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3. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

Author

Patsopoulos, Nikolaos A, Baranzini, Sergio E, Santaniello, Adam, Shoostari, Parisa, Cotsapas, Chris, Wong, Garrett, Beecham, Ashley H, James, Tojo, Replogle, Joseph, Vlachos, Ioannis S, McCabe, Cristin, Pers, Tune H, Brandes, Aaron, White, Charles, Keenan, Brendan, Cimpean, Maria, Winn, Phoebe, Panteliadis, Ioannis-Pavlos, Robbins, Allison, Andlauer, Till FM, Zarzycki, Onigiusz, Dubois, Bénédicte, Goris, An, Søndergaard, Helle Bach, Sellebjerg, Finn, Sorensen, Per Soelberg, Ullum, Henrik, Thørner, Lise Wegner, Saarela, Janna, Cournu-Rebeix, Isabelle, Damotte, Vincent, Fontaine, Bertrand, Guillot-Noel, Lena, Lathrop, Mark, Vukusic, Sandra, Berthele, Achim, Pongratz, Viola, Buck, Dorothea, Gasperi, Christiane, Graetz, Christiane, Grummel, Verena, Hemmer, Bernhard, Hoshi, Muni, Knier, Benjamin, Korn, Thomas, Lill, Christina M, Luessi, Felix, Mühlau, Mark, Zipp, Frauke, Dardiotis, Efthimios, Agliardi, Cristina, Amoroso, Antonio, Barizzone, Nadia, Benedetti, Maria D, Bernardinelli, Luisa, Cavalla, Paola, Clarelli, Ferdinando, Comi, Giancarlo, Cusi, Daniele, Esposito, Federica, Ferrè, Laura, Galimberti, Daniela, Guaschino, Clara, Leone, Maurizio A, Martinelli, Vittorio, Moiola, Lucia, Salvetti, Marco, Sorosina, Melissa, Vecchio, Domizia, Zauli, Andrea, Santoro, Silvia, Mancini, Nicasio, Zuccalà, Miriam, Mescheriakova, Julia, van Duijn, Cornelia, Bos, Steffan D, Celius, Elisabeth G, Spurkland, Anne, Comabella, Manuel, Montalban, Xavier, Alfredsson, Lars, Bomfim, Izaura L, Gomez-Cabrero, David, Hillert, Jan, Jagodic, Maja, Lindén, Magdalena, Piehl, Fredrik, Jelčić, Ilijas, Martin, Roland, Sospedra, Mirela, Baker, Amie, Ban, Maria, Hawkins, Clive, Hysi, Pirro, Kalra, Seema, Karpe, Fredrik, Khadake, Jyoti, Lachance, Genevieve, Molyneux, Paul, and Neville, Matthew

Subjects
Neurosciences, Brain Disorders, Multiple Sclerosis, Human Genome, Autoimmune Disease, Clinical Research, Genetics, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Neurological, Case-Control Studies, Cell Cycle Proteins, Chromosome Mapping, Chromosomes, Human, X, GTPase-Activating Proteins, Gene Frequency, Genetic Loci, Genome-Wide Association Study, Genomics, Humans, Inheritance Patterns, Major Histocompatibility Complex, Microglia, Polymorphism, Single Nucleotide, Quantitative Trait Loci, RNA-Seq, Transcriptome, International Multiple Sclerosis Genetics Consortium, General Science & Technology
Abstract

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.

