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2. A pilot study of peripheral blood DNA methylation models as predictors of knee osteoarthritis radiographic progression: data from the Osteoarthritis Initiative (OAI).

Author

M Dunn, Christopher, Nevitt, Michael C, Lynch, John A, and Jeffries, Matlock A

Subjects
Knee Joint, Leukocytes, Mononuclear, Humans, Osteoarthritis, Knee, Disease Progression, Radiography, Longitudinal Studies, Pilot Projects, DNA Methylation, Epigenesis, Genetic, Models, Genetic, Middle Aged, Female, Male, Biomarkers, Epigenesis, Genetic, Leukocytes, Mononuclear, Models, Osteoarthritis, Knee
Abstract

Knee osteoarthritis (OA) is a leading cause of chronic disability worldwide, but no diagnostic or prognostic biomarkers are available. Increasing evidence supports epigenetic dysregulation as a contributor to OA pathogenesis. In this pilot study, we investigated epigenetic patterns in peripheral blood mononuclear cells (PBMCs) as models to predict future radiographic progression in OA patients enrolled in the longitudinal Osteoarthritis Initiative (OAI) study. PBMC DNA was analyzed from baseline OAI visits in 58 future radiographic progressors (joint space narrowing at 24 months, sustained at 48 months) compared to 58 non-progressors. DNA methylation was quantified via Illumina microarrays and beta- and M-values were used to generate linear classification models. Data were randomly split into a 60% development and 40% validation subsets, models developed and tested, and cross-validated in a total of 40 cycles. M-value based models outperformed beta-value based models (ROC-AUC 0.81 ± 0.01 vs. 0.73 ± 0.02, mean ± SEM, comparison p = 0.002), with a mean classification accuracy of 73 ± 1% (mean ± SEM) for M- and 69 ± 1% for beta-based models. Adjusting for covariates did not significantly alter model performance. Our findings suggest that PBMC DNA methylation-based models may be useful as biomarkers of OA progression and warrant additional evaluation in larger patient cohorts.

Published
2019

12. Sex-Linked Discrepancies in C57BL6/J Mouse Osteoarthritis are Associated With the Gut Microbiome and are Transferrable by Microbiome Transplantation.

Author

Schlupp, Leoni, Prinz, Emmaline, Dyson, Gabriella, Barrett, Montana, Izda, Vladislav, Dunn, Christopher M., and Jeffries, Matlock A.

Subjects
CECUM microbiology, MENISCUS surgery, METAPLASTIC ossification, LIPOPOLYSACCHARIDES, CYTOKINES, SYNOVITIS, SEQUENCE analysis, GUT microbiome, ANIMAL experimentation, SEX distribution, SEVERITY of illness index, IMMUNOASSAY, COMPARATIVE studies, OSTEOARTHRITIS, HISTOLOGY, MICE
Abstract

Objective. Females have reduced osteoarthritis (OA) in surgical models. The objective of the current study was to evaluate a sex-linked gut microbiome in the pathogenesis of OA. Methods. We induced OA via destabilization of the medial meniscus surgery in adult male and female C57BL6/J mice with and without opposite-sex microbiome transplantation. Eight weeks later, animals were euthanized, and OA severity, synovitis, and osteophyte scores were determined. Serum lipopolysaccharide was measured chromogenically, and serum cytokines were quantified via multiplex immunoassay. Cecal microbiome profiles were generated using 16S deep sequencing. Results. Males had worse OA histology (3.5x, P = 6 × 10−7 ), synovitis (2.4x, P = 5 × 10−4 ), and osteophyte scores (3.7x, P = 3 × 10−4 ) than females. Male-into-female transplantation worsened all outcomes (histology 1.8x, P = 0.02; synovitis 2.0x, P = 3 × 10−5 ; osteophyte 2.1x, P = 0.01) compared to females, whereas female-into-male transplantation improved all outcomes except for synovitis (histology 0.53x, P = 2 × 10−4 ; osteophyte 0.28x, P = 5 × 10−4 ) compared to males. In the gut microbiome analysis, 44 clades were different in at least one group comparison; 5 clades were correlated with the Osteoarthritis Research Society International score (Lactobacillus R = −0.40, Aldercreutzia R = −0.40, rc4_4 R = −0.55, Sutterella R = −0.37, and Clostridiales R = 0.36). In the cytokine analysis, 10 analytes were different in at least one group comparison; 3 were different in two groups (female and female-into-male transplants vs male comparisons, all reduced in female and female-into-male transplants), including interleukin-12 (0.66x, P = 0.02; 0.66x, P = 0.02, respectively), eotaxin (0.74x, P = 5 × 10−6 ; 0.57x, P = 0.03), and tumor necrosis factor α (0.49x, P = 0.03; 0.52x, P = 0.009). Conclusion. Sex-linked differences in the mouse gut microbiome are associated with OA outcomes, are reversible by opposite-sex microbiome transplantation, and are associated with serum cytokine changes. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Peripheral Blood DNA Methylation–Based Machine Learning Models for Prediction of Knee Osteoarthritis Progression: Biologic Specimens and Data From the Osteoarthritis Initiative and Johnston County Osteoarthritis Project

Author

Dunn, Christopher M., primary, Sturdy, Cassandra, additional, Velasco, Cassandra, additional, Schlupp, Leoni, additional, Prinz, Emmaline, additional, Izda, Vladislav, additional, Arbeeva, Liubov, additional, Golightly, Yvonne M., additional, Nelson, Amanda E., additional, and Jeffries, Matlock A., additional

Published
2022
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24. Peripheral Blood DNA Methylation–Based Machine Learning Models for Prediction of Knee Osteoarthritis Progression: Biologic Specimens and Data From the Osteoarthritis Initiative and Johnston County Osteoarthritis Project.

