa, Luís, Marques-Vieira, Cristina, Severino, Sandy, José, Helena, Cadorio, Inês, Andrade, Diogo, Domingues, Cátia, Schukg, Susann, Abrantes, Ana M., Gonçalves, Ana C., Sales, Tiago, Teixo, Ricardo, Estrela, Jéssica, Laranjo, Mafalda, Casalta-Lopes, João, Rocha, Clara, Simões, Paulo C., Sarmento-Ribeiro, Ana B., Botelho, Mª Filomena, Rosa, Manuel S., Fonseca, Virgínia, Colaço, Diogo, Neves, Vanessa, Jesus, Carlos, Hesse, Camilla, Svensson, Lola, Siba, Wafa A., Pereira, Cristina, Tomaz, Jorge, Duarte, Diana, Lopes, Nuno V., Fonseca-Pinto, Rui, Brandão, Piedade, Martins, Laura, Cardoso, Margarida, Morais, Nuno, Alves, Nuno, Faria, Paula, Mateus, Artur, Morouço, Pedro, Ferreira, Nelson, Cardoso, Andreia, Lopes, Albino, Soares, Valter, Dias, Tiago, Vardasca, Ricardo, Gabriel, Joaquim, Paredes, Hugo, Reis, Arsénio, Marinho, Sara, Filipe, Vítor, Lains, Jorge, Barroso, João, Da Motta, Carolina, Carvalho, Célia B., Peixoto, Ermelindo, Gomes, Ana A., Costa, Vanessa, Couto, Diana, Marques, Daniel R., Leitão, José A., Tavares, José, Azevedo, Maria H., Silva, Carlos F., Freitas, João, Garcia-Gordillo, Miguel A., Collado-Mateo, Daniel, Chen, Gang, Iezzi, Angelo, Sala, José A., Parraça, José A., Gusi, Narcis, Sousa, Jani, Jardim, Jacinto, Pereira, Anabela, Simões, Sónia, Sardo, Pedro, Guedes, Jenifer, Machado, Paulo, Benevides, Joana, Sousa, Marina, Cabral, Joana, Carvalho, Rosa, Alves, Juliana, Azevedo, Mª Helena, Silva, Carlos, Lee, Huei D., Spolaôr, Newton, Oliva, Jefferson T., Chung, Wu F., Bairros, Keila, Silva, Cláudia D., Souza, Clóvis A., Schroeder, Silvana S., Araújo, Elsa, Monteiro, Helena, Costa, Ricardo, Torgal, Jorge, Henriques, Carolina G., Santos, Luísa, Caceiro, Elisa F., Ramalho, Sónia A., Afreixo, Vera, Santos, João, Mota, Priscilla, Pimentel, Francisco, Caldeira, Suzana N., Ribeiro, Lígia C., Aquino, Priscila S., Ribeiro, Samila G., Pinheiro, Ana B., Lessa, Paula A., Oliveira, Mirna F., Brito, Luísa S., Pinto, Ítalo N., Furtado, Alessandra S., Castro, Régia B., Aquino, Caroline Q., Martins, Eveliny S., Pinheiro, Ana B, Oliveira, Lara L., Pinheiro, Patrícia C., Sousa, Caroline R., Freitas, Vívien A., Silva, Tatiane M., Lima, Adman S., Andrade, Karizia V., Oliveira, Camila A., Vidal, Eglidia F., Ganho-Ávila, Ana, Moura-Ramos, Mariana, Gonçalves, Óscar, Almeida, Jorge, Silva, Armando, Brito, Irma, Amado, João, Rodrigo, António, Gomes, Fernando, Luís, Sara, Cavalheiro, Luís, Gonçalves, Rui, Lopes, Rui S., Fiorin, Bruno H., Santos, Marina S., Oliveira, Edmar S., Moreira, Rita L., Oliveira, Elizabete A., Filho, Braulio L., Palmeira, Lara, Garcia, Teresa, Cardoso, Sara, Oliveira, Sara, Campos, Mariana, Gaudêncio, Iris, Martins, Fernando, Ferreira, Lino, Lopes, Nuno, Marques, Ana R., Carvalho, Rui, Costa, Pablo O., Silva, Maiza M., Alvarenga-Martins, Nathália, Pinto, Paulo F., Oliveira, Denize C., Parreira, Pedro D., Gomes, Antônio T., Lage, Isabel, Cabrita, José, Teixeira, Laetitia, Silva, Sara, Cordeiro, Eugénio, Pimentel, João, Ferro-Lebres, Vera, Souza, Juliana A., Tavares, Mariline, Passadouro, Rui, Peralta, Teresa, Ferreira, Carlos, Lourenço, Georgina, Honório, Samuel, Simões, Alexandra, Carvalho, Lucinda, Figueiredo, Daniela, Valente, Carolina, Ribas, Patrícia, Brandão, Frederico, Sousa, Cesar, Mendes, Francisco, Fernandes, Rosina, Martins, Emília, Magalhães, Cátia, Araújo, Patrícia, Grande, Carla, Vieitez, Juan G., Bianchini, Bruna, Costa, Tânia, Almeida, Armando, Baffour, Gabriel, Laranjeira, Carlos, Guerra, Magda, Barbeiro, Ana P., Ferreira, Regina, Lopes, Sara, Nunes, Liliana, Martins, Julian, Magajewski, Flávio, Soares, Célia, Marques, António, Batista, Marco, Castuera, Ruth J., Mesquita, Helena, Faustino, António, Santos, Jorge, Vizzotto, Betina P., Frigo, Leticia, Pivetta, Hedioneia F., Sardo, Dolores, Abreu, Wilson, Figueiredo, Mª Céu, Jimenez-Castuera, Ruth, Silveira, Paulo, Oliveira, Catarina, Rodriguez, Cláudia K., Kretzer, Márcia R., Nazário, Nazaré O., Cruz, Pedro, Vaz, Daniela C., Ruben, Rui B., Avelelas, Francisco, Silva, Susana, Campos, Mª Jorge, Almeida, Maria, Gonçalves, Liliana, Antunes, Lígia, Simões, João, Cardoso, Susana, Loureiro, Isabel, Santos, Flávia, Alves, Gilberto, Soar, Cláudia, Marsi, Teresa