Published
2019

6. Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial

Author

Muñoz, Daniel Julio, Amor, Jorge David, Bocchiardo, Carolina, Danielle, Julieta Iourno, Laffue, Alfredo, Obregon, Carolina Daniela Diaz, Paez, Maria Fernanda, Perez, Roberto Martin, Rocchi, Viviana Ana Maria, Teijeiro, Loreley Deborah, Gómez, Jesica, Villa, Andres Maria, Aguirre, Florencia, Fernández, Victoria Carla, Goicoechea, Ramon F., Melamud, Luciana, Stillman, Ana, de Virgiliis, Mariana, Cassara, Fatima Pagani, Cordoba, Marta, Gutierrez, Maria Teresa, Ingolotti, Mariana, Larripa, Natalia, Lupinacci, Anahi, Arroyo, Josefina, Romano, Alejandra, Torres, Mariana Foa, Ballario, Carlos Héctor, Chiesa, Ana Elisa, Gómez, Hernán Gustavo, Lattini, Hernán Gabriel, Mainella, Carolina Natalia, Bolner, Gisel Edith, Eschoyez, María Soledad, Broadley, Simon Andrew, Heshmat, Saman, Sabet, Arman, Swayne, Andrew, Freeman, Susan, Sanchez, Sofia Jimenez, Shuey, Neil, Dalic, Linda, French, Ann, Kuma, Guru, Laing, Joshua, Law, Lai Yin, MacIntyre, Jennifer, Neal, Andrew, Plummer, Christopher, Ramachandran, Prashanth, Sedal, Leslie, Wilson, Ian, Winkel, Antony, Zhang, Wenwen, Chen, Tina, Watts, Rani, Barnett, Michael, Barton, Joshua, Beadnall, Heidi, Garber, Justin, Hardy, Todd Andrew, Trewin, Benjamin, Taha, Marinda, Walters, Deleni, Sieger, Federico Arturo Silva, Alfonso, Nhora Patricia Ruiz, Camacho, Anna Maria Pinzon, Moreno, Alexander Pabón, Prad, Jorge Armando Castellanos, Rueda, Adriana Paola Duarte, Castillo, Tatiana, Gonzalez, Karol Melissa Castillo, Pico, Martha Yolanda Moreno, Castill, Judith, Habek, Mario, Adamec, Ivan, Barun, Barbara, Crnosija, Luka, Gabelic, Tereza, Nytrova, Petra, Krasulova, Eva, Pavlickova, Jana, Tyblova, Michaela, Zubkova, Jana, Petersen, Thor, Dale, Gro Helen, Rasmussen, Peter Vestergaard, Stilund, Morten, Svendsen, Kristina Bacher, Brandt, Vivi, Collongues, Nicolas, Fleury, Marie-Celine, Kremer, Laurent, Bendele, Sandrine, Neff, Valérie, Diem, Ricarda, Platten, Michael, Berberich, Anne, Jansen, Jonabelle, Jaschoneck, Hannah, Wildemann, Brigitte, Aures, Ursula, Brandenburger, Tanja, Haut, Tanja, Fernández, Maria-Lourdes Treceno, Aly, Lilian, Brinkhoff, Kirsten, Buck, Dorothea, Golkowski, Daniel, Hermisson, Mirjam, Hoshi, Muna-Miriam, Kaminski, Miriam, Kowarik, Markus Christian, Kronsbein, Helena, Lehmann-Horn, Klaus, Pongratz, Viola Maria, Schweiker, Andreas, Leddy, Lisa-Ann, Mueller, Silvia, Obergfell, Kim, Wanka, Marion, Zettl, Uwe Klaus, Klinke, Jan, Loebermann, Micha, Meister, Stefanie, Rimmele, Florian, Winkelmann, Alexander, Schroeder, Ina, Lau, Alexander Yuk-Lun, Au, Lisa Wing-Chi, Fan, Florence Sin-Ying, Ip, Vincent Hing-Lung, Ma, Karen Ka-Yan, Ma, Sze-Ho, Mok, Vincent Chung-Tong, Au, Cheryl Chung-Kwan, Kwan, Pauline Wing-Lam, Patti, Francesco, Caramma, Andrea Salvatore, Chisari, Clara Grazia, Fermo, Salvatore Lo, Messina, Silvia, Projetto, Maria, Caserta, Cinzia, Filla, Alessandro, Costabile, Teresa, Pane, Chiara, Sacca, Francesco, Marsili, Angela, Puorro, Giorgia, Bergamaschi, Roberto, Berra, Eliana, Mallucci, Giulia, Fattore, Cinzia, Gasperini, Claudio, Galgani, Simonetta, Haggiag, Shalom, Ruggieri, Serena, Vento, Claudio, Quartuccio, Esmeralda Maria, Pozzilli, Carlo, Barletta, Valeria Teresa, Borriello, Giovanna, De Giglio, Laura, Marinelli, Fabiana, Tasillo, Miriam, Amadori, Alessandra, Fischetti, Mariano, Gurreri, Flavia, Mori, Masahiro, Masuda, Hiroki, Ohtani, Ryohei, Sekiguchi, Yukari, Uchida, Tomohiko, Uzawa, Akiyuki, Ito, Hiromi, Kabasawa, Emi, Kaneko, Yoko, Matsushita, Takuya, Matsuse, Dai, Murai, Hiroyuki, Hayashi, Shintaro, Masak, Katsuhisa, Ogata, Hidenori, Shinoda, Koji, Uehara, Taira, Watanabe, Mitsuru, Yamaguchi, Hiroo, Yamasaki, Ryo, Yonekawa, Tomomi, Jingu, Maki, Nagano, Makiko, Nakamura, Yumiko, Sano, Yoshiko, Araki, Manabu, Lin, Youwei, Mori, Madoka, Mukai, Yohei, Sano, Terunori, Sato, Wakiro, Gogun, Naoya, Maeda, Yuriko, Nishimoto, Asami, Tsukamoto, Sachiko, Yanagi, Ritsuko, Saida, Takahiko, Nakamura, Shinichi, Nasu, Tetsuya, Saida, Kyoko, Shikata, Yuko, Kodani, Yoshimi, Saeki, Megumi, Sawada, Yukako, Yoshikawa, Hiroo, Kimura, Takashi, Nishi, Masamitsu, Sakamoto, Shun, Ukon, Shinichiro, Watanabe, Shohei, Ebisuya, Saori, Kimura, Nami, Matsuura, Manami, Morisaki, Yukie, Muroi, Yoshiko, Onishi, Kuniko, Oshima, Ikuko, Washino, Yuki, Yamashita, Tomomi, Misu, Tatsuro, Kaneko, Kimihiko, Kato, Masaaki, Kuroda, Hiroshi, Kurosawa, Kazuhiro, Nishiyama, Shuhei, Ono, Hirohiko, Takai, Yoshiki, Abe, Keiko, Hoshi, Hitomi, Jinushi, Mari, Oyama, Azusa, Sakuma, Motonari, Sawada, Yuko, Ishibashi, Satoru, Yokota, Takanori, Nishida, Yoichiro, Ozaki, Kokoro, Sanjo, Nobuo, Sato, Nozomu, Denno, Fuki, Hiraki, Haruko, Matsubara, Yumi, Kanda, Takashi, Abe, Masaaki, Honda, Masaya, Kawai, Motoharu, Koga, Michiaki, Maeda, Toshihiko, Ogasawara, Junichi, Omoto, Masatoshi, Sano, Yasuteru, Sato, Ryota, Shimizu, Fumitaka, Arima, Hideki, Fukui, Sachie, Ishikawa, Yoshiko, Koyama, Tomoko, Shimose, Shigemi, Shinozaki, Hirokazu, Watanabe, Masanori, Yasuda, Sachi, Yoshiwaka, Chieko, Adenan, Suffian, Aris, Mohd Azman M, Mawardi, Ahmad Shahir bin, Adnan, Muhammad Al Hafiz, Munusamy, Nanthini, Razali, Siti Nur Omaira, Somasundram, Punitha, Hyun, Jae Won, Jeong, In Hye, Kim, Su-Hyun, Shin, Hyun-June, Yoo, Ji Sung, Jang, HyunMin, Joung, AeRan, Kim, Byung-Jo, Baek, Seol-Hee, Kim, Jung Bin, Kim, Yoo Hwan, Koo, Yong Seo, Lee, Chan Nyoung, Seok, Hung Youl, Hwang, Jinhee, Kim, Sung Min, Ahn, So Hyun, Choi, Kyomin, Choi, Seok-Jin, Kim, Jun-Soon, Kwon, Young Nam, Shin, Je-Young, Kwon, Hyeonju, Kim, Byoung Joon, Cho, Eun Bin, Cho, Hye-Jin, Choi, Misong, Kim, DongSun, Kim, Ju Hyeon, Ki, SeungJu, Lee, Hye Lim, Lee, Kwang-Ho, Min, Ju-Hong, Park, Ji-Hyung, Seok, Jinmyoung, Choi, Eunhwa, Park, Sang Ae, Kim, Seung Min, Jeong, Ha-Neul, Jeongbin, Bong, Jung, Jin Woo, Kim, Seung Woo, Kim, Yool-hee, Lee, Hyung Seok, Shin, Ha Young, Jung, Yeon, Kim, Min Jung, Lee, Nou Ri, Shin, MiJu, Khabirov, Farit A, Averyanova, Lyudmila, Babicheva, Natalya, Granatov, Eugenii, Kazarov, Sergey, Khaybullin, Timur, Rogozhin, Alexander, Pokhabov, Dmitry V, Abramov, Vladislav, Amelina, Anastasia, Nesteroca, Yulia, Bozhenkina, Tatyana, Boyko, Aleksey N, Demyan, Elena G, Khoroshilova, Inessa, Melnikov, Mikhail, Popova, Ekaterina V, Sharanova, Svetlana N, Shchur, Sergey G, Sazonov, Denis V, Babenko, Larisa, Bayandina, Elena, Yarmoschuk, Asya, Baliazin, Victor A, Baliazina, Elena, Budaeva, Elena, Chernikova, Irina, Goncharova, Zoya, Krasnov, Vladimir, Myatleva, Marina, Rodionova, Olga V., Samulyzhko, Iuliana, Timofeeva, Alla A., Duran, Sabas Boyero, Bilbao, Maria Mar Mendibe, Cuervo, Irene Diaz, Domingo, Jose Maria Losada, Eizaguirre, Amaia Gonzalez, Llona, Jose Eulalio Barcena, Moyano, Roberto Valverde, Bahamonde, Carmen, Lopez, Fernando Sanchez, Morales, Raquel Pinar, Morales, Eduardo Agüera, Roman, Carmen Bahamonde, Sepulveda, Juan Jose Ochoa, Valero, Maria del Carmen Blanco, Viña, Nazaret Pelaez, Gavilan, Cristina Conde, Sanchez, Ana Maria Jover, Bedmar, Sara Vila, Garcia, Nuria Gonzalez, Garcia, Aida Orviz, Gonzalez-Suarez, Ines, Guillamon, Elena Miñano, Kawiorski, Miguel, Schulz, Elena Guerra, Alonso, Alba Garcia, Perez, Francisco Jesus Lopez, Sarmiento, Marta Palacios, Ayuso, Guillermo Izquierdo, Mascarell, Guillermo Navarro, Camino, Cristina Paramo, Garcia, Asuncion Varas, Mendoza, Yaiza Montserrat, Muñoz, Veronica Ines Vargas, Tonda, Patricia Torres, Tsai, Ching-Piao, Yin, Jiu-Haw, Chen, Mei-Jung, Li, Shan-Ni, Wang, Fei-Ti, Srisuwannanukorn, Suwat, Boonmongkol, Thanatat, Borisutbuathip, Duangporn, Singwicha, Duangkamol, Siritanan, Krittika, Thearapati, Chidchanoke, Sornda, Kwanmuang, Apiwattanakul, Metha, Aungsumart, Saharat, Suanprasert, Narupat, Suksuchano, Kaona, Parkinsee, Nittaya, Kulkantrakorn, Kongkiat, Lolekha, Praween, Potigumjon, Artit, Sukphulloprat, Puchit, Suksasunee, Dararat, Komaratat, Chankawee, Luangtong, Sunattana, Arayawichanont, Arkhom, Konpan, Phanpaphon, Riablershirun, Nathapol, Wiroteurairuang, Thaddao, Jantaweesirirat, Panadda, Kurne, Aslı, Erkent, Irem, Kurt, Ebru Bekircan, Saylam, Ezgi, Caliskan, Yagmur, Orsel, Gulsah, Celik, Yahya, Celebi, Canan, Tekatas, Aslan, Banbal, Tugce, Demir, Gulsen Akman, Altunrende, Burcu, Matur, Zeliha, Topcular, Baris, Elmas, Tules, Gulo, Aysenur, Ozdemir, Selin, Ozkoklesen, Cansu, Ozturk, Mahinur, Yanik, Mertkan, Yildirim, Elif, Tutuncu, Melih, Altintas, Ayse, Cam, Abdulsamet, Elmali, Ayse Deniz, Saip, Sabahattin, Siva, Aksel, Tanrıverdi, Uygur, Uygunoglu, Ugur, Caliskan, Sinem, Gulo, Pinar, Kozig, Esra, Sakiz, Sakine, Sengun, Ihsan Sukru, Idiman, Egemen, Ala, Rahmi Tumay, Arslan, Duygu, Bulut, Utku, Karakaptan, Yasemin, Kaya, Derya, Mehdiyev, Zaur, Balkan, Bengu, Kuku, Berfu, Ozhun, Mujgan, Tuga, Celal, Ugur, Muzeyyen, Efendi, Husnu, Bunul, Sena Destan, Cavus, Hakan, Gorke, Yunus Emre, Kutlu, Ayse, Ozturk, Seda, Sarikaya, Cansu Egilmez, Becerikli, Gulsah, Semiz, Cansu, Tun, Ozlem, Ayer, Sehriban, Onar, Musa Kazim, Ozberk, Mehlika Berra, Sen, Sedat, Cavdar, Tugce Kirbas, Veske, Adife, Boz, Cavit, Altiparmak, Didem, Aydin, Cigdem Ozen, Gazioglu, Sibel, Bekircan, Duygu, Jacob, Anu, Arndt, Heike, Elsone, Liene, Hamid, Shahd Hassan Mahmoud, Whittam, Daniel Hugh, Wilson, Martin, O'Brien, Imelda, Leite, Maria Isabel da Silva, Cruz, Pedro Maria Rodriguez, Jenkins, Damian Robert, Tackley, George, Cavey, Ana, Everett, Rosie, Hodder, Joy, Koelewyn, Abigail, Mowry, Ellen, Royal, Walter, III, Shin, Robert, Bever, Christopher, Jr, Harrison, Daniel, Rus, Horea, Zheng, Wei, Callison, Karen, Naunton, Kerry, Frishberg, Benjamin M, Blumenfeld, Andrew M, Inocelda, Andrew, Korabathina, Kalyani, Lobatz, Michael, Mortin, Melissa M, Oh, Irene J, Rosenberg, Jay H, Sadoff, Mark, Sahagian, Gregory A, Wang, Anchi, Camberos, Yasmin, Sanchez, Guadalupe, Soto, Estela, Nicholas, Jacqueline A, Boster, Aaron, Eubank, Geoffrey, Groezinger, Katy, Lauf, Meghan, Okai, Annette F, Hasan, Rashedul, Khoury, Chaouki, Stokes, Victoria, Clardy, Stacey, Cortez, Melissa, Greenlee, John, Rose, John, Soldan, Mateo Paz, Emett, Amanda, Esquibel, Lawanda, Fagatele, Lilly, Wong, Ka-Ho, Stevens, James C, Banas, Thomas M, Bultemeyer, Marlene C, Haller, Andrea, Manalo, Natalie, Aeschliman, Keri, Kocks, Debi, Racke, Michael, Boster, Aaron Lee, Bowman, Michelle, Imitola, Jaime, Kisanuki, Yasushi, Green, Misty, Scarberry, Stephanie, Lynch, Sharon G, Anderson, Heather S, Gronseth, Gary S, Hammond, Nancy E, Jassam, Yasir N, Mittal, Manoj K, Nashatizadeh, Muhammed M, Levine, Nicholas, Schmidt, Lisa, Sibley, Jill, Whitley, Vonda, Winkley, James, Coleman, Timothy, Cooper, Gregory, Sheffield, Stephanie, Turner, Keri, Galloway, Dana, Tillett, Robert S, Jr, Ganesh, Geeta A, Plato, Brian M, Seifert, Tad D, Godwin, Diana, Lockridge, Deborah, Rammohan, Kottil W, Sheremata, William A, Delgado, Silvia, Gonzalez, Jose, Lizarraga, Alexis, Maldonado, Janice, Ortega, Melissa, Tornes, Leticia, Babcock, Yanet, Cailam, Osmara, Campos, Yesica, Couvertier, Irlisse, Daneri, Bettina, Deni, Jeremy, Hernandez, Jeffrey, Jaramillo, Tatiana, Morris, Tenita, Nobel, Daniel, Oliveira, Anjelis, Richardson, Reshma, Rodriguez, Gloria, Romero, Ana, Sandova, Carlos, Sawant, Ruta, Tueros, Lissett, Zetka, Eric S, Zheng, Chao, Jacobs, Daniel H, Easterling, Constance, Fairbank, Jennifer, Iyengar, Revathi, Klafter, Mark, Lindquist, Justin, Sadek, Ahmed H, Toro, Elizabeth Carmona, Verma, Navin, Castro, Brigith Patino, Sukhraj-Singh, Nadia, Berger, Joseph, Williamson, Eric, Chahin, Salim, Jacobs, Dina, Markowitz, Clyde, Dobbins, Jessica, Mace, Lauren, Martin, Maria, Pinckney, Ashley, Roberts, Amber, Zaydan, Islam, Mitchell, Galen W, Heyman, Rock A, Orie, Ryan L, Suski, Valerie R, Oddis, Kerry, Punjack, Darlene, Flanagan, Eoin, Gadoth, Avi, McKeon, Andrew, Tobin, W Oliver, Zekeridou, Anastasia, Dunlay, Katie, Sagen, Jessica, Carter, Jonathan L, Estephan, Bachir, Goodman, Brent P, Snyder, Charlene R Hoffman, Francone, Andrea, Galasky, Irene, Thomas, Martha, Repovic, Pavle, Bowen, James, Mayadev, Angeli, Qian, Peiqing, Courtney, Yuriko, Lennox, Lauren, Naismith, Robert Thomas, Cross, Anne Haney, Evans, Emily, Longbrake, Erin E, Orchard, Megan E, Wu, Gregory F, Heinrich, Linda, Sommers, Susan, Amjad, Faria, Mitchell, Erika, Mora, Carlos, Schreiber, Bethany, Tornatore, Carlo, Carlson, Alexis, McCarthy, Sacha, Oliver, Alexandria, Palace, Jacqueline, Wingerchuk, Dean M., Fujihara, Kazuo, Berthele, Achim, Oreja-Guevara, Celia, Kim, Ho Jin, Nakashima, Ichiro, Levy, Michael, Terzi, Murat, Totolyan, Natalia, Viswanathan, Shanthi, Wang, Kai-Chen, Pace, Amy, Yountz, Marcus, Miller, Larisa, Armstrong, Róisín, and Pittock, Sean