Author

Dunn, Christopher M., Sturdy, Cassandra, Velasco, Cassandra, Schlupp, Leoni, Prinz, Emmaline, Izda, Vladislav, Arbeeva, Liubov, Golightly, Yvonne M., Nelson, Amanda E., and Jeffries, Matlock A.

Subjects
KNEE osteoarthritis, DISEASE progression, BIOMARKERS, MACHINE learning, DNA methylation, DESCRIPTIVE statistics, PREDICTION models, COLLECTION & preservation of biological specimens, EPIGENOMICS
Abstract

Objective: The lack of accurate biomarkers to predict knee osteoarthritis (OA) progression is a key unmet need in OA clinical research. The objective of this study was to develop baseline peripheral blood epigenetic biomarker models to predict knee OA progression. Methods: Genome‐wide buffy coat DNA methylation patterns from 554 individuals from the Osteoarthritis Biomarkers Consortium (OABC) were determined using Illumina Infinium MethylationEPIC 850K arrays. Data were divided into model development and validation sets, and machine learning models were trained to classify future OA progression by knee pain, radiographic imaging, knee pain plus radiographic imaging, and any progression (pain, radiographic, or both). Parsimonious models using the top 13 CpG sites most frequently selected during development were tested on independent samples from participants in the Johnston County Osteoarthritis (JoCo OA) Project (n = 128) and a previously published Osteoarthritis Initiative (OAI) data set (n = 55). Results: Full models accurately classified future radiographic‐only progression (mean ± SEM accuracy 87 ± 0.8%, area under the curve [AUC] 0.94 ± 0.004), pain‐only progression (accuracy 89 ± 0.9%, AUC 0.97 ± 0.004), pain plus radiographic progression (accuracy 72 ± 0.7%, AUC 0.79 ± 0.006), and any progression (accuracy 78 ± 0.4%, AUC 0.86 ± 0.004). Pain‐only and radiographic‐only progressors were not distinguishable (mean ± SEM accuracy 58 ± 1%, AUC 0.62 ± 0.001). Parsimonious models showed similar performance and accurately classified future radiographic progressors in the OABC cohort and in both validation cohorts (mean ± SEM accuracy 80 ± 0.3%, AUC 0.88 ± 0.003 [using JoCo OA Project data], accuracy 80 ± 0.8%, AUC 0.89 ± 0.002 [using previous OAI data]). Conclusion: Our data suggest that pain and structural progression share similar early systemic immune epigenotypes. Further studies should focus on evaluating the pathophysiologic consequences of differential DNA methylation and peripheral blood cell epigenotypes in individuals with knee OA. [ABSTRACT FROM AUTHOR]

Published
2023
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28. Contributors