O., Silva, Ernestina, Pedrosa, Dora, Leça, Andrea, Gomes, Maria, Fernandes, Paula, Noné, Ana, Combadão, Jaime, Ramalhete, Cátia, Figueiredo, Paulo, Caeiro, Patrícia, Fontana, Karine C., Machado, Patrícia O., Borges, Raphaelle, Barbosa, Flávio, Sá, Dayse, Brunhoso, Germana, Aparício, Graça, Carvalho, Amâncio, Garcia, Ana P., Santos, Adriana, Brás, Carina, Carvalho, Inês, Batalha, Joana, Glória, Margarida, Bexiga, Filipa, Paraíso, Nilson, Lima, Cristóvão F., Dias, Alberto P., Espada, Mário, Marques, Mário, Veiga-Branco, Mª, Lima, Vera, Cruz, Graça, Barreiros, Luísa, Duarte, Catarina, Lima, Teresa Maneca, Medina, María S., Blanco, Valeriana G., Lopes, Elisa, Virgolino, Ana, Ambrósio, Sara, Almeida, Inês, Marques, Tatiana, Heitor, Mª João, Olivares, Pedro R., Oliveira, Anabela, Cheio, Mónica, Pereira, Olívia R., Pinto, Sara, Oliveira, Adriana, Manso, M. Conceição, Sousa, Carla, Vinha, Ana F., Machado, Mª Manuela, Vieira, Margarida, Fernandes, Beatriz, Tomás, Teresa, Quirino, Diogo, Desouzart, Gustavo, Matos, Rui, Bordini, Magali, Mouroço, Pedro, Matos, Ana R., Serapioni, Mauro, Costa, André, Ribeiro, João, Lobato, João, Martin, Inmaculada Z., Björklund, Anita, Tavares, Aida I., Tavares, Nuno, Valente, João, Ortiga, Angela B., Calvo, Mª Cristina, Natal, Sônia, Pereira, Marta, Prata, Ana R., Nelas, Paula, Carneiro, Juliana, Couto, Cristina, Souza, Géssica M., Almada, Lívia F., Conceição, Milena A., Domingues, Gabriela, Ferreira, Irina, Costa, Ana R., Cardoso, Américo, Meireles, Alexandra, Vieira, Viviane L., Vincha, Kellem R., Cervato-Mancuso, Ana Mª, Faria, Melissa, Reis, Cláudia, Cova, Marco P., Ascenso, Rita T., Almeida, Henrique A., Oliveira, Eunice G., Santana, Miguel, Pereira, Rafael, Jesus, Rita, Tapadas, Rodrigo, Tim-Tim, Carolina, Cezanne, Catarina, Lagoa, Matilde, Lopes, João, Almeida, Henrique, Amado, Sandra, Carrão, Luís, Saboga-Nunes, Luís, Oliveira, Suzete, Escoval, Ana, Assunção, Victor, Luís, Henrique, Luís, Luís, Fotschl, Ulrike, Lirk, Gerald, Silva, Paula A., Ruivo, Joana, Silva, Vânia, Ferraz, Vera, Neves, Joel, Correia, Telma, Amorim, Helena, Pereira, Elsa S., Santos, Leonino S., Reis, Ana S., Rombo, João, Fernandes, Jorge C., Freire, Ana, Francisco, Irene, Louro, Mª Clarisse, Lopes, Saudade, Oliveira, Ana P., Gordo, Sara, Queirós, Paulo, Rodrigues, Teresa, Lobão, Catarina, Moura, Cynthia B., Dreyer, Laysa C., Meneghetti, Vanize, Cabral, Priscila P., Pinto, Francisca, Esteves, Mª Raquel, Galvão, Sofia, Tytgat, Ite, Casas-Novas, Mónica, Bernardo, Helena, Sousa, Gracinda, Sousa, Ana P., Belo, Pedro, Martins, Fátima, Pulido-Fuentes, Montserrat, Cabral, Gil, Prado, Alessandro, Carvalho, Yara M., Campos, Maria, Moreira, Liliana, Ferreira, José, Teixeira, Ana, Tomás, Catarina Cardoso, Oliveira, Emanuel, Sousa, D., Uba-Chupel, M., Furtado, G., Rocha, C., Teixeira, A., Ferreira, P., Alves, Celeste, Gisin, Stefan, Catarino, Elisabete, Carvalho, Nelma, Coucelo, Tiago, Bonfim, Luís, Silva, Carina, Franco, Débora, González, Jesús Alcoba, Jardim, Helena G., Silva, Rita, Baixinho, Cristina L., Presado, Mª Helena, Marques, Mª Fátima, Cardoso, Mário E., Cunha, Marina, Mendes, Joana, Xavier, Ana, Galhardo, Ana, Couto, Margarida, Frade, João G., Nunes, Carla, Mesquita, João R., Nascimento, Maria S., Gonçalves, Guilherme, Castro, Conceição, Mártires, Alice, Monteiro, Mª João, Rainho, Conceição, Caballero, Francisco P., Monago, Fatima M., Guerrero, Jose T., Monago, Rocio M., Trigo, Africa P., Gutierrez, Milagros L., Milanés, Gemma M., Reina, Mercedes G., Villanueva, Ana G., Piñero, Ana S., Aliseda, Isabel R., Ramirez, Francisco B., Ribeiro, Andrea, Quelhas, Ana, Manso, Conceição, Santos, Rafael B., Jimenez, Nuria R., Nuñez, Cristina G., Gomez, Inmaculada R., Fernandez, Mª Jose L., Marquez, Laura A., Moreno, Ana L., Huertas, Mª Jesus Tena, Seabra, Daniel, Salvador, Mª Céu, Braga, Luciene, Parreira, Pedro, Salgueiro-Oliveira, Anabela, Arreguy-Sena, Cristina, Oliveira, Bibiana F., Henriques, Mª Adriana, Santos, Joana, Lebre, Sara, Marques, Alda, Festas, Clarinda, Rodrigues, Sandra, Lumini, José, Figueiredo, Ana G., Hernandez-Martinez, Francisco J., Campi, Liliana, Quintana-Montesdeoca, Mª Pino, Jimenez-Diaz, Juan F., Rodriguez-De-Vera, Bienvenida C., Parente, Alexandra, Mata, Mª Augusta, Pereira, Ana