Published
2021
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10. Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Author

Mitrovič, Mitja, Patsopoulos, Nikolaos A., Beecham, Ashley H., Dankowski, Theresa, Goris, An, Dubois, Bénédicte, D’hooghe, Marie B., Lemmens, Robin, Van Damme, Philip, Søndergaard, Helle Bach, Sellebjerg, Finn, Sorensen, Per Soelberg, Ullum, Henrik, Thørner, Lise W., Werge, Thomas, Saarela, Janna, Cournu-Rebeix, Isabelle, Damotte, Vincent, Fontaine, Bertrand, Guillot-Noel, Lena, Lathrop, Mark, Vukusik, Sandra, Gourraud, Pierre-Antoine, Andlauer, Till F.M., Pongratz, Viola, Buck, Dorothea, Gasperi, Christiane, Bayas, Antonios, Heesen, Christoph, Kümpfel, Tania, Linker, Ralf, Paul, Friedemann, Stangel, Martin, Tackenberg, Björn, Bergh, Florian Then, Warnke, Clemens, Wiendl, Heinz, Wildemann, Brigitte, Zettl, Uwe, Ziemann, Ulf, Tumani, Hayrettin, Gold, Ralf, Grummel, Verena, Hemmer, Bernhard, Knier, Benjamin, Lill, Christina M., Luessi, Felix, Dardiotis, Efthimios, Agliardi, Cristina, Barizzone, Nadia, Mascia, Elisabetta, Bernardinelli, Luisa, Comi, Giancarlo, Cusi, Daniele, Esposito, Federica, Ferrè, Laura, Comi, Cristoforo, Galimberti, Daniela, Leone, Maurizio A., Sorosina, Melissa, Mescheriakova, Julia, Hintzen, Rogier, van Duijn, Cornelia, Teunissen, Charlotte E., Bos, Steffan D., Myhr, Kjell-Morten, Celius, Elisabeth G., Lie, Benedicte A., Spurkland, Anne, Comabella, Manuel, Montalban, Xavier, Alfredsson, Lars, Stridh, Pernilla, Hillert, Jan, Jagodic, Maja, Piehl, Fredrik, Jelčić, Ilijas, Martin, Roland, Sospedra, Mireia, Ban, Maria, Hawkins, Clive, Hysi, Pirro, Kalra, Seema, Karpe, Fredrik, Khadake, Jyoti, Lachance, Genevieve, Neville, Matthew, Santaniello, Adam, Caillier, Stacy J., Calabresi, Peter A., Cree, Bruce A.C., Cross, Anne, Davis, Mary F., Haines, Jonathan L., de Bakker, Paul I.W., Delgado, Silvia, Dembele, Marieme, Edwards, Keith, Fitzgerald, Kathryn C., Hakonarson, Hakon, Konidari, Ioanna, Lathi, Ellen, Manrique, Clara P., Pericak-Vance, Margaret A., Piccio, Laura, Schaefer, Cathy, McCabe, Cristin, Weiner, Howard, Goldstein, Jacqueline, Olsson, Tomas, Hadjigeorgiou, Georgios, Taylor, Bruce, Tajouri, Lotti, Charlesworth, Jac, Booth, David R., Harbo, Hanne F., Ivinson, Adrian J., Hauser, Stephen L., Compston, Alastair, Stewart, Graeme, Zipp, Frauke, Barcellos, Lisa F., Baranzini, Sergio E., Martinelli-Boneschi, Filippo, D’Alfonso, Sandra, Ziegler, Andreas, Oturai, Annette, McCauley, Jacob L., Sawcer, Stephen J., Oksenberg, Jorge R., De Jager, Philip L., Kockum, Ingrid, Hafler, David A., and Cotsapas, Chris

Published
2018
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13. Prognostic value of spinal cord lesion measures in early relapsing-remitting multiple sclerosis

Author

Lauerer, Markus, primary, McGinnis, Julian, additional, Bussas, Matthias, additional, El Husseini, Malek, additional, Pongratz, Viola, additional, Engl, Christina, additional, Wuschek, Alexander, additional, Berthele, Achim, additional, Riederer, Isabelle, additional, Kirschke, Jan S, additional, Zimmer, Claus, additional, Hemmer, Bernhard, additional, and Mühlau, Mark, additional

Published
2023
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16. Early spinal cord pseudoatrophy in interferon‐beta‐treated multiple sclerosis

Author

Matusche, Britta, primary, Litvin, Ludmila, additional, Schneider, Ruth, additional, Bellenberg, Barbara, additional, Mühlau, Mark, additional, Pongratz, Viola, additional, Berthele, Achim, additional, Groppa, Sergiu, additional, Muthuraman, Muthuraman, additional, Zipp, Frauke, additional, Paul, Friedemann, additional, Wiendl, Heinz, additional, Meuth, Sven G., additional, Sämann, Philipp, additional, Weber, Frank, additional, Linker, Ralf A., additional, Kümpfel, Tania, additional, Gold, Ralf, additional, and Lukas, Carsten, additional

Published
2022
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17. Somatosensory evoked potentials and magnetic resonance imaging of the central nervous system in early multiple sclerosis

Author

Wuschek, Alexander, primary, Bussas, Matthias, additional, El Husseini, Malek, additional, Harabacz, Laura, additional, Pineker, Viktor, additional, Pongratz, Viola, additional, Berthele, Achim, additional, Riederer, Isabelle, additional, Zimmer, Claus, additional, Hemmer, Bernhard, additional, Kirschke, Jan S., additional, and Mühlau, Mark, additional

Published
2022
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18. Early spinal cord pseudoatrophy in interferon‐beta‐treated multiple sclerosis.