Author

Abelson, Abby G., Abraham, Mary, Abramson, Steven B., Adachi, Jonathan D., Aggarwal, Rohit, Akira, Shizuo, Aletaha, Daniel, Ashraf Ali, Amjid, Allem, Kavitta B., Almehthel, Mohammed, Almohaya, Mohammed, Riera Alonso, Elena, Amigo, Mary-Carmen, Aringer, Martin, Arkema, Elizabeth V., Ascherman, Dana P., Atamas, Sergei P., Atkinson, Timothy J., Azeez, Maha A., Baer, Alan N., Baraliakos, Xenofon, Bardin, Thomas, Barnsley, Leslie, Barr, Andrew J., Bathon, Joan M., Belch, Jill J.F., Bellido, Teresita, Ben-Artzi, Ami, Benedetti, Fabrizio, Bennell, Kim L., Bennett, Sarah E., Berard, Roberta A., Berenbaum, Francis, Berman, Brian, Bermas, Bonnie L., Elizabeth Berry, Alice, Bertsias, George, Bhana, Suleman, Bhattacharyya, Shamik, Bilginer, Yelda, Bleasel, Jane F., Block, Joel A., Böhm, Markus, Bonelli, Michael, Boumpas, Dimitrios T., Bozec, Aline, Brasington, Richard D., Braun, Jürgen, Brouwer, Elisabeth, Brown, Jacques P., Brown, Matthew A., Brown, Matthew L., Buch, Maya H., Buckley, Christopher D., Bugbee, William D., Burmester, Gerd-Rüdiger, Burns, Jane C., Burr, David B., Buttgereit, Frank, Buxbaum, Joel N., Bykerk, Vivian P., Calabrese, Cassandra, Calabrese, Leonard H., Callen, Jeffrey P., Carr, Andrew J., Carrino, John A., Cavallo, Sabrina, Cervera, Ricard, Chang, Christopher, Chang, Joyce C., Chaon, Benjamin C., Chaudhary, Prateek, Choi, Hyon K., Choy, Ernest H.S., Christopher-Stine, Lisa, Chung, Lorinda, Ciccia, Francesco, Clauw, Daniel J., Clinch, Jacqui, Clowse, Megan E.B., Coghlan, John (Gerry), Colbert, Robert A., Conaghan, Philip G., Cooper, Cyrus, Costello, Wendy, Costenbader, Karen H., Cox, George L.D., Creamer, Paul, Cronstein, Bruce N., Cross, Raymond K., Curtis, Jeffrey R., D'Adamo, Chris, D'Agati, Vivette D., Daikh, David I., Dakin, Stephanie G., Dalbeth, Nicola, Davis, Aileen M., D'Cruz, David P., Eduardo de Barros Branco, Carlos, de Boer, Berber, De Craemer, Ann-Sophie, de Jesus, Adriana A., De Vita, Salvatore, de Wit, Maarten, Deal, Chad L., Deane, Kevin D., Dellaripa, Paul F., Dennison, Elaine, Denton, Christopher P., DiCarlo, Edward F., Distler, Oliver, Donlan, Pamela, Doyle, Tracy J., du Preez, Hannah, Dyer, George S.M., Eastell, Richard, Ehrchen, Jan, Elewaut, Dirk, Emery, Paul, Emmerling, Max R., Espinosa, Gerard, Espinoza, Luis R., Eyre, Stephen, Fanouriakis, Antonis, Farber, Joshua, Fasth, Anders, Feist, Eugen, Feldman, Candace H., Fernandez-Ruiz, Ruth, Filer, Andrew, Fiorentino, David F., Fisher, Benjamin A., Fisk, John D., Flajnik, Martin F., Forbess, Lindsy, Fox, David A., Frech, Tracy M., Frisaldi, Elisa, Gabay, Cem, Gadina, Massimo, Gandolfo, Saviana, Garelick, Daniela, Gay, Steffen, Geifman, Nophar, George, Michael D., Eric Gershwin, M., Ghadiali, Jay, Gilis, Elisabeth, Gold, Deborah T., Gold, Garry E., Goldbach-Mansky, Raphaela, Gómez-Puerta, José A., Goodman, Susan M., Gordon, Caroline, Gordon, Sharon, Gossec, Laure, Grainger, Andrew J., Grainger, Rebecca, Gravallese, Ellen M., Greenberg, Jeffrey D., Guglielmi, Luiza Guilherme, Gül, Ahmet, Gullapalli, Rao P., Guma, Monica, Gupta, Sarthak, Han, Shuhong, Hanly, John G., Hanson, Eric P., Haraoui, Boulos, Harley, John B., Haroun, Tayseer G., Hashkes, Philip J., Hasni, Sarfaraz A., Bassim Hassan, Andrew, Haupt, Lukas, Hausmann, Jonathan S., Hawker, Gillian A., Heiberg, Turid, Helfgott, Simon M., Hinman, Rana S., Hoffmann-Vold, Anna-Maria, Holroyd, Christopher R., Holt, Cathy, Horomanski, Audra, Huizinga, Thomas W.J., Humby, Frances, Elaine Husni, M., Hwang, Jonathan, Hyrich, Kimme, Inman, Robert D., Inoue, Dai, Isaac, Zacharia, Isaacs, John D., Isenberg, David, Iversen, Maura D., Jabs, Douglas A., James, Judith A., Jandali, Bochra, Kassim Javaid, M., Javier, Rose-Marie, Jefferis, Roy, Jeffries, Matlock A., Johnson, Sindhu R., Johnstone, Brian, Helena Jonsson, Anna, Joyce, Andrew A., Jung, Michelle, Kado, Ruba, Kaisho, Tsuneyasu, Kamal, Natasha, Kane, David, Kaplan, Mariana J., Karr, Timothy L., Kassimos, Dimitrios G., Kastner, Daniel L., Katz, Jeffrey N., Kawano, Mitsuhiro, Kay, Jonathan, Keating, Richard M., Kelly, Jennifer A., Kendler, David, Keyser, Randall E., Khamashta, Munther A., Khanna, Dinesh, Khokhar, Kiran, Kiefer, David, King, Lauren K., Kloppenburg, Margreet, Kolasinski, Sharon L., Kolstad, Kathleen D., Kottyan, Leah C., Byers Kraus, Virginia, Kronberger, Leo R.W., Kroopnick, Jeffrey M., Kvien, Tore K., LaBaer, Joshua, Lafyatis, Robert, Lakkis, Jay I., Landewé, Robert B.M., Langford, Carol A., Laster, Marciana L., Latourte, Augustin, Lau, Arthur N., Laurynenka, Viktoryia, Lavin, Robert A., Laxer, Ronald M., Li, Suzanne C., Liao, Katherine P., Lieberman, Scott M., Liew, Jean W., Littlejohn, Geoffrey O., Liu, Eva S., Lo, Lawrence, Lories, Rik J., Luger, Thomas A., Lundberg, Ingrid E., Luqmani, Raashid A., Machado, Pedro M., Machold, Klaus P., Ronald MacKenzie, C., Major, Tanya J., Malfait, Anne-Marie, Malley, Tamir, Manasson, Julia, March, Lyn M., Olivé Marqués, Alejandro, Márquez, Javier, Martin, Paul, Martínez-Lavín, Manuel, Matteson, Eric L., Mayes, Maureen D., McAlindon, Timothy, McCarthy, Edward F., McCarthy, Geraldine M., McDermott, Michael F., McDonnell, Patrick J., McGonagle, Dennis, Simon Meara, Alexa, Mehta, Jay J., Melville, Andrew R., Merola, Joseph F., Micheletti, Robert G., Michou, Laëtitia, Middleton, Rob, Midha, Disha, Mikdashi, Jamal A., Miller, Frederick W., Minden, Kirsten, Miner, Jonathan J., Minhas, Deeba, Helene Moe, Rikke, Möller, Ingrid, Mopuru, Renuka, Mortaji, Parisa, Mueller, Alisa A., Myasoedova, Elena, Namur, Gauthier, Naredo, Esperanza, Navarro-Compán, Victoria, Neerinckx, Barbara, Nelson, Amanda E., Nerviani, Alessandra, Nicolson, Philippa J.A., Nordal, Ellen B., Nöth, Ulrich, Ntatsaki, Eleana, Obenhuber, Tilman, Oddis, Chester V., Ogdie-Beatty, Alexis R., Omar, Ahmed, Ombrello, Michael J., Omisade, Antonina, Onel, Karen B., Ong, Voon H., Orcel, Philippe, Orozco, Gisela, Orr, Carl, O'Shea, John J., Ospelt, Caroline, Østensen, Monika, Özen, Seza, Park, Elizabeth, Parker, Matthew J.S., Pathan, Ejaz, Patrono, Carlo, Perez-Chada, Lourdes M., Pijnenburg, Luc, Pillinger, Michael H., Pineda, Carlos, Pipitone, Nicolò, Pitzalis, Costantino, Poddubnyy, Denis, Pope, Janet E., Postolova, Anna, Price, Andrew J., Pryor, Katherine P., Quartuccio, Luca, Rackwitz, Lars, Radner, Helga, Rajendran, Aardra, Ramiro, Sofia, Raychaudhuri, Soumya, Redmond, Anthony C., Reeves, Westley H., Remmers, Elaine F., Requena, Luis, Reynolds, Gary, Reynolds, John A., Ribbens, Clio, Richards, Bethan, Richardson, Bruce, Richette, Pascal, Ritchlin, Christopher T., Ritter, Susan Y., Robinson, Philip C., Robinson, William H., Rogers, Valerie J., Romain, Paul L., Rosas, Ivan O., Rosenthal, Ann K., Rubin, Elka, Rudwaleit, Martin, Rutgers, Bram A., Rygg, Marite, Saag, Kenneth G., Salmon, Jane E., Salusky, Isidro B., Salvarani, Carlo, Sandell, Linda J., Sandhu, Vaneet K., Sandovici, Maria, Sand-Svartrud, Anne-Lene, Scanzello, Carla R., Schaible, Hans-Georg, Scher, Jose U., Schett, Georg, Schiffenbauer, Adam I., Schiller, Alan L., Schlesinger, Naomi, Schreiber, Benjamin E., Schwartz, Daniella M., Shaibani, Aziz, Sharma, Leena, Shmerling, Robert H., Siaton, Bernadette C., Siegel, Richard M., Sieghart, Daniela, Silverman, Stuart L., Simard, Julia F., Simmons, Barry P., Simms, Robert W., Singer, Nora G., Sirotich, Emily, Smith, Judith A., Smith, Stacy E., Smolen, Josef S., Solomon, Daniel H., Sparks, Jeffrey A., Stack, John, Stanley, David, Steen, Virginia D., Steere, Allen C., Stegeman, Coen A., Steiner, Günter, Steinert, Andre F., Stojan, George, Strand, Vibeke, Sufka, Paul, Sullivan, James K., Szulc, Pawel, Tang, Chen, Tang, Shiyu, Taylor, Peter C., Terkeltaub, Robert, Thomas, Afton R., Thorne, Jennifer E., Topping, Louise M., Toprover, Michael, Torralba, Karina, Touma, Zahi, Tremoulet, Adriana H., Trouw, Leendert, Tuan, Rocky S., Uçkay, Ilker, Umehara, Hisanori, van der Geest, Kornelis S.M., van der Heijde, Désirée, van Gaalen, Floris A., Van Mechelen, Margot, van Vollenhoven, Ronald F., Vandevelde, Claire Y.J., Varga, John, Vassilopoulos, Dimitrios, Veale, Douglas J., Verstappen, Gwenny M., Viatte, Sebastien, Vincent, Tonia L., Vital, Edward M., von Loga, Isabell S., Wahezi, Dawn M., Wallace, Daniel J., Wallace, Zachary S., Warburton, Gary, Watad, Abdulla, Watts, Richard A., Weinblatt, Michael E., Weir, Matthew R., Weisman, Michael H., Weiss, Pamela F., Branford White, Harriet, White, Kenneth E., Wilkinson, David J., Williams, David E., Williams, Richard, Wilson, Hannah, Winthrop, Kevin L., Witt, Claudia M., Witzmann, Gerhard, Wong, John B., Woolf, Anthony D., Paul Wordsworth, B., Xu, Huji, Yazdany, Jinoos, Young, David A., Young, Stephen P., Md Yusof, Md Yuzaiful, and Zhuang, Haoyang

Published
2023
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30. Variants within MECP2, a key transcription regulator, are associated with increased susceptibility to lupus and differential gene expression in patients with systemic lupus erythematosus

Author

Webb, Ryan, Wren, Jonathan D., Jeffries, Matlock, Kelly, Jennifer A., Kaufman, Kenneth M., Tang, Yuhong, Frank, Mark Barton, Merrill, Joan, Kimberly, Robert P., Edberg, Jeffrey C., Ramsey-Goldman, Rosalind, Petri, Michelle, Reveille, John D., Alarcón, Graciela S., Vilá, Luis M., Alarcón-Riquelme, Marta E., James, Judith A., Vyse, Timothy J., Moser, Kathy L., Gaffney, Patrick M., Gilkeson, Gary S., Harley, John B., and Sawalha, Amr H.

Published
2009
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32. Colaboradores

Author

Abramson, Steven B., Aggarwal, Rohit, Ahn, Christine S., An, KaiNan, Andrade, Felipe, Ardoin, Stacy P., Awisat, Abid, Azevedo, Pedro Ming, Barbar-Smiley, Fatima, Barbhaiya, Medha, Barton, Anne, Baughman, Robert P., Beaton, Dorcas E., Beere, Helen M., Behrens, Edward M., Bermas, Bonnie L., Bertsias, George, Bewtra, Meenakshi, Bhardwaj, Nina, Bingham, Clifton O., III, Bockenstedt, Linda K., Boers, Maarten, Boilard, Eric, Boin, Francesco, Boumpas, Dimitrios T., Bozec, Aline, Broderick, Lori, Brown, Matthew, Buckley, Christopher D., Budd, Ralph C., Burg, Nathalie, Cannella, Amy C., Cappelli, Laura C., Carter, John D., Chan, Andrew C., Chang, Christopher, Cheng, Joseph S., Chiodo, Christopher P., Chung, Sharon A., Cleland, Leslie G., Cohen, Stanley, Colbert, Robert A., Cook, Paul P., Craft, Joseph E., Crofford, Leslie J., Cronstein, Bruce N., Crow, Mary K., Crowson, Cynthia S., Cuccurullo, Sara J., Cunnane, Gaye, Curtis, Jeffrey R., Dalbeth, Nicola, Dall’Era, Maria, Darrah, Erika, Dau, Jonathan, Davis, John M., III, De Bari, Cosimo, Debold, Edward P., Dell’Accio, Francesco, DeMarco, Paul J., Diamond, Betty, Di Cesare, Paul E., di Matteo, Andrea, Dixit, Rajiv, Donohue, Kenneth W., Dvergsten, Jeffrey, El-Gabalawy, Hani S., England, Bryant R., Erkan, Doruk, Eyre, Stephen, Fanouriakis, Antonis, Fearon, Ursula, Filer, Andrew, Fiorentino, David F., Firestein, Gary S., Fischer, Saloumeh K., Fishman, Felicity G., FitzGerald, Oliver, Flaherty, John P., Nieves, Cesar E. Fors, Gabriel, Sherine E., Gallentine, William, Gasque, Philippe, Gensler, Lianne S., Gershwin, M. Eric, Goldring, Mary B., Goldring, Steven R., Golightly, Yvonne M., Goodman, Stuart, Graf, Jonathan, Graham, Gerard, Green, Douglas R., Greenspan, Adam, Grimaldi, Christine, Grüneboom, Anika, Guilherme, Luiza, Guillot, Xavier, Haberman, Rebecca, Hajj-Ali, Rula A., Haudenschild, Dominik R., Hellmann, David B., Hoffman, Hal M., Holers, V. Michael, Holmdahl, Rikard, Hsu, Joyce J., Huddleston, James I., III, Hudson, Alan P., Hunder, Gene G., Itoh, Yoshifumi, Jacobs, Johannes W.G., Jaremko, Jacob L., Jeffries, Matlock A., Jen, Ho, Joki, Jaclyn, Jordan, Martha S., Jorizzo, Joseph L., Kalil, Jorge, Kaufman, Kenton R., Kavanaugh, Arthur, Keenan, Robert T., Kenna, Tony, Kerr, Darcy A., Kissin, Eugene Y., Knight, Rob, Kono, Dwight H., Koretzky, Gary A., Korsten, Peter, Kosty, Jennifer, Krakow, Deborah, Kumar, Deepak, Lachmann, Helen J., Lafeber, Floris P.J.G., Lambert, Robert G.W., Lane, Nancy E., Langford, Carol A., Laskin, Daniel M., Lauvau, Gregoire, Lee, Tzielan C., Leverenz, David L., Loeser, Richard F., Lozada, Carlos J., Luke, Ofure, Lundberg, Ingrid E., Luqmani, Raashid, Luyten, Frank P., Mader, Reuven, Magee, Conor, Maksymowych, Walter P., Manger, Bernhard, Markenson, Joseph A., Martin, Scott David, Matteson, Eric L., Maxwell, Lara, McCarthy, Katharine, McInnes, Iain B., Merkel, Peter A., Mikuls, Ted R., Miller, Mark S., Misra, Devyani, Mobasheri, Ali, Moder, Kevin G., Monach, Paul A., Montgomery, Anna, Moulton, Vaishali R., Mulders-Manders, Catharina M., Muniz, Luciana Ribeiro, Murphy, Louise B., Nagaraju, Kanneboyina, Nasser, Rani, Nelson, Amanda E., Neogi, Tuhina, Nigrovic, Peter A., O’Dell, James R., Ogdie, Alexis, Østergaard, Mikkel, Paley, Michael A., Panush, Richard S., Peng, Stanford L., Perlman, Harris, Pillai, Shiv, Pillinger, Michael H., Polston, Gregory R., Porcelli, Steven A., Price, Mark D., Pulles, Astrid E., Raza, Karim, Reddy, Virginia, Reed, Ann M., Reveille, John D., Rhee, Rennie L., Ritchlin, Christopher T., Robinson, Angela B., Rosen, Antony, Rosenbaum, James T., Rosenberg, Andrew E., Ruderman, Eric M., Saag, Kenneth G., Salmon, Jane E., Sammaritano, Lisa R., Samuels, Jonathan, Sandborg, Christy I., Sangeorzan, Adam P., Santora, Arthur C., II, Sattui, Sebastian E., Sawalha, Amr H., Saxena, Amit, Saxena, Mansi, Scanzello, Carla R., Schett, Georg, Semb, Anne Grete, Shah, Ami A., Shah, Binita, Sharpley, Faye A., Sikora, Keith A., Simon, Anna, Siraj, Dawd S., Sorkin, Linda S., Clair, E. William St., Stamp, Lisa K., Stone, John H., Strowd, Lindsay C., Suarez-Fueyo, Abel, Svensson, Camilla I., Sweiss, Nadera J., Swigart, Carrie R., Szekanecz, Zoltán, Tait, Stephen, Tanner, Stacy, Taylor, Peter C., Taylor, William J., Terkeltaub, Robert, Theofilopoulos, Argyrios N., Thornhill, Thomas S., Toprover, Michael, Torok, Kathryn S., Toth, Michael J., Townsend, Michael J., Tozman, Elaine C., Trouw, Leendert A., Tsokos, George C., Tugwell, Peter, Vabret, Nicolas, van der Goes, Marlies C., van der Linden, Sjef, van der Meer, Jos W.M., van Laar, Jacob M., Van Mater, Heather, van Vollenhoven, Ronald F., van Vulpen, Lize F.D., Varga, John, Vasquez, Raul A., Veale, Douglas J., Wakefield, Richard J., Wallace, Mark S., Wang, Ruoning, Wang, Tingting, Werth, Victoria P., Wigley, Fredrick M., Winter, Deborah R., Wofsy, David, Wong, Cyrus C., Yokoyama, Wayne M., Zamore, Richard, Zayat, Ahmed S., Zou, Yong-Rui, and Zurier, Robert B.

Published
2022
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34. Contributors

Author

Abramson, Steven B., Aggarwal, Rohit, Ahn, Christine S., An, KaiNan, Andrade, Felipe, Ardoin, Stacy P., Awisat, Abid, Azevedo, Pedro Ming, Barbar-Smiley, Fatima, Barbhaiya, Medha, Barton, Anne, Baughman, Robert P., Beaton, BScOT, Dorcas E., Beere, Helen M., Behrens, Edward M., Bermas, Bonnie L., Bertsias, George, Bewtra, Meenakshi, Bhardwaj, Nina, Bingham, Clifton O., III, Bockenstedt, Linda K., Boers, Maarten, Boilard, Eric, Boin, Francesco, Boumpas, Dimitrios T., Bozec, Aline, Broderick, Lori, Brown, Matthew, Buckley, Christopher D., Budd, Ralph C., Burg, Nathalie, Cannella, Amy C., Cappelli, Laura C., Carter, John D., Chan, Andrew C., Chang, Christopher, Cheng, Joseph S., Chiodo, Christopher P., Chung, Sharon A., Cleland, Leslie G., Cohen, Stanley, Colbert, Robert A., Cook, Paul P., Craft, Joseph E., Crofford, Leslie J., Cronstein, Bruce N., Crow, Mary K., Crowson, Cynthia S., Cuccurullo, Sara J., Cunnane, Gaye, Curtis, Jeffrey R., Dalbeth, Nicola, Dall’Era, Maria, Darrah, Erika, Dau, Jonathan, Davis, John M., III, De Bari, Cosimo, Debold, Edward P., Dell’Accio, Francesco, DeMarco, Paul J., Diamond, Betty, Di Cesare, Paul E., di Matteo, Andrea, Dixit, Rajiv, Donohue, Kenneth W., Dvergsten, Jeffrey, El-Gabalawy, Hani S., England, Bryant R., Erkan, Doruk, Eyre, Stephen, Fanouriakis, Antonis, Fearon, Ursula, Filer, Andrew, Fiorentino, David F., Firestein, Gary S., Fischer, Saloumeh K., Fishman, Felicity G., FitzGerald, Oliver, Flaherty, John P., Fors Nieves, Cesar E., Gabriel, Sherine E., Gallentine, William, Gasque, Philippe, Gensler, Lianne S., Gershwin, M. Eric, Goldring, Mary B., Goldring, Steven R., Golightly, Yvonne M., Goodman, Stuart, Graf, Jonathan, Graham, Gerard, Green, Douglas R., Greenspan, Adam, Grimaldi, Christine, Grüneboom, Anika, Guilherme, Luiza, Guillot, Xavier, Haberman, Rebecca, Hajj-Ali, Rula A., Haudenschild, Dominik R., Hellmann, David B., Hoffman, Hal M., Holers, V. Michael, Holmdahl, Rikard, Hsu, Joyce J., Huddleston, James I., III, Hudson, Alan P., Hunder, Gene G., Itoh, Yoshifumi, Jacobs, Johannes W.G., Jaremko, Jacob L., Jeffries, Matlock A., Jen, Ho, Joki, Jaclyn, Jordan, Martha S., Jorizzo, Joseph L., Kalil, Jorge, Kaufman, Kenton R., Kavanaugh, Arthur, Keenan, Robert T., Kenna, Tony, Kerr, Darcy A., Kissin, Eugene Y., Knight, Rob, Kono, Dwight H., Koretzky, Gary A., Korsten, Peter, Kosty, Jennifer, Krakow, Deborah, Kumar, Deepak, Lachmann, Helen J., Lafeber, Floris P.J.G., Lambert, Robert G.W., Lane, Nancy E., Langford, Carol A., Laskin, Daniel M., Lauvau, Gregoire, Lee, Tzielan C., Leverenz, David L., Loeser, Richard F., Lozada, Carlos J., Luke, Ofure, Lundberg, Ingrid E., Luqmani, Raashid, Luyten, Frank P., Mader, Reuven, Magee, Conor, Maksymowych, Walter P., Manger, Bernhard, Markenson, Joseph A., Martin, Scott David, Matteson, Eric L., Maxwell, Lara, McCarthy, Katharine, McInnes, Iain B., Merkel, Peter A., Mikuls, Ted R., Miller, Mark S., Misra, Devyani, Mobasheri, Ali, Moder, Kevin G., Monach, Paul A., Montgomery, Anna, Moulton, Vaishali R., Mulders-Manders, Catharina M., Muniz, Luciana Ribeiro, Murphy, Louise B., Nagaraju, Kanneboyina, Nasser, Rani, Nelson, Amanda E., Neogi, Tuhina, Nigrovic, Peter A., O’Dell, James R., Ogdie, Alexis, Østergaard, Mikkel, Paley, Michael A., Panush, Richard S., Peng, Stanford L., Perlman, Harris, Pillai, Shiv, Pillinger, Michael H., Polston, Gregory R., Porcelli, Steven A., Price, Mark D., Pulles, Astrid E., Raza, Karim, Reddy, Virginia, Reed, Ann M., Reveille, John D., Rhee, Rennie L., Ritchlin, Christopher T., Robinson, Angela B., Rosen, Antony, Rosenbaum, James T., Rosenberg, Andrew E., Ruderman, Eric M., Saag, Kenneth G., Salmon, Jane E., Sammaritano, Lisa R., Samuels, Jonathan, Sandborg, Christy I., Sangeorzan, Adam P., Santora, Arthur C., II, Sattui, Sebastian E., Sawalha, Amr H., Saxena, Amit, Saxena, Mansi, Scanzello, Carla R., Schett, Georg, Semb, Anne Grete, Shah, Ami A., Shah, Binita, Sharpley, Faye A., Sikora, Keith A., Simon, Anna, Siraj, Dawd S., Sorkin, Linda S., St. Clair, E. William, Stamp, Lisa K., Stone, John H., Strowd, Lindsay C., Suarez-Fueyo, Abel, Svensson, Camilla I., Sweiss, Nadera J., Swigart, Carrie R., Szekanecz, Zoltán, Tait, Stephen, Tanner, Stacy, Taylor, Peter C., Taylor, William J., Terkeltaub, Robert, Theofilopoulos, Argyrios N., Thornhill, Thomas S., Toprover, Michael, Torok, Kathryn S., Toth, Michael J., Townsend, Michael J., Tozman, Elaine C., Trouw, Leendert A., Tsokos, George C., Tugwell, Peter, Vabret, Nicolas, van der Goes, Marlies C., van der Linden, Sjef, van der Meer, Jos W.M., van Laar, Jacob M., Van Mater, Heather, van Vollenhoven, Ronald F., van Vulpen, Lize F.D., Varga, John, Vasquez, Raul A., Veale, Douglas J., Wakefield, Richard J., Wallace, Mark S., Wang, Ruoning, Wang, Tingting, Werth, Victoria P., Wigley, Fredrick M., Winter, Deborah R., Wofsy, David, Wong, Cyrus C., Yokoyama, Wayne M., Zamore, Richard, Zayat, Ahmed S., Zou, Yong-Rui, and Zurier, Robert B.

Published
2021
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35. Can DNA methylation patterns be used as predictive biomarkers for chemotherapy response in osteosarcoma?

Author

Mukherjee, Sarbajit, primary, Jeffries, Matlock Arizona, additional, Rivas, Alexander, additional, Malik, Reema, additional, Ibrahimi, Sami, additional, Fung, Kar-Ming, additional, White, Jeremy, additional, Meyer, William H., additional, Vesely, Sara, additional, Barkauskas, Donald A., additional, Hall, David, additional, and Cherry, Mohamad Ali, additional

Published
2018
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40. Variants within MECP2, a key transcriptional regulator, are associated with increased susceptibility to lupus and differential gene expression in lupus patients

Author

Webb, Ryan, Wren, Jonathan D, Jeffries, Matlock, Kelly, Jennifer A, Kaufman, Kenneth M, Tang, Yuhong, Frank, Mark Barton, Merrill, Joan, Alarcón-Riquelme, Marta E, James, Judith A, Vyse, Timothy J, Moser, Kathy L, Gilkeson, Gary S, Harley, John B, and Sawalha, Amr H

Subjects
Male, B-Lymphocytes, Methyl-CpG-Binding Protein 2, Genetic Variation, Polymorphism, Single Nucleotide, Article, White People, Epigenesis, Genetic, Cohort Studies, Phenotype, Gene Frequency, Haplotypes, Risk Factors, Humans, Lupus Erythematosus, Systemic, Female, Genetic Predisposition to Disease, Cells, Cultured
Abstract

Both genetic and epigenetic factors play an important role in the pathogenesis of lupus. The aim of this study was to examine methyl-CpG-binding protein 2 gene (MECP2) polymorphisms in a large cohort of patients with lupus and control subjects, and to determine the functional consequences of the lupus-associated MECP2 haplotype.We genotyped 18 single-nucleotide polymorphisms within MECP2, located on chromosome Xq28, in a large cohort of patients with lupus and control subjects of European descent. We studied the functional effects of the lupus-associated MECP2 haplotype by determining gene expression profiles in B cell lines in female lupus patients with and those without the lupus-associated MECP2 risk haplotype.We confirmed, replicated, and extended the genetic association between lupus and genetic markers within MECP2 in a large independent cohort of lupus patients and control subjects of European descent (odds ratio 1.35, P = 6.65 x 10(-11)). MECP2 is a dichotomous transcription regulator that either activates or represses gene expression. We identified 128 genes that are differentially expressed in lupus patients with the disease-associated MECP2 haplotype; most ( approximately 81%) were up-regulated. Genes that were up-regulated had significantly more CpG islands in their promoter regions compared with genes that were down-regulated. Gene ontology analysis using the differentially expressed genes revealed significant association with epigenetic regulatory mechanisms, suggesting that these genes are targets for MECP2 regulation in B cells. Furthermore, at least 13 of the 104 up-regulated genes are regulated by interferon. The disease-risk MECP2 haplotype was associated with increased expression of the MECP2 transcription coactivator CREB1 and decreased expression of the corepressor histone deacetylase 1.Polymorphism in the MECP2 locus is associated with lupus and, at least in part, contributes to the interferon signature observed in lupus patients.

Published
2009

48. Variants withinMECP2, a key transcription regulator, are associated with increased susceptibility to lupus and differential gene expression in patients with systemic lupus erythematosus

Author

Webb, Ryan, primary, Wren, Jonathan D., additional, Jeffries, Matlock, additional, Kelly, Jennifer A., additional, Kaufman, Kenneth M., additional, Tang, Yuhong, additional, Frank, Mark Barton, additional, Merrill, Joan, additional, Kimberly, Robert P., additional, Edberg, Jeffrey C., additional, Ramsey-Goldman, Rosalind, additional, Petri, Michelle, additional, Reveille, John D., additional, Alarcón, Graciela S., additional, Vilá, Luis M., additional, Alarcón-Riquelme, Marta E., additional, James, Judith A., additional, Vyse, Timothy J., additional, Moser, Kathy L., additional, Gaffney, Patrick M., additional, Gilkeson, Gary S., additional, Harley, John B., additional, and Sawalha, Amr H., additional

Published
2009
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