Mª, Fernandes, Adília, Brás, Manuel, Pinto, Mª Rosário, Basto, Marta L., Rei, Ana C., Mónico, Lisete M., Sousa, Gilberta, Morna, Clementina, Freitas, Otília, Freitas, Gregório, Jardim, Ana, Vasconcelos, Rita, Horta, Lina G., Rosa, Roger S., Kranz, Luís F., Nugem, Rita C., Siqueira, Mariana S., Bordin, Ronaldo, Kniess, Rosiane, Lacerda, Josimari T., Guedes, Joana, Machado, Idalina, Almeida, Sidalina, Zilhão, Adriano, Alves, Helder, Ribeiro, Óscar, Amaral, Ana P., Santos, Ana, Monteiro, Joana, Rocha, Mª Clara, Cruz, Rui, Lourenço, Marina, Antunes, Sandra, Mendonça, Verónica, Andrade, Isabel, Osório, Nádia, Valado, Ana, Caseiro, Armando, Gabriel, António, Martins, Anabela C., Mendes, Fernando, Cabral, Lídia, Ferreira, Manuela, Gonçalves, Amadeu, Luz, Tatiana D., Luz, Leonardo, Martins, Raul, Morgado, Alice, Vale-Dias, Maria L., Porta-Nova, Rui, Fleig, Tânia C., Reuter, Éboni M., Froemming, Miriam B., Guerreiro, Sabrina L., Carvalho, Lisiane L., Guedelha, Daniel, Coelho, P., Pereira, A., Calha, António, Cordeiro, Raul, Gonçalves, Ana, Certo, Ana, Galvão, Ana, Welter, Aline, Pereira, Elayne, Ribeiro, Sandra, Kretzer, Marcia, Jiménez-Díaz, Juan-Fernando, Jiménez-Rodríguez, Carla, Hernández-Martínez, Francisco-José, Rodríguez-De-Vera, Bienvenida-Del-Carmen, Marques-Rodrigues, Alexandre, Coelho, Patrícia, Bernardes, Tiago, Pereira, Alexandre, Sousa, Patrícia, Filho, João G., Nazario, Nazare, Amaral, Odete, Garrido, António, Veiga, Nélio, Pedro, Ana R., Pereira, Carlos, Almeia, António, Fernandes, Helder M., Vasconcelos, Carlos, Sousa, Nelson, Reis, Victor M., Monteiro, M. João, Mendes, Romeu, Pinto, Isabel C., Pires, Tânia, Gama, João, Preto, Vera, Silva, Norberto, Magalhães, Carlos, Martins, Matilde, Duarte, Mafalda, Paúl, Constança, Martín, Ignácio, Pinheiro, Arminda A., Xavier, Sandra, Azevedo, Julieta, Bento, Elisabete, Marques, Cristiana, Marques, Mariana, Macedo, António, Pereira, Ana T., Almeida, José P., Almeida, António, Alves, Josiane, Saavedra, Francisco, Maia, Ana S., Oliveira, Michelle T., Sousa, Anderson R., Ferreira, Paulo P., Lopes, Luci S., Santiago, Eujcely C., Monteiro, Sílvia, Jesus, Ângelo, Colaço, Armanda, Carvalho, António, Silva, Rita P., Cruz, Agostinho, Ferreira, Ana, Marques, Catarina, Figueiredo, João P., Paixão, Susana, Lopes, Carla, Moreira, Fernando, Ribeiro, Diana, Fernandes, Telma, Amado, Diogo, Leal, Jéssica, Azevedo, Marcelo, Ramalho, Sónia, Mangas, Catarina, Ribeiro, Jaime, Gonçalves, Rita, Nunes, Amélia F, Tuna, Ana R., Martins, Carlos R., Forte, Henriqueta D., Costa, Cláudia, Tenedório, José A., Santana, Paula, Andrade, J.A., Pinto, J.L., Campofiorito, C., Nunes, S., Carmo, A., Kaliniczenco, A., Alves, B., Mendes, F., Jesus, C., Fonseca, F., Gehrke, F., Albuquerque, Carlos, Batista, Rita, Cunha, Madalena, Madureira, António, Ribeiro, Olivério, Martins, Rosa, Madeira, Teresa, Peixoto-Plácido, Catarina, Santos, Nuno, Santos, Osvaldo, Bergland, Astrid, Bye, Asta, Alarcão, Violeta, Goulão, Beatriz, Mendonça, Nuno, Nicola, Paulo, Clara, João G., Gomes, João, Querido, Ana, Tomás, Catarina, Carvalho, Daniel, Cordeiro, Marina, Rosa, Marlene C., Brandão, Daniela, Araújo, Lia, Minghelli, Beatriz, Richaud, Sylvina, Mendes, Ana L., Marta-Simões, Joana, Trindade, Inês A., Ferreira, Cláudia, Carvalho, Teresa, Pinto-Gouveia, José, Fernandes, Morgana C., Medeiros, Anabela, Pimentel, Rafaela, Fernandes, Andreia, Mendonça, Carlos, Andrade, Susana, Menezes, Ruth L., Bravo, Rafael, Miranda, Marta, Ugartemendia, Lierni, Tena, José Mª, Pérez-Caballero, Francisco L., Fuentes-Broto, Lorena, Rodríguez, Ana B., Carmen, Barriga, Carneiro, M.A., Domingues, J.N., Paixão, S., Figueiredo, J., Nascimento, V.B., Mendes, F, Azzalis, L., Martins, Ana R., Nunes, Amélia, Jorge, Arminda, Amorim, Ana, Silva, André, Martinho, Liliana, Monteiro, Luís, Silva, Rafael, Coelho, Carina, Coelho, Inês, Correia, André, Rodrigues, Diana, Marante, Nídia, Silva, Pedro, Carvalho, Sara, Araujo, André Rts, Ribeiro, Maximiano, Coutinho, Paula, Ventura, Sandra, Roque, Fátima, Calvo, Cristina, Reses, Manoela, Conde, Jorge, Figueiredo, João, Silva, David, Seiça, Luís, Soares, Raquel, Mourão, Ricardo, Kraus, Teresa, Abreu, Ana C., Padilha, José M., Alves, Júlia M., Sousa, Paulino, Oliveira, Manuel, Sousa, Joana, Novais, Sónia, Mendes, Felismina, Pinto, Joana, Cruz, Joana, Duarte, Hugo, Dixe, Maria Dos Anjos, Sousa, Pedro, Cruz, Inês, Bastos, Fernanda, Pereira, Filipe, Carvalho, Francisco L., Oliveira, Teresa T., Raposo, Vítor R., Ribeiro, José C., Barroso, Isabel, Rodrigues, Vítor, Neves, Carmo, Oliveira, Teresa C., Oliveira, Bárbara, Morais, Mª Carminda, Baylina, Pilar, Rodrigues, Rogério, Azeredo, Zaida, Vicente, Corália, Dias, Hélia, Sim-Sim, Margarida, Castilho, Amélia, Melo, Rosa, Graveto, João, Gomes, José, Vaquinhas, Marina, Carvalho, Carla, Mónico, Lisete, Brito, Nuno, Sarroeira, Cassilda, Amendoeira, José, Cunha, Fátima, Cândido, Anabela, Fernandes, Patrícia, Silva, Helena R., Silva, Elsa, Lapa, Leila, Antunes, Cristina, Gomes, Mª José, Escanciano, Susana R., Freitas, Maria, Marôco, João, Fernandes, Ana R., Cabral, Cremilde, Alves, Samuel, Ferreira, António, Príncipe, Fernanda, Seppänen, Ulla-Maija, Ferreira, Margarida, Carvalhais, Maribel, Silva, Marilene, Silva, Joana, Neves, Jéssica, Costa, Diana, Santos, Bruno, Duarte, Soraia, Marques, Sílvia, Mendes, Isabel, Louro, Clarisse, Menino, Eva, Dixe, Maria, Dias, Sara S., Valim, Frederico C., Costa, Joyce O., Bernardes, Lúcia G., Prebianchi, Helena, Rosa, Marlene Cristina, Gonçalves, Narcisa, Martins, Maria M., Kurcgant, Paulina, Vieira, André, Bento, Sandrina, Deodato, Sérgio, Rabiais, Isabel, Reis, Laura, Torres, Ana, Soares, Sérgio, Graça, Pedro, Leitão, Céu, Abreu, Renato, Bellém, Fernando, Almeida, Ana, Ribeiro-Varandas, Edna, Tavares, Ana, Henriques, Carolina, Jordão, Célia, Neco, Sofia, Morais, Carminda, Ferreira, Pedro, Silva, Carla R., Brito, Alice, Silva, Antónia, Postolache, Gabriela, Oliveira, Raul, Moreira, Isabel, Pedro, Luísa, Vicente, Sónia, Domingos, Samuel, Postolache, Octavian, Silva, Darlen, Schneider, Dulcineia, Marques, Fátima M., Pinto, Carlos, Vicente, Sara, Breda, São João, Gomes, José H., Salgueiro, Anabela, Duarte, Nuno, Lopes, José C., Nunes, Hélder, Braga, Luciene M., Araújo, Beatriz, Alves, José M., Sousa, Ana S., Ferrito, Cândida, Ferreira, Pedro L., Rodrigues, Alexandre, Oliveira, Isabel, Martins, Cristina, Macedo, Ana P., Araújo, Odete, Augusto, Cláudia, Braga, Fátima, Gomes, Lisa, Silva, Maria A., Rosário, Rafaela, Pimenta, Luís, Carreira, Diana, Teles, Patrícia, Barros, Teresa, Jácome, Cristina, Capelas, Sylvie, Hall, Andreia, Alves, Dina, Lousada, Marisa, Loureiro, Mª Helena, Camarneiro, Ana, Silva, Margarida, Mendes, Aida, Pedreiro, Ana, G. Silva, Anne, Coelho, Elza S., Melo, Flávio, Ribeiro, Fernando, Torres, Rui, Costa, Rui, Pinho, Tânia, Cruz, Bárbara, Carreiras, Diogo, Ventura, Maria, Cruz, x, Brooks, Dina, Pinto, M Rosário, Lima-Basto, Marta, Neves, Miguel, Bizarro, Carla, Margarida, Couto, Amorim, Ana P., Silva, Eduardo, Cruz, Susana, Valente, Jorge, Guerrero, José T., Gonzalez, Estefania P., Monago, Fátima M., Ugalde, Lierni U., Vélez, Marta M., Tena, Maria J., Becerra, Isabel A., Agudelo, Mª Elizabeth, Acedo, Guadalupe, Bajo, Roberto, Malheiro, Isabel, Gaspar, Filomena, Barros, Luísa, Furtado, Guilherme, Uba-Chupel, Mateus, Rama, Luís, Braga, Margarida, Ferreira, José P., Teixeira, Ana Mª, Cruz, João, Barbosa, Tiago, Simões, Ângela, Coelho, Luís, Martinez-Hernandez, Francisco, Rodriguez-De-Vera, Bienvenida, Rodrigues, Alexandrina, Ramalho, André, Petrica, João, Mendes, Pedro, Serrano, João, Santo, Inês, Rosado, António, Mendonça, Paula, Freitas, Kátia, Ferreira, Dora, Brito, António, Fernandes, Renato, Gomes, Sofia, Pinho, Cláudia, Oliveira, Rita, Oliveira, Ana I., Casimiro, Ana P., Martins, Patrícia, Silva, Iryna, Evangelista, Diana, Leitão, Catarina, Velosa, Fábia, Carecho, Nélio, Dixe, Anjos, Catarino, Helena, Soares, Fátima, Gama, Ester, Gordo, Clementina, Moreira, Eliana, Midões, Cristiana, Santos, Marlene, Machado, Sara, Oliveira, Vânia P., Marques, Rita, Charepe, Zaida, Antunes, Ana, Santos, Sofia, Marques, Silvana F., CaroMinghelli, Eulália, Luís, Mª José, Brandão, Teresa, Marinho, Daniel, Monteiro, Diogo, Paulo, Rui, Monteiro, Lina, Ramalho, Fátima, Santos-Rocha, Rita, Morgado, Sónia, Bento, Teresa, Silva, Isabel, Azevedo, Tatiana, Soares, Salete, Pisco, Jacinta, Olszewer, Efrain O., Oliveira, Sebastião T., Santos, Erica, Maia, Carla, Mendes, Maria F., Oliveira, Rita F., Barreira, Eduarda, Pereira, Ana, Vaz, Josiana A., Novo, André, Silva, Luís D., Maia, Bruno, Ferreira, Eduardo, Pires, Filipa, Andrade, Renato, Camarinha, Luís, César, Ana F., Poço, Mariana, Ventura, David, Loura, Raquel, Gomes, Pedro, Gomes, Catarina, Silva, Cláudia, Melo, Elsa, Lindo, João, Domingos, Joana, Mendes, Zaida, Poeta, Susana, Carvalho, Tiago, Dixe, Mª Anjos, Garcia, Inês, Meneses, Rui, Afonso, Carlos, Faria, Luís, Seixas, Adérito, Granjo, Paulo, Gomes, José C., Souza, Nelba R., Furtado, Guilherme E., Rocha, Saulo V., Silva, Paula, Carvalho, Joana, Morais, Marina Ana, Lebre, Paula, Alencar, Liana, Cardoso, Ilda, Daniel, Fernanda, Luz, Tatiana, Ramos, Maurício R., Medeiros, Dayse C., Carmo, Bruno M., Seabra, André, Padez, Cristina, Silva, Manuel C., Rodrigues, António, Coelho, Alexandre, Caminha, Madson, Matheus, Filipe, Mendes, Elenice, Correia, Jony, Rodriguez-De-Vera, Bienvendida C., Jimenez-Rodriguez, Carla, Armas-Gonzalez, Yadira, Rodrigues, Cátia, Pedroso, Rosa, Apolinário-Hagen, Jennifer, Vehreschild, Viktor, Veloso, Milene, Magalhães, Celina, Cabral, Isabel, Ferraz, Maira, Nave, Filipe, Costa, Emília, Matos, Filomena, Pacheco, José, Dias, António, Duarte, João, Silva, Daniel, Alferes, Valentim R., Brêda, Mª São João, Parreira, Pedro M., Pimenta, Rui, Boavida, José, Silva, Catarina, Ribeiro, Maria, Viega-Branco, Maria, Pereira, Filomena, Almeida, Fabrícia M., Estevez, Gustavo L., Kretzer, Marcia R., João, Paulo V., Nogueira, Paulo, Novais, Sandra, Carneiro, Lara, Mota, Maria, Santiago, Luiz, Fontes-Ribeiro, Carlos, Coutinho, André P., Neto, João S., Vasconcelos, Lélia R., Dantas, Estélio, Dinis, Alexandra, Carvalho, Sérgio, Castilho, Paula, Sarreira-Santos, Alexandra, Figueiredo, Amélia, Medeiros-Garcia, Lurdes, Seabra, Paulo, Rodrigues, Rosa, Fernandes, Paula O., Santiago, Conceição, Figueiredo, Mª Henriqueta, Guimarães, Teresa, Coelho, André, Graça, Anabela, Silva, Ana M., Fonseca, Ana R., Vale-Dias, Luz, Minas, Bárbara, Franco-Borges, Graciete, Simões, Cristina, Serra, Ana, Matos, Maria, Jesus, Luís, Tavares, Ana S., Varandas, Edna, Miranda, Cristiana, Guimarães, Pedro, Gonçalves, Rodrigo, San-Martin, Elisabete A., Goulart, Cássia L., Schneiders, Paloma B., Miranda, Natacha F., Silva, Andrea G., Topa, Joana, Nogueira, Conceição, Neves, Sofia, Ventura, Rita, Nazaré, Cristina, Freitas, Alberto, Mercê, Cristiana, Branco, Marco, Almeida, Pedro, Nascimento, Daniela, Pereira, Juliana, Catela, David, Rafael, Helga, Reis, Alcinda C., Mendes, Ana, Valente, Ana R., Sousa, Diana, Baltazar, Ana L., Oliveira, Ana, Aparício, José, Neves, Joana, Ayoub, Rodrigo, Sousa, Luís, Marques-Vieira, Cristina, Severino, Sandy, José, Helena, Cadorio, Inês, Andrade, Diogo, Domingues, Cátia, Schukg, Susann, Abrantes, Ana M., Gonçalves, Ana C., Sales, Tiago, Teixo, Ricardo, Estrela, Jéssica, Laranjo, Mafalda, Casalta-Lopes, João, Rocha, Clara, Simões, Paulo C., Sarmento-Ribeiro, Ana B., Botelho, Mª Filomena, Rosa, Manuel S., Fonseca, Virgínia, Colaço, Diogo, Neves, Vanessa, Jesus, Carlos, Hesse, Camilla, Svensson, Lola, Siba, Wafa A., Pereira, Cristina, Tomaz, Jorge, Duarte, Diana, Lopes, Nuno V., Fonseca-Pinto, Rui, Brandão, Piedade, Martins, Laura, Cardoso, Margarida, Morais, Nuno, Alves, Nuno, Faria, Paula, Mateus, Artur, Morouço, Pedro, Ferreira, Nelson, Cardoso, Andreia, Lopes, Albino, Soares, Valter, Dias, Tiago, Vardasca, Ricardo, Gabriel, Joaquim, Paredes, Hugo, Reis, Arsénio, Marinho, Sara, Filipe, Vítor, Lains, Jorge, Barroso, João, Da Motta, Carolina, Carvalho, Célia B., Peixoto, Ermelindo, Gomes, Ana A., Costa, Vanessa, Couto, Diana, Marques, Daniel R., Leitão, José A., Tavares, José, Azevedo, Maria H., Silva, Carlos F., Freitas, João, Garcia-Gordillo, Miguel A., Collado-Mateo, Daniel, Chen, Gang, Iezzi, Angelo, Sala, José A., Parraça, José A., Gusi, Narcis, Sousa, Jani, Jardim, Jacinto, Pereira, Anabela, Simões, Sónia, Sardo, Pedro, Guedes, Jenifer, Machado, Paulo, Benevides, Joana, Sousa, Marina, Cabral, Joana, Carvalho, Rosa, Alves, Juliana, Azevedo, Mª Helena, Silva, Carlos, Lee, Huei D., Spolaôr, Newton, Oliva, Jefferson T., Chung, Wu F., Bairros, Keila, Silva, Cláudia D., Souza, Clóvis A., Schroeder, Silvana S., Araújo, Elsa, Monteiro, Helena, Costa, Ricardo, Torgal, Jorge, Henriques, Carolina G., Santos, Luísa, Caceiro, Elisa F., Ramalho, Sónia A., Afreixo, Vera, Santos, João, Mota, Priscilla, Pimentel, Francisco, Caldeira, Suzana N., Ribeiro, Lígia C., Aquino, Priscila S., Ribeiro, Samila G., Pinheiro, Ana B., Lessa, Paula A., Oliveira, Mirna F., Brito, Luísa S., Pinto, Ítalo N., Furtado, Alessandra S., Castro, Régia B., Aquino, Caroline Q., Martins, Eveliny S., Pinheiro, Ana B, Oliveira, Lara L., Pinheiro, Patrícia C., Sousa, Caroline R., Freitas, Vívien A., Silva, Tatiane M., Lima, Adman S., Andrade, Karizia V., Oliveira, Camila A., Vidal, Eglidia F., Ganho-Ávila, Ana, Moura-Ramos, Mariana, Gonçalves, Óscar, Almeida, Jorge, Silva, Armando, Brito, Irma, Amado, João, Rodrigo, António, Gomes, Fernando, Luís, Sara, Cavalheiro, Luís, Gonçalves, Rui, Lopes, Rui S., Fiorin, Bruno H., Santos, Marina S., Oliveira, Edmar S., Moreira, Rita L., Oliveira, Elizabete A., Filho, Braulio L., Palmeira, Lara, Garcia, Teresa, Cardoso, Sara, Oliveira, Sara, Campos, Mariana, Gaudêncio, Iris, Martins, Fernando, Ferreira, Lino, Lopes, Nuno, Marques, Ana R., Carvalho, Rui, Costa, Pablo O., Silva, Maiza M., Alvarenga-Martins, Nathália, Pinto, Paulo F., Oliveira, Denize C., Parreira, Pedro D., Gomes, Antônio T., Lage, Isabel, Cabrita, José, Teixeira, Laetitia, Silva, Sara, Cordeiro, Eugénio, Pimentel, João, Ferro-Lebres, Vera, Souza, Juliana A., Tavares, Mariline, Passadouro, Rui, Peralta, Teresa, Ferreira, Carlos, Lourenço, Georgina, Honório, Samuel, Simões, Alexandra, Carvalho, Lucinda, Figueiredo, Daniela, Valente, Carolina, Ribas, Patrícia, Brandão, Frederico, Sousa, Cesar, Mendes, Francisco, Fernandes, Rosina, Martins, Emília, Magalhães, Cátia, Araújo, Patrícia, Grande, Carla, Vieitez, Juan G., Bianchini, Bruna, Costa, Tânia, Almeida, Armando, Baffour, Gabriel, Laranjeira, Carlos, Guerra, Magda, Barbeiro, Ana P., Ferreira, Regina, Lopes, Sara, Nunes, Liliana, Martins, Julian, Magajewski, Flávio, Soares, Célia, Marques, António, Batista, Marco, Castuera, Ruth J., Mesquita, Helena, Faustino, António, Santos, Jorge, Vizzotto, Betina P., Frigo, Leticia, Pivetta, Hedioneia F., Sardo, Dolores, Abreu, Wilson, Figueiredo, Mª Céu, Jimenez-Castuera, Ruth, Silveira, Paulo, Oliveira, Catarina, Rodriguez, Cláudia K., Kretzer, Márcia R., Nazário, Nazaré O., Cruz, Pedro, Vaz, Daniela C., Ruben, Rui B., Avelelas, Francisco, Silva, Susana, Campos, Mª Jorge, Almeida, Maria, Gonçalves, Liliana, Antunes, Lígia, Simões, João, Cardoso, Susana, Loureiro, Isabel, Santos, Flávia, Alves, Gilberto, Soar, Cláudia, Marsi, Teresa O., Silva, Ernestina, Pedrosa, Dora, Leça, Andrea, Gomes, Maria, Fernandes, Paula, Noné, Ana, Combadão, Jaime, Ramalhete, Cátia, Figueiredo, Paulo, Caeiro, Patrícia, Fontana, Karine C., Machado, Patrícia O., Borges, Raphaelle, Barbosa, Flávio, Sá, Dayse, Brunhoso, Germana, Aparício, Graça, Carvalho, Amâncio, Garcia, Ana P., Santos, Adriana, Brás, Carina, Carvalho, Inês, Batalha, Joana, Glória, Margarida, Bexiga, Filipa, Paraíso, Nilson, Lima, Cristóvão F., Dias, Alberto P., Espada, Mário, Marques, Mário, Veiga-Branco, Mª, Lima, Vera, Cruz, Graça, Barreiros, Luísa, Duarte, Catarina, Lima, Teresa Maneca, Medina, María S., Blanco, Valeriana G., Lopes, Elisa, Virgolino, Ana, Ambrósio, Sara, Almeida, Inês, Marques, Tatiana, Heitor, Mª João, Olivares, Pedro R., Oliveira, Anabela, Cheio, Mónica, Pereira, Olívia R., Pinto, Sara, Oliveira, Adriana, Manso, M. Conceição, Sousa, Carla, Vinha, Ana F., Machado, Mª Manuela, Vieira, Margarida, Fernandes, Beatriz, Tomás, Teresa, Quirino, Diogo, Desouzart, Gustavo, Matos, Rui, Bordini, Magali, Mouroço, Pedro, Matos, Ana R., Serapioni, Mauro, Costa, André, Ribeiro, João, Lobato, João, Martin, Inmaculada Z., Björklund, Anita, Tavares, Aida I., Tavares, Nuno, Valente, João, Ortiga, Angela B., Calvo, Mª Cristina, Natal, Sônia, Pereira, Marta, Prata, Ana R., Nelas, Paula, Carneiro, Juliana, Couto, Cristina, Souza, Géssica M., Almada, Lívia F., Conceição, Milena A., Domingues, Gabriela, Ferreira, Irina, Costa, Ana R., Cardoso, Américo, Meireles, Alexandra, Vieira, Viviane L., Vincha, Kellem R., Cervato-Mancuso, Ana Mª, Faria, Melissa, Reis, Cláudia, Cova, Marco P., Ascenso, Rita T., Almeida, Henrique A., Oliveira, Eunice G., Santana, Miguel, Pereira, Rafael, Jesus, Rita, Tapadas, Rodrigo, Tim-Tim, Carolina, Cezanne, Catarina, Lagoa, Matilde, Lopes, João, Almeida, Henrique, Amado, Sandra, Carrão, Luís, Saboga-Nunes, Luís, Oliveira, Suzete, Escoval, Ana, Assunção, Victor, Luís, Henrique, Luís, Luís, Fotschl, Ulrike, Lirk, Gerald, Silva, Paula A., Ruivo, Joana, Silva, Vânia, Ferraz, Vera, Neves, Joel, Correia, Telma, Amorim, Helena, Pereira, Elsa S., Santos, Leonino S., Reis, Ana S., Rombo, João, Fernandes, Jorge C., Freire, Ana, Francisco, Irene, Louro, Mª Clarisse, Lopes, Saudade, Oliveira, Ana P., Gordo, Sara, Queirós, Paulo, Rodrigues, Teresa, Lobão, Catarina, Moura, Cynthia B., Dreyer, Laysa C., Meneghetti, Vanize, Cabral, Priscila P., Pinto, Francisca, Esteves, Mª Raquel, Galvão, Sofia, Tytgat, Ite, Casas-Novas, Mónica, Bernardo, Helena, Sousa, Gracinda, Sousa, Ana P., Belo, Pedro, Martins, Fátima, Pulido-Fuentes, Montserrat, Cabral, Gil, Prado, Alessandro, Carvalho, Yara M., Campos, Maria, Moreira, Liliana, Ferreira, José, and Teixeira, Ana
Abstract: S1 Health literacy and health education in adolescence
Published: 2016

45. The Stimulus Power Consumption as Form: The Impact on the Environment

Author: Vieira, Gabriella de Castro, Vasconcelos, Carlos Frederico Saraiva de, Vieira, Gabriella de Castro, and Vasconcelos, Carlos Frederico Saraiva de
Abstract: This paper discusses the power of the consumer, encouraging consumption and environmental impacts. The overall objective of this article is to analyze how the power has been practiced in post-modern society, with the central axis unbridled consumption and environmental consequences. Therefore, a general approach is held on the importance of the consumer to the market, the legal provisions which protect you, the power of the advertising industry, especially the compulsive consumerism. Subsequently, we analyze the environmental impacts and discusses the responsibility of all stakeholders about conscious consumption and sustainability., O presente trabalho aborda o poder do consumidor, o incentivo ao consumismo e os impactos no meio ambiente. O objetivo geral do artigo é analisar como o poder tem sido praticado na sociedade pós-moderna, tendo por eixo central o consumo desenfreado e os reflexos ambientais. Para tanto, é realizada uma abordagem geral acerca da importância do consumidor para o mercado, os dispositivos legais que lhe tutelam, o poder do setor publicitário, destacando-se o consumismo compulsivo. Posteriormente, analisam-se os impactos ambientais e discute-se a responsabilidade de todos os agentes a respeito do consumo consciente e a sustentabilidade.
Published: 2016

46. The Stimulus Power Consumption as Form: The Impact on the Environment

Author: Vieira, Gabriella de Castro, Vasconcelos, Carlos Frederico Saraiva de, Vieira, Gabriella de Castro, and Vasconcelos, Carlos Frederico Saraiva de
Abstract: This paper discusses the power of the consumer, encouraging consumption and environmental impacts. The overall objective of this article is to analyze how the power has been practiced in post-modern society, with the central axis unbridled consumption and environmental consequences. Therefore, a general approach is held on the importance of the consumer to the market, the legal provisions which protect you, the power of the advertising industry, especially the compulsive consumerism. Subsequently, we analyze the environmental impacts and discusses the responsibility of all stakeholders about conscious consumption and sustainability., O presente trabalho aborda o poder do consumidor, o incentivo ao consumismo e os impactos no meio ambiente. O objetivo geral do artigo é analisar como o poder tem sido praticado na sociedade pós-moderna, tendo por eixo central o consumo desenfreado e os reflexos ambientais. Para tanto, é realizada uma abordagem geral acerca da importância do consumidor para o mercado, os dispositivos legais que lhe tutelam, o poder do setor publicitário, destacando-se o consumismo compulsivo. Posteriormente, analisam-se os impactos ambientais e discute-se a responsabilidade de todos os agentes a respeito do consumo consciente e a sustentabilidade.
Published: 2016

47. A construção do pensar: uma abordagem a partir do uso das TDIC no ensino de matemática

Author: Santos, Katia Maria Limeira, Vasconcelos, Carlos Alberto de, Santos, Katia Maria Limeira, and Vasconcelos, Carlos Alberto de
Abstract: The construction of thought is inherent in man. However, while teaching mathematics from the use of ICT as soon enable help students develop the ability to think and your creativity. For this it is necessary new definitions, concepts and perspectives on research and education in mathematics and the teaching practice onthe use of ICT. This time this paper aims to address the ICT in the teaching of mathematics, in order to think the student nowadays. methodology was used a qualitative approach, bibliographical character from theoretical assumptions (Barros, Castells, Levy, Primo, Silva and others that deal with the theme). The study highlights the importance of ICT and its use in education, particularly through mathematical software, revealing innovate in teaching mathematics including the role of ICT from a new teaching of science, enabling the cognitive development of the student, A construção do pensar, é inerente ao homem. Contudo, ao ensinar a matemática a partir do uso das TIC, logo possibilitará ajudar o aluno a desenvolver a capacidade de pensar e sua criatividade. Para isso se faz necessário novas definições, concepções e perspectivas sobre a pesquisa e ensino na matemática, bem como a prática pedagógica acerca do uso das TIC. Dessa feita esse texto objetiva tratar das TIC no ensino de matemática, visando o pensar do aluno na contemporaneidade. Utilizou-se metodologia com abordagem qualitativa, de caráter bibliográfico a partir de pressupostos teóricos (Barros, Castells, Levy, Primo, Silva dentre outros que abordam a temática). O estudo destaca a importância das TIC e seu uso na educação, em especial através de softwares matemático, revelando o inovar no ensino da matemática compreendendo o papel das TIC, a partir de uma nova didática das ciências, possibilitando o desenvolvimento cognitivo do aluno., La construcción de pensamiento es inherente en el hombre. Sin embargo, mientras que la enseñanza de las matemáticas de la utilización de las TIC tan pronto permitirá a los estudiantes de la ayuda desarrollan la capacidad de pensar y su creatividad. Para ello, es necesario nuevas definiciones, conceptos y perspectivas en la investigación y la educación en matemáticas y la práctica de la enseñanza en el uso de las TIC. Esta vez el presente trabajo pretende abordar la TIC en la enseñanza de las matemáticas, con el fin de pensar al estudiante en la actualidad. metodología se utilizó un enfoque cualitativo, de carácter bibliográfico de los supuestos teóricos (Barros, Castells, Levy, Primo, Silva y otros que tienen que ver con el tema). El estudio pone de relieve la importancia de las TIC y su uso en la educación, especialmente a través de software matemático, revelando innovar en la enseñanza de matemáticas, incluyendo el papel de las TIC a partir de una nueva enseñanza de la ciencia, lo que permite el desarrollo cognitivo del alumno.
Published: 2016

48. O que é educação

Author: Vasconcelos, Carlos Alberto, Santos Soares, Vando Kleber, Vasconcelos, Carlos Alberto, and Santos Soares, Vando Kleber
Abstract: Resenha: PEREIRA, P. A. O que é pesquisa em educação? 2. ed. São Paulo: Paulus, 2008.
Published: 2016

49. O que é educação

Author: Vasconcelos, Carlos Alberto, Santos Soares, Vando Kleber, Vasconcelos, Carlos Alberto, and Santos Soares, Vando Kleber
Abstract: Resenha: PEREIRA, P. A. O que é pesquisa em educação? 2. ed. São Paulo: Paulus, 2008.
Published: 2016

50. PXK locus in systemic lupus erythematosus : fine mapping and functional analysis reveals novel susceptibility gene ABHD6

Author: Oparina, Nina Y., Delgado-Vega, Angelica M., Martinez-Bueno, Manuel, Magro-Checa, Cesar, Fernandez, Concepcion, Ortega Castro, Rafaela, Pons-Estel, Bernardo A., D'Alfonso, Sandra, Sebastiani, Gian Domenico, Witte, Torsten, Lauwerys, Bernard R., Endreffy, Emoke, Kovacs, Laszlo, Escudero, Alejandro, Lopez-Pedrera, Chary, Vasconcelos, Carlos, da Silva, Berta Martins, Frostegard, Johan, Truedsson, Lennart, Martin, Javier, Raya, Enrique, Ortego-Centeno, Norberto, de los Angeles Aguirre, Maria, de Ramon Garrido, Enrique, Castillo Palma, Maria-Jesus, Alarcon-Riquelme, Marta E., Kozyrev, Sergey V., Oparina, Nina Y., Delgado-Vega, Angelica M., Martinez-Bueno, Manuel, Magro-Checa, Cesar, Fernandez, Concepcion, Ortega Castro, Rafaela, Pons-Estel, Bernardo A., D'Alfonso, Sandra, Sebastiani, Gian Domenico, Witte, Torsten, Lauwerys, Bernard R., Endreffy, Emoke, Kovacs, Laszlo, Escudero, Alejandro, Lopez-Pedrera, Chary, Vasconcelos, Carlos, da Silva, Berta Martins, Frostegard, Johan, Truedsson, Lennart, Martin, Javier, Raya, Enrique, Ortego-Centeno, Norberto, de los Angeles Aguirre, Maria, de Ramon Garrido, Enrique, Castillo Palma, Maria-Jesus, Alarcon-Riquelme, Marta E., and Kozyrev, Sergey V.
Abstract: Objectives To perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease. Methods Linkage disequilibrium (LD) mapping was conducted by using 1251 SNPs (single nucleotide polymorphism) covering a 862 kb genomic region on 3p14.3 comprising the PXK locus in 1467 SLE patients and 2377 controls of European origin. Tag SNPs and genotypes imputed with IMPUTE2 were tested for association by using SNPTEST and PLINK. The expression QTLs data included three independent datasets for lymphoblastoid cells of European donors: HapMap3, MuTHER and the cross-platform eQTL catalogue. Correlation analysis of eQTLs was performed using Vassarstats. Alternative splicing for the PXK gene was analysed on mRNA from PBMCs. Results Fine mapping revealed long-range LD (>200 kb) extended over the ABHD6, RPP14, PXK, and PDHB genes on 3p14.3. The highly correlated variants tagged an SLE-associated haplotype that was less frequent in the patients compared with the controls (OR=0.89, p=0.00684). A robust correlation between the association with SLE and enhanced expression of ABHD6 gene was revealed, while neither expression, nor splicing alterations associated with SLE susceptibility were detected for PXK. The SNP allele frequencies as well as eQTL pattern analysed in the CEU and CHB HapMap3 populations indicate that the SLE association and the effect on ABHD6 expression are specific to Europeans. Conclusions These results confirm the genetic association of the locus 3p14.3 with SLE in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. We suggest a pathogenic mechanism mediated by the upregulation of ABHD6 in individuals carrying the SLE-risk variants.
Published: 2015
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