Author

Matusche, Britta, Litvin, Ludmila, Schneider, Ruth, Bellenberg, Barbara, Mühlau, Mark, Pongratz, Viola, Berthele, Achim, Groppa, Sergiu, Muthuraman, Muthuraman, Zipp, Frauke, Paul, Friedemann, Wiendl, Heinz, Meuth, Sven G., Sämann, Philipp, Weber, Frank, Linker, Ralf A., Kümpfel, Tania, Gold, Ralf, and Lukas, Carsten

Subjects
SPINAL cord, MULTIPLE sclerosis, CERVICAL cord, CEREBRAL atrophy, MAGNETIC resonance imaging
Abstract

Background and purpose: Brain pseudoatrophy has been shown to play a pivotal role in the interpretation of brain atrophy measures during the first year of disease‐modifying therapy in multiple sclerosis. Whether pseudoatrophy also affects the spinal cord remains unclear. The aim of this study was to analyze the extent of pseudoatrophy in the upper spinal cord during the first 2 years after therapy initiation and compare this to the brain. Methods: A total of 129 patients from a prospective longitudinal multicentric national cohort study for whom magnetic resonance imaging scans at baseline, 12 months, and 24 months were available were selected for brain and spinal cord volume quantification. Annual percentage brain volume and cord area change were calculated using SIENA (Structural Image Evaluation of Normalized Atrophy) and NeuroQLab, respectively. Linear mixed model analyses were performed to compare patients on interferon‐beta therapy (n = 84) and untreated patients (n = 45). Results: Patients treated with interferon‐beta demonstrated accelerated annual percentage brain volume and cervical cord area change in the first year after treatment initiation, whereas atrophy rates stabilized to a similar and not significantly different level compared to untreated patients during the second year. Conclusions: These results suggest that pseudoatrophy occurs not only in the brain, but also in the spinal cord during the first year of interferon‐beta treatment. [ABSTRACT FROM AUTHOR]

Published
2023
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19. Percentage brain volume change in multiple sclerosis mainly reflects white matter and cortical volume.

Author

Lauerer, Markus, Bussas, Matthias, Pongratz, Viola, Berthele, Achim, Kirschke, Jan S, Wiestler, Benedikt, Zimmer, Claus, Hemmer, Bernhard, and Mühlau, Mark

Subjects
WHITE matter (Nerve tissue), MULTIPLE sclerosis, GRAY matter (Nerve tissue), MAGNETIC resonance imaging, CEREBRAL atrophy
Abstract

Brain atrophy in multiple sclerosis (MS), as measured by percentage brain volume change (PBVC) from brain magnetic resonance imaging (MRI), has been established as an outcome parameter in clinical trials. It is unknown to what extent volume changes within different brain tissue compartments contribute to PBVC. We analyzed pairs of MRI scans (at least 6 months apart) in 600 patients with relapsing–remitting MS. Multiple regression revealed that PBVC mainly reflects volume loss of white and cortical gray matter, while deep gray matter and white matter lesions were less represented. Our findings aid the interpretation of PBVC changes in MS. [ABSTRACT FROM AUTHOR]

Published
2023
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20. Gray matter atrophy in relapsing-remitting multiple sclerosis is associated with white matter lesions in connecting fibers

Author

Bussas, Matthias, primary, Grahl, Sophia, additional, Pongratz, Viola, additional, Berthele, Achim, additional, Gasperi, Christiane, additional, Andlauer, Till, additional, Gaser, Christian, additional, Kirschke, Jan S, additional, Wiestler, Benedikt, additional, Zimmer, Claus, additional, Hemmer, Bernhard, additional, and Mühlau, Mark, additional

Published
2021
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21. Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial

Author

Palace, Jacqueline, primary, Wingerchuk, Dean M., additional, Fujihara, Kazuo, additional, Berthele, Achim, additional, Oreja-Guevara, Celia, additional, Kim, Ho Jin, additional, Nakashima, Ichiro, additional, Levy, Michael, additional, Terzi, Murat, additional, Totolyan, Natalia, additional, Viswanathan, Shanthi, additional, Wang, Kai-Chen, additional, Pace, Amy, additional, Yountz, Marcus, additional, Miller, Larisa, additional, Armstrong, Róisín, additional, Pittock, Sean, additional, Muñoz, Daniel Julio, additional, Amor, Jorge David, additional, Bocchiardo, Carolina, additional, Danielle, Julieta Iourno, additional, Laffue, Alfredo, additional, Obregon, Carolina Daniela Diaz, additional, Paez, Maria Fernanda, additional, Perez, Roberto Martin, additional, Rocchi, Viviana Ana Maria, additional, Teijeiro, Loreley Deborah, additional, Gómez, Jesica, additional, Villa, Andres Maria, additional, Aguirre, Florencia, additional, Fernández, Victoria Carla, additional, Goicoechea, Ramon F., additional, Melamud, Luciana, additional, Stillman, Ana, additional, de Virgiliis, Mariana, additional, Cassara, Fatima Pagani, additional, Cordoba, Marta, additional, Gutierrez, Maria Teresa, additional, Ingolotti, Mariana, additional, Larripa, Natalia, additional, Lupinacci, Anahi, additional, Arroyo, Josefina, additional, Romano, Alejandra, additional, Torres, Mariana Foa, additional, Ballario, Carlos Héctor, additional, Chiesa, Ana Elisa, additional, Gómez, Hernán Gustavo, additional, Lattini, Hernán Gabriel, additional, Mainella, Carolina Natalia, additional, Bolner, Gisel Edith, additional, Eschoyez, María Soledad, additional, Broadley, Simon Andrew, additional, Heshmat, Saman, additional, Sabet, Arman, additional, Swayne, Andrew, additional, Freeman, Susan, additional, Sanchez, Sofia Jimenez, additional, Shuey, Neil, additional, Dalic, Linda, additional, French, Ann, additional, Kuma, Guru, additional, Laing, Joshua, additional, Law, Lai Yin, additional, MacIntyre, Jennifer, additional, Neal, Andrew, additional, Plummer, Christopher, additional, Ramachandran, Prashanth, additional, Sedal, Leslie, additional, Wilson, Ian, additional, Winkel, Antony, additional, Zhang, Wenwen, additional, Chen, Tina, additional, Watts, Rani, additional, Barnett, Michael, additional, Barton, Joshua, additional, Beadnall, Heidi, additional, Garber, Justin, additional, Hardy, Todd Andrew, additional, Trewin, Benjamin, additional, Taha, Marinda, additional, Walters, Deleni, additional, Sieger, Federico Arturo Silva, additional, Alfonso, Nhora Patricia Ruiz, additional, Camacho, Anna Maria Pinzon, additional, Moreno, Alexander Pabón, additional, Prad, Jorge Armando Castellanos, additional, Rueda, Adriana Paola Duarte, additional, Castillo, Tatiana, additional, Gonzalez, Karol Melissa Castillo, additional, Pico, Martha Yolanda Moreno, additional, Castill, Judith, additional, Habek, Mario, additional, Adamec, Ivan, additional, Barun, Barbara, additional, Crnosija, Luka, additional, Gabelic, Tereza, additional, Nytrova, Petra, additional, Krasulova, Eva, additional, Pavlickova, Jana, additional, Tyblova, Michaela, additional, Zubkova, Jana, additional, Petersen, Thor, additional, Dale, Gro Helen, additional, Rasmussen, Peter Vestergaard, additional, Stilund, Morten, additional, Svendsen, Kristina Bacher, additional, Brandt, Vivi, additional, Collongues, Nicolas, additional, Fleury, Marie-Celine, additional, Kremer, Laurent, additional, Bendele, Sandrine, additional, Neff, Valérie, additional, Diem, Ricarda, additional, Platten, Michael, additional, Berberich, Anne, additional, Jansen, Jonabelle, additional, Jaschoneck, Hannah, additional, Wildemann, Brigitte, additional, Aures, Ursula, additional, Brandenburger, Tanja, additional, Haut, Tanja, additional, Fernández, Maria-Lourdes Treceno, additional, Aly, Lilian, additional, Brinkhoff, Kirsten, additional, Buck, Dorothea, additional, Golkowski, Daniel, additional, Hermisson, Mirjam, additional, Hoshi, Muna-Miriam, additional, Kaminski, Miriam, additional, Kowarik, Markus Christian, additional, Kronsbein, Helena, additional, Lehmann-Horn, Klaus, additional, Pongratz, Viola Maria, additional, Schweiker, Andreas, additional, Leddy, Lisa-Ann, additional, Mueller, Silvia, additional, Obergfell, Kim, additional, Wanka, Marion, additional, Zettl, Uwe Klaus, additional, Klinke, Jan, additional, Loebermann, Micha, additional, Meister, Stefanie, additional, Rimmele, Florian, additional, Winkelmann, Alexander, additional, Schroeder, Ina, additional, Lau, Alexander Yuk-Lun, additional, Au, Lisa Wing-Chi, additional, Fan, Florence Sin-Ying, additional, Ip, Vincent Hing-Lung, additional, Ma, Karen Ka-Yan, additional, Ma, Sze-Ho, additional, Mok, Vincent Chung-Tong, additional, Au, Cheryl Chung-Kwan, additional, Kwan, Pauline Wing-Lam, additional, Patti, Francesco, additional, Caramma, Andrea Salvatore, additional, Chisari, Clara Grazia, additional, Fermo, Salvatore Lo, additional, Messina, Silvia, additional, Projetto, Maria, additional, Caserta, Cinzia, additional, Filla, Alessandro, additional, Costabile, Teresa, additional, Pane, Chiara, additional, Sacca, Francesco, additional, Marsili, Angela, additional, Puorro, Giorgia, additional, Bergamaschi, Roberto, additional, Berra, Eliana, additional, Mallucci, Giulia, additional, Fattore, Cinzia, additional, Gasperini, Claudio, additional, Galgani, Simonetta, additional, Haggiag, Shalom, additional, Ruggieri, Serena, additional, Vento, Claudio, additional, Quartuccio, Esmeralda Maria, additional, Pozzilli, Carlo, additional, Barletta, Valeria Teresa, additional, Borriello, Giovanna, additional, De Giglio, Laura, additional, Marinelli, Fabiana, additional, Tasillo, Miriam, additional, Amadori, Alessandra, additional, Fischetti, Mariano, additional, Gurreri, Flavia, additional, Mori, Masahiro, additional, Masuda, Hiroki, additional, Ohtani, Ryohei, additional, Sekiguchi, Yukari, additional, Uchida, Tomohiko, additional, Uzawa, Akiyuki, additional, Ito, Hiromi, additional, Kabasawa, Emi, additional, Kaneko, Yoko, additional, Matsushita, Takuya, additional, Matsuse, Dai, additional, Murai, Hiroyuki, additional, Hayashi, Shintaro, additional, Masak, Katsuhisa, additional, Ogata, Hidenori, additional, Shinoda, Koji, additional, Uehara, Taira, additional, Watanabe, Mitsuru, additional, Yamaguchi, Hiroo, additional, Yamasaki, Ryo, additional, Yonekawa, Tomomi, additional, Jingu, Maki, additional, Nagano, Makiko, additional, Nakamura, Yumiko, additional, Sano, Yoshiko, additional, Araki, Manabu, additional, Lin, Youwei, additional, Mori, Madoka, additional, Mukai, Yohei, additional, Sano, Terunori, additional, Sato, Wakiro, additional, Gogun, Naoya, additional, Maeda, Yuriko, additional, Nishimoto, Asami, additional, Tsukamoto, Sachiko, additional, Yanagi, Ritsuko, additional, Saida, Takahiko, additional, Nakamura, Shinichi, additional, Nasu, Tetsuya, additional, Saida, Kyoko, additional, Shikata, Yuko, additional, Kodani, Yoshimi, additional, Saeki, Megumi, additional, Sawada, Yukako, additional, Yoshikawa, Hiroo, additional, Kimura, Takashi, additional, Nishi, Masamitsu, additional, Sakamoto, Shun, additional, Ukon, Shinichiro, additional, Watanabe, Shohei, additional, Ebisuya, Saori, additional, Kimura, Nami, additional, Matsuura, Manami, additional, Morisaki, Yukie, additional, Muroi, Yoshiko, additional, Onishi, Kuniko, additional, Oshima, Ikuko, additional, Washino, Yuki, additional, Yamashita, Tomomi, additional, Misu, Tatsuro, additional, Kaneko, Kimihiko, additional, Kato, Masaaki, additional, Kuroda, Hiroshi, additional, Kurosawa, Kazuhiro, additional, Nishiyama, Shuhei, additional, Ono, Hirohiko, additional, Takai, Yoshiki, additional, Abe, Keiko, additional, Hoshi, Hitomi, additional, Jinushi, Mari, additional, Oyama, Azusa, additional, Sakuma, Motonari, additional, Sawada, Yuko, additional, Ishibashi, Satoru, additional, Yokota, Takanori, additional, Nishida, Yoichiro, additional, Ozaki, Kokoro, additional, Sanjo, Nobuo, additional, Sato, Nozomu, additional, Denno, Fuki, additional, Hiraki, Haruko, additional, Matsubara, Yumi, additional, Kanda, Takashi, additional, Abe, Masaaki, additional, Honda, Masaya, additional, Kawai, Motoharu, additional, Koga, Michiaki, additional, Maeda, Toshihiko, additional, Ogasawara, Junichi, additional, Omoto, Masatoshi, additional, Sano, Yasuteru, additional, Sato, Ryota, additional, Shimizu, Fumitaka, additional, Arima, Hideki, additional, Fukui, Sachie, additional, Ishikawa, Yoshiko, additional, Koyama, Tomoko, additional, Shimose, Shigemi, additional, Shinozaki, Hirokazu, additional, Watanabe, Masanori, additional, Yasuda, Sachi, additional, Yoshiwaka, Chieko, additional, Adenan, Suffian, additional, Aris, Mohd Azman M, additional, Mawardi, Ahmad Shahir bin, additional, Adnan, Muhammad Al Hafiz, additional, Munusamy, Nanthini, additional, Razali, Siti Nur Omaira, additional, Somasundram, Punitha, additional, Hyun, Jae Won, additional, Jeong, In Hye, additional, Kim, Su-Hyun, additional, Shin, Hyun-June, additional, Yoo, Ji Sung, additional, Jang, HyunMin, additional, Joung, AeRan, additional, Kim, Byung-Jo, additional, Baek, Seol-Hee, additional, Kim, Jung Bin, additional, Kim, Yoo Hwan, additional, Koo, Yong Seo, additional, Lee, Chan Nyoung, additional, Seok, Hung Youl, additional, Hwang, Jinhee, additional, Kim, Sung Min, additional, Ahn, So Hyun, additional, Choi, Kyomin, additional, Choi, Seok-Jin, additional, Kim, Jun-Soon, additional, Kwon, Young Nam, additional, Shin, Je-Young, additional, Kwon, Hyeonju, additional, Kim, Byoung Joon, additional, Cho, Eun Bin, additional, Cho, Hye-Jin, additional, Choi, Misong, additional, Kim, DongSun, additional, Kim, Ju Hyeon, additional, Ki, SeungJu, additional, Lee, Hye Lim, additional, Lee, Kwang-Ho, additional, Min, Ju-Hong, additional, Park, Ji-Hyung, additional, Seok, Jinmyoung, additional, Choi, Eunhwa, additional, Park, Sang Ae, additional, Kim, Seung Min, additional, Jeong, Ha-Neul, additional, Jeongbin, Bong, additional, Jung, Jin Woo, additional, Kim, Seung Woo, additional, Kim, Yool-hee, additional, Lee, Hyung Seok, additional, Shin, Ha Young, additional, Jung, Yeon, additional, Kim, Min Jung, additional, Lee, Nou Ri, additional, Shin, MiJu, additional, Khabirov, Farit A, additional, Averyanova, Lyudmila, additional, Babicheva, Natalya, additional, Granatov, Eugenii, additional, Kazarov, Sergey, additional, Khaybullin, Timur, additional, Rogozhin, Alexander, additional, Pokhabov, Dmitry V, additional, Abramov, Vladislav, additional, Amelina, Anastasia, additional, Nesteroca, Yulia, additional, Bozhenkina, Tatyana, additional, Boyko, Aleksey N, additional, Demyan, Elena G, additional, Khoroshilova, Inessa, additional, Melnikov, Mikhail, additional, Popova, Ekaterina V, additional, Sharanova, Svetlana N, additional, Shchur, Sergey G, additional, Sazonov, Denis V, additional, Babenko, Larisa, additional, Bayandina, Elena, additional, Yarmoschuk, Asya, additional, Baliazin, Victor A, additional, Baliazina, Elena, additional, Budaeva, Elena, additional, Chernikova, Irina, additional, Goncharova, Zoya, additional, Krasnov, Vladimir, additional, Myatleva, Marina, additional, Rodionova, Olga V., additional, Samulyzhko, Iuliana, additional, Timofeeva, Alla A., additional, Duran, Sabas Boyero, additional, Bilbao, Maria Mar Mendibe, additional, Cuervo, Irene Diaz, additional, Domingo, Jose Maria Losada, additional, Eizaguirre, Amaia Gonzalez, additional, Llona, Jose Eulalio Barcena, additional, Moyano, Roberto Valverde, additional, Bahamonde, Carmen, additional, Lopez, Fernando Sanchez, additional, Morales, Raquel Pinar, additional, Morales, Eduardo Agüera, additional, Roman, Carmen Bahamonde, additional, Sepulveda, Juan Jose Ochoa, additional, Valero, Maria del Carmen Blanco, additional, Viña, Nazaret Pelaez, additional, Gavilan, Cristina Conde, additional, Sanchez, Ana Maria Jover, additional, Bedmar, Sara Vila, additional, Garcia, Nuria Gonzalez, additional, Garcia, Aida Orviz, additional, Gonzalez-Suarez, Ines, additional, Guillamon, Elena Miñano, additional, Kawiorski, Miguel, additional, Schulz, Elena Guerra, additional, Alonso, Alba Garcia, additional, Perez, Francisco Jesus Lopez, additional, Sarmiento, Marta Palacios, additional, Ayuso, Guillermo Izquierdo, additional, Mascarell, Guillermo Navarro, additional, Camino, Cristina Paramo, additional, Garcia, Asuncion Varas, additional, Mendoza, Yaiza Montserrat, additional, Muñoz, Veronica Ines Vargas, additional, Tonda, Patricia Torres, additional, Tsai, Ching-Piao, additional, Yin, Jiu-Haw, additional, Chen, Mei-Jung, additional, Li, Shan-Ni, additional, Wang, Fei-Ti, additional, Srisuwannanukorn, Suwat, additional, Boonmongkol, Thanatat, additional, Borisutbuathip, Duangporn, additional, Singwicha, Duangkamol, additional, Siritanan, Krittika, additional, Thearapati, Chidchanoke, additional, Sornda, Kwanmuang, additional, Apiwattanakul, Metha, additional, Aungsumart, Saharat, additional, Suanprasert, Narupat, additional, Suksuchano, Kaona, additional, Parkinsee, Nittaya, additional, Kulkantrakorn, Kongkiat, additional, Lolekha, Praween, additional, Potigumjon, Artit, additional, Sukphulloprat, Puchit, additional, Suksasunee, Dararat, additional, Komaratat, Chankawee, additional, Luangtong, Sunattana, additional, Arayawichanont, Arkhom, additional, Konpan, Phanpaphon, additional, Riablershirun, Nathapol, additional, Wiroteurairuang, Thaddao, additional, Jantaweesirirat, Panadda, additional, Kurne, Aslı, additional, Erkent, Irem, additional, Kurt, Ebru Bekircan, additional, Saylam, Ezgi, additional, Caliskan, Yagmur, additional, Orsel, Gulsah, additional, Celik, Yahya, additional, Celebi, Canan, additional, Tekatas, Aslan, additional, Banbal, Tugce, additional, Demir, Gulsen Akman, additional, Altunrende, Burcu, additional, Matur, Zeliha, additional, Topcular, Baris, additional, Elmas, Tules, additional, Gulo, Aysenur, additional, Ozdemir, Selin, additional, Ozkoklesen, Cansu, additional, Ozturk, Mahinur, additional, Yanik, Mertkan, additional, Yildirim, Elif, additional, Tutuncu, Melih, additional, Altintas, Ayse, additional, Cam, Abdulsamet, additional, Elmali, Ayse Deniz, additional, Saip, Sabahattin, additional, Siva, Aksel, additional, Tanrıverdi, Uygur, additional, Uygunoglu, Ugur, additional, Caliskan, Sinem, additional, Gulo, Pinar, additional, Kozig, Esra, additional, Sakiz, Sakine, additional, Sengun, Ihsan Sukru, additional, Idiman, Egemen, additional, Ala, Rahmi Tumay, additional, Arslan, Duygu, additional, Bulut, Utku, additional, Karakaptan, Yasemin, additional, Kaya, Derya, additional, Mehdiyev, Zaur, additional, Balkan, Bengu, additional, Kuku, Berfu, additional, Ozhun, Mujgan, additional, Tuga, Celal, additional, Ugur, Muzeyyen, additional, Efendi, Husnu, additional, Bunul, Sena Destan, additional, Cavus, Hakan, additional, Gorke, Yunus Emre, additional, Kutlu, Ayse, additional, Ozturk, Seda, additional, Sarikaya, Cansu Egilmez, additional, Becerikli, Gulsah, additional, Semiz, Cansu, additional, Tun, Ozlem, additional, Ayer, Sehriban, additional, Onar, Musa Kazim, additional, Ozberk, Mehlika Berra, additional, Sen, Sedat, additional, Cavdar, Tugce Kirbas, additional, Veske, Adife, additional, Boz, Cavit, additional, Altiparmak, Didem, additional, Aydin, Cigdem Ozen, additional, Gazioglu, Sibel, additional, Bekircan, Duygu, additional, Jacob, Anu, additional, Arndt, Heike, additional, Elsone, Liene, additional, Hamid, Shahd Hassan Mahmoud, additional, Whittam, Daniel Hugh, additional, Wilson, Martin, additional, O'Brien, Imelda, additional, Leite, Maria Isabel da Silva, additional, Cruz, Pedro Maria Rodriguez, additional, Jenkins, Damian Robert, additional, Tackley, George, additional, Cavey, Ana, additional, Everett, Rosie, additional, Hodder, Joy, additional, Koelewyn, Abigail, additional, Mowry, Ellen, additional, Royal, Walter, additional, Shin, Robert, additional, Bever, Christopher, additional, Harrison, Daniel, additional, Rus, Horea, additional, Zheng, Wei, additional, Callison, Karen, additional, Naunton, Kerry, additional, Frishberg, Benjamin M, additional, Blumenfeld, Andrew M, additional, Inocelda, Andrew, additional, Korabathina, Kalyani, additional, Lobatz, Michael, additional, Mortin, Melissa M, additional, Oh, Irene J, additional, Rosenberg, Jay H, additional, Sadoff, Mark, additional, Sahagian, Gregory A, additional, Wang, Anchi, additional, Camberos, Yasmin, additional, Sanchez, Guadalupe, additional, Soto, Estela, additional, Nicholas, Jacqueline A, additional, Boster, Aaron, additional, Eubank, Geoffrey, additional, Groezinger, Katy, additional, Lauf, Meghan, additional, Okai, Annette F, additional, Hasan, Rashedul, additional, Khoury, Chaouki, additional, Stokes, Victoria, additional, Clardy, Stacey, additional, Cortez, Melissa, additional, Greenlee, John, additional, Rose, John, additional, Soldan, Mateo Paz, additional, Emett, Amanda, additional, Esquibel, Lawanda, additional, Fagatele, Lilly, additional, Wong, Ka-Ho, additional, Stevens, James C, additional, Banas, Thomas M, additional, Bultemeyer, Marlene C, additional, Haller, Andrea, additional, Manalo, Natalie, additional, Aeschliman, Keri, additional, Kocks, Debi, additional, Racke, Michael, additional, Boster, Aaron Lee, additional, Bowman, Michelle, additional, Imitola, Jaime, additional, Kisanuki, Yasushi, additional, Green, Misty, additional, Scarberry, Stephanie, additional, Lynch, Sharon G, additional, Anderson, Heather S, additional, Gronseth, Gary S, additional, Hammond, Nancy E, additional, Jassam, Yasir N, additional, Mittal, Manoj K, additional, Nashatizadeh, Muhammed M, additional, Levine, Nicholas, additional, Schmidt, Lisa, additional, Sibley, Jill, additional, Whitley, Vonda, additional, Winkley, James, additional, Coleman, Timothy, additional, Cooper, Gregory, additional, Sheffield, Stephanie, additional, Turner, Keri, additional, Galloway, Dana, additional, Tillett, Robert S, additional, Ganesh, Geeta A, additional, Plato, Brian M, additional, Seifert, Tad D, additional, Godwin, Diana, additional, Lockridge, Deborah, additional, Rammohan, Kottil W, additional, Sheremata, William A, additional, Delgado, Silvia, additional, Gonzalez, Jose, additional, Lizarraga, Alexis, additional, Maldonado, Janice, additional, Ortega, Melissa, additional, Tornes, Leticia, additional, Babcock, Yanet, additional, Cailam, Osmara, additional, Campos, Yesica, additional, Couvertier, Irlisse, additional, Daneri, Bettina, additional, Deni, Jeremy, additional, Hernandez, Jeffrey, additional, Jaramillo, Tatiana, additional, Morris, Tenita, additional, Nobel, Daniel, additional, Oliveira, Anjelis, additional, Richardson, Reshma, additional, Rodriguez, Gloria, additional, Romero, Ana, additional, Sandova, Carlos, additional, Sawant, Ruta, additional, Tueros, Lissett, additional, Zetka, Eric S, additional, Zheng, Chao, additional, Jacobs, Daniel H, additional, Easterling, Constance, additional, Fairbank, Jennifer, additional, Iyengar, Revathi, additional, Klafter, Mark, additional, Lindquist, Justin, additional, Sadek, Ahmed H, additional, Toro, Elizabeth Carmona, additional, Verma, Navin, additional, Castro, Brigith Patino, additional, Sukhraj-Singh, Nadia, additional, Berger, Joseph, additional, Williamson, Eric, additional, Chahin, Salim, additional, Jacobs, Dina, additional, Markowitz, Clyde, additional, Dobbins, Jessica, additional, Mace, Lauren, additional, Martin, Maria, additional, Pinckney, Ashley, additional, Roberts, Amber, additional, Zaydan, Islam, additional, Mitchell, Galen W, additional, Heyman, Rock A, additional, Orie, Ryan L, additional, Suski, Valerie R, additional, Oddis, Kerry, additional, Punjack, Darlene, additional, Flanagan, Eoin, additional, Gadoth, Avi, additional, McKeon, Andrew, additional, Tobin, W Oliver, additional, Zekeridou, Anastasia, additional, Dunlay, Katie, additional, Sagen, Jessica, additional, Carter, Jonathan L, additional, Estephan, Bachir, additional, Goodman, Brent P, additional, Snyder, Charlene R Hoffman, additional, Francone, Andrea, additional, Galasky, Irene, additional, Thomas, Martha, additional, Repovic, Pavle, additional, Bowen, James, additional, Mayadev, Angeli, additional, Qian, Peiqing, additional, Courtney, Yuriko, additional, Lennox, Lauren, additional, Naismith, Robert Thomas, additional, Cross, Anne Haney, additional, Evans, Emily, additional, Longbrake, Erin E, additional, Orchard, Megan E, additional, Wu, Gregory F, additional, Heinrich, Linda, additional, Sommers, Susan, additional, Amjad, Faria, additional, Mitchell, Erika, additional, Mora, Carlos, additional, Schreiber, Bethany, additional, Tornatore, Carlo, additional, Carlson, Alexis, additional, McCarthy, Sacha, additional, and Oliver, Alexandria, additional

Published
2021
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22. Gray matter atrophy in relapsing-remitting multiple sclerosis is associated with white matter lesions in connecting fibers.

Author

Bussas, Matthias, Grahl, Sophia, Pongratz, Viola, Berthele, Achim, Gasperi, Christiane, Andlauer, Till, Gaser, Christian, Kirschke, Jan S, Wiestler, Benedikt, Zimmer, Claus, Hemmer, Bernhard, and Mühlau, Mark

Subjects
GRAY matter (Nerve tissue), WHITE matter (Nerve tissue), CEREBRAL atrophy, ATROPHY, MULTIPLE sclerosis
Abstract

Background: Lesions of brain white matter (WM) and atrophy of brain gray matter (GM) are well-established surrogate parameters in multiple sclerosis (MS), but it is unclear how closely these parameters relate to each other. Objective: To assess across the whole cerebrum whether GM atrophy can be explained by lesions in connecting WM tracts. Methods: GM images of 600 patients with relapsing-remitting MS (women = 68%; median age = 33.0 years, median expanded disability status scale score = 1.5) were converted to atrophy maps by data from a healthy control cohort. An atlas of WM tracts from the Human Connectome Project and individual lesion maps were merged to identify potentially disconnected GM regions, leading to individual disconnectome maps. Across the whole cerebrum, GM atrophy and potentially disconnected GM were tested for association both cross-sectionally and longitudinally. Results: We found highly significant correlations between disconnection and atrophy across most of the cerebrum. Longitudinal analysis demonstrated a close temporal relation of WM lesion formation and GM atrophy in connecting fibers. Conclusion: GM atrophy is associated with WM lesions in connecting fibers. Caution is warranted when interpreting group differences in GM atrophy exclusively as differences in early neurodegeneration independent of WM lesion formation. [ABSTRACT FROM AUTHOR]

Published
2022
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23. CSF Protein Concentration Shows No Correlation With Brain Volume Measures

Author

Wuschek, Alexander, Grahl, Sophia, Pongratz, Viola, Korn, Thomas, Kirschke, Jan, Zimmer, Claus, Hemmer, Bernhard, and Mühlau, Mark

Subjects
Neurology, brain volume, CSF, Neurology (clinical), Brief Research Report, protein, albumin, MRI
Abstract

Background: CSF protein concentrations vary greatly among individuals. Accounting for brain volume may lower the variance and increase the diagnostic value of CSF protein concentrations. Objective: To determine the relation between CSF protein concentrations and brain volume. Methods: Brain volumes (total intracranial, gray matter, white matter volumes) derived from brain MRI and CSF protein concentrations (total protein, albumin, albumin CSF/serum ratio) of 29 control patients and 497 patients with clinically isolated syndrome or multiple sclerosis were studied. Finding: We found significant positive correlations of CSF protein concentrations with intracranial, gray matter, and white matter volumes. None of the correlations remained significant after correction for age and sex. Conclusion: Accounting for brain volume derived from brain MRI is unlikely to improve the diagnostic value of protein concentrations in CSF.

Published
2019

24. Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Author

Mitrovič, Mitja, primary, Patsopoulos, Nikolaos A., additional, Beecham, Ashley H., additional, Dankowski, Theresa, additional, Goris, An, additional, Dubois, Bénédicte, additional, D’hooghe, Marie B., additional, Lemmens, Robin, additional, Van Damme, Philip, additional, Søndergaard, Helle Bach, additional, Sellebjerg, Finn, additional, Sorensen, Per Soelberg, additional, Ullum, Henrik, additional, Thørner, Lise W., additional, Werge, Thomas, additional, Saarela, Janna, additional, Cournu-Rebeix, Isabelle, additional, Damotte, Vincent, additional, Fontaine, Bertrand, additional, Guillot-Noel, Lena, additional, Lathrop, Mark, additional, Vukusik, Sandra, additional, Gourraud, Pierre-Antoine, additional, Andlauer, Till F.M., additional, Pongratz, Viola, additional, Buck, Dorothea, additional, Gasperi, Christiane, additional, Bayas, Antonios, additional, Heesen, Christoph, additional, Kümpfel, Tania, additional, Linker, Ralf, additional, Paul, Friedemann, additional, Stangel, Martin, additional, Tackenberg, Björn, additional, Bergh, Florian Then, additional, Warnke, Clemens, additional, Wiendl, Heinz, additional, Wildemann, Brigitte, additional, Zettl, Uwe, additional, Ziemann, Ulf, additional, Tumani, Hayrettin, additional, Gold, Ralf, additional, Grummel, Verena, additional, Hemmer, Bernhard, additional, Knier, Benjamin, additional, Lill, Christina M., additional, Luessi, Felix, additional, Dardiotis, Efthimios, additional, Agliardi, Cristina, additional, Barizzone, Nadia, additional, Mascia, Elisabetta, additional, Bernardinelli, Luisa, additional, Comi, Giancarlo, additional, Cusi, Daniele, additional, Esposito, Federica, additional, Ferrè, Laura, additional, Comi, Cristoforo, additional, Galimberti, Daniela, additional, Leone, Maurizio A., additional, Sorosina, Melissa, additional, Mescheriakova, Julia, additional, Hintzen, Rogier, additional, van Duijn, Cornelia, additional, Teunissen, Charlotte E., additional, Bos, Steffan D., additional, Myhr, Kjell-Morten, additional, Celius, Elisabeth G., additional, Lie, Benedicte A., additional, Spurkland, Anne, additional, Comabella, Manuel, additional, Montalban, Xavier, additional, Alfredsson, Lars, additional, Stridh, Pernilla, additional, Hillert, Jan, additional, Jagodic, Maja, additional, Piehl, Fredrik, additional, Jelčić, Ilijas, additional, Martin, Roland, additional, Sospedra, Mireia, additional, Ban, Maria, additional, Hawkins, Clive, additional, Hysi, Pirro, additional, Kalra, Seema, additional, Karpe, Fredrik, additional, Khadake, Jyoti, additional, Lachance, Genevieve, additional, Neville, Matthew, additional, Santaniello, Adam, additional, Caillier, Stacy J., additional, Calabresi, Peter A., additional, Cree, Bruce A.C., additional, Cross, Anne, additional, Davis, Mary F., additional, Haines, Jonathan L., additional, de Bakker, Paul I.W., additional, Delgado, Silvia, additional, Dembele, Marieme, additional, Edwards, Keith, additional, Fitzgerald, Kathryn C., additional, Hakonarson, Hakon, additional, Konidari, Ioanna, additional, Lathi, Ellen, additional, Manrique, Clara P., additional, Pericak-Vance, Margaret A., additional, Piccio, Laura, additional, Schaefer, Cathy, additional, McCabe, Cristin, additional, Weiner, Howard, additional, Goldstein, Jacqueline, additional, Olsson, Tomas, additional, Hadjigeorgiou, Georgios, additional, Taylor, Bruce, additional, Tajouri, Lotti, additional, Charlesworth, Jac, additional, Booth, David R., additional, Harbo, Hanne F., additional, Ivinson, Adrian J., additional, Hauser, Stephen L., additional, Compston, Alastair, additional, Stewart, Graeme, additional, Zipp, Frauke, additional, Barcellos, Lisa F., additional, Baranzini, Sergio E., additional, Martinelli-Boneschi, Filippo, additional, D’Alfonso, Sandra, additional, Ziegler, Andreas, additional, Oturai, Annette, additional, McCauley, Jacob L., additional, Sawcer, Stephen J., additional, Oksenberg, Jorge R., additional, De Jager, Philip L., additional, Kockum, Ingrid, additional, Hafler, David A., additional, and Cotsapas, Chris, additional

Published
2020
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27. Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Author

Int Multiple Sclerosis Genetics, Mitrovic, Mitja, Patsopoulos, Nikoloas, Beecham, Ashley, Dankowski, Theresa, Goris, An, Dubois, Bénédicte, D'hooghe, Marie B, Lemmens, Robin, Van Damme, Philip, Bach Sondergaard, Helle, Sellebjerg, Finn, Soelberg Sorensen, Per, Ullum, Henrik, Thorner, Lise W, Werge, Thomas, Saarela, Janna, Cournu-Rebeix, Isabelle, Damotte, Vincent, Fontaine, Bertrand, Guillot-Noel, Lena, Lathrop, Mark, Vukusik, Sandra, Gourraud, Pierre-Antoine, Andlauer, Till FM, Pongratz, Viola, Buck, Dorothea, Gasperi, Christiane, Bayas, Antonios, Heesen, Christoph, Kümpfel, Tania, Linker, Ralf, Friedemann, Paul, Stangel, Martin, Tackenberg, Björn, Then Bergh, Florian, Warnke, Clemens, Wiendl, Heinz, Wildemann, Brigitte, Zettl, Uwe, Ziemann, Ulf, Tumani, Hayrettin, Gold, Ralf, Grummel, Verena, Hemmer, Bernhard, Knier, Benjamin, Lill, Christina, Luessi, Felix, Dardiotis, Efthimios, Agliardi, Cristina, Barizzone, Nadia, Mascia, Elisabetta, Bernardinelli, Luisa, Comi, Giancarlo, Cusi, Daniele, Esposito, Federica, Ferrè, Laura, Comi, Cristoforo, Galimberti, Daniela, Leone, Maurizio A, Sorosina, Melissa, Mescheriakova, Julia, Hintzen, Rogier, van Duijn, Cornelia, Theunissen, Charlotte E, Bos, Steffan D, Myhr, Kjell-Morten, Celius, Elisabeth G, Lie, Benedicte A, Spurkland, Anne, Comabella, Manuel, Montalban, Xavier, Alfredsson, Lars, Stridh, Pernilla, Hillert, Jan, Jagodic, Maja, Piehl, Fredrik, Jelcic, Ilijas, Martin, Roland, Sospedra, Mireia, Ban, Maria, Hawkins, Clive, Hysi, Pirro, Kalra, Seema, Karpe, Fredrik, Khadake, Jyoti, Lachance, Genevieve, Neville, Matthew, Santaniello, Adam, Caillier, Stacy J, Calavresi, Peter A, Cree, Bruce AC, Cross, Anne, Davis, Mary F, Haines, Jonathan L, de Bakker, Paul IW, Delgado, Silvia, Dembele, Marieme, Edwards, Keith, Fitzgerald, Kathryn C, Hakonarson, Hakon, Konidari, Ioanna, Lathi, Ellen, Manrique, Clara P, Pericak-Vance, Margaret A, Piccio, Laura, Schaefer, Cathy, McCabe, Cristin, Weiner, Howard, Goldstein, Jacqueline, Olsson, Tomas, Hadjigeorgiou, Georgios, Taylor, Bruce, Tajouri, Lotti, Charlesworth, Jac, Booth, David R, HArbo, Hanne F, Ivinson, Adrian J, Hauser, Stephen L, Compston, Alistair, Stewart, Graeme, Zipp, Frauke, Barcellos, Lisa F, Baranzini, Sergio E, Martinelli-Boneschi, Filippo, D'Alfonso, Sandra, Ziegler, Andreas, Oturai, Annette, McCauley, Jacob L, Sawcer, Stephen J, Oksenberg, Jorge R, De Jager, Philip L, Kockum, Ingrid, Hafler, David A, and Cotsapas, Chris

Subjects
Biochemistry & Molecular Biology, Science & Technology, REPLICATION, LINKAGE, Cell Biology, GENETIC RISK, GENOME-WIDE ASSOCIATION, VARIANTS, Life Sciences & Biomedicine, METAANALYSIS, POPULATION
Abstract

Multiple sclerosis is a complex neurological disease, with ∼20% of risk heritability attributable to common genetic variants, including >230 identified by genome-wide association studies. Multiple strands of evidence suggest that much of the remaining heritability is also due to additive effects of common variants rather than epistasis between these variants or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that up to 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common-variant signals, highlighting key pathogenic roles for regulatory T cell homeostasis and regulation, IFNγ biology, and NFκB signaling. As low-frequency variants do not show substantial linkage disequilibrium with other variants, and as coding variants are more interpretable and experimentally tractable than non-coding variation, our discoveries constitute a rich resource for dissecting the pathobiology of MS. ispartof: CELL vol:175 issue:6 pages:1679-1695 ispartof: location:United States status: published

Published
2018

29. Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Author

Mitrovič, Mitja, primary, Patsopoulos, Nikolaos A., additional, Beecham, Ashley H., additional, Dankowski, Theresa, additional, Goris, An, additional, Dubois, Bénédicte, additional, D’hooghe, Marie B., additional, Lemmens, Robin, additional, Van Damme, Philip, additional, Søndergaard, Helle Bach, additional, Sellebjerg, Finn, additional, Sorensen, Per Soelberg, additional, Ullum, Henrik, additional, Thørner, Lise W., additional, Werge, Thomas, additional, Saarela, Janna, additional, Cournu-Rebeix, Isabelle, additional, Damotte, Vincent, additional, Fontaine, Bertrand, additional, Guillot-Noel, Lena, additional, Lathrop, Mark, additional, Vukusik, Sandra, additional, Gourraud, Pierre-Antoine, additional, Andlauer, Till F.M., additional, Pongratz, Viola, additional, Buck, Dorothea, additional, Gasperi, Christiane, additional, Bayas, Antonios, additional, Heesen, Christoph, additional, Kümpfel, Tania, additional, Linker, Ralf, additional, Paul, Friedemann, additional, Stangel, Martin, additional, Tackenberg, Björn, additional, Bergh, Florian Then, additional, Warnke, Clemens, additional, Wiendl, Heinz, additional, Wildemann, Brigitte, additional, Zettl, Uwe, additional, Ziemann, Ulf, additional, Tumani, Hayrettin, additional, Gold, Ralf, additional, Grummel, Verena, additional, Hemmer, Bernhard, additional, Knier, Benjamin, additional, Lill, Christina M., additional, Luessi, Felix, additional, Dardiotis, Efthimios, additional, Agliardi, Cristina, additional, Barizzone, Nadia, additional, Mascia, Elisabetta, additional, Bernardinelli, Luisa, additional, Comi, Giancarlo, additional, Cusi, Daniele, additional, Esposito, Federica, additional, Ferrè, Laura, additional, Comi, Cristoforo, additional, Galimberti, Daniela, additional, Leone, Maurizio A., additional, Sorosina, Melissa, additional, Mescheriakova, Julia, additional, Hintzen, Rogier, additional, van Duijn, Cornelia, additional, Teunissen, Charlotte E., additional, Bos, Steffan D., additional, Myhr, Kjell-Morten, additional, Celius, Elisabeth G., additional, Lie, Benedicte A., additional, Spurkland, Anne, additional, Comabella, Manuel, additional, Montalban, Xavier, additional, Alfredsson, Lars, additional, Stridh, Pernilla, additional, Hillert, Jan, additional, Jagodic, Maja, additional, Piehl, Fredrik, additional, Jelčić, Ilijas, additional, Martin, Roland, additional, Sospedra, Mireia, additional, Ban, Maria, additional, Hawkins, Clive, additional, Hysi, Pirro, additional, Kalra, Seema, additional, Karpe, Fredrik, additional, Khadake, Jyoti, additional, Lachance, Genevieve, additional, Neville, Matthew, additional, Santaniello, Adam, additional, Caillier, Stacy J., additional, Calabresi, Peter A., additional, Cree, Bruce A.C., additional, Cross, Anne, additional, Davis, Mary F., additional, Haines, Jonathan L., additional, de Bakker, Paul I.W., additional, Delgado, Silvia, additional, Dembele, Marieme, additional, Edwards, Keith, additional, Fitzgerald, Kathryn C., additional, Hakonarson, Hakon, additional, Konidari, Ioanna, additional, Lathi, Ellen, additional, Manrique, Clara P., additional, Pericak-Vance, Margaret A., additional, Piccio, Laura, additional, Schaefer, Cathy, additional, McCabe, Cristin, additional, Weiner, Howard, additional, Goldstein, Jacqueline, additional, Olsson, Tomas, additional, Hadjigeorgiou, Georgios, additional, Taylor, Bruce, additional, Tajouri, Lotti, additional, Charlesworth, Jac, additional, Booth, David R., additional, Harbo, Hanne F., additional, Ivinson, Adrian J., additional, Hauser, Stephen L., additional, Compston, Alastair, additional, Stewart, Graeme, additional, Zipp, Frauke, additional, Barcellos, Lisa F., additional, Baranzini, Sergio E., additional, Martinelli-Boneschi, Filippo, additional, D’Alfonso, Sandra, additional, Ziegler, Andreas, additional, Oturai, Annette, additional, McCauley, Jacob L., additional, Sawcer, Stephen J., additional, Oksenberg, Jorge R., additional, De Jager, Philip L., additional, Kockum, Ingrid, additional, Hafler, David A., additional, and Cotsapas, Chris, additional

Published
2019
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30. Accuracy of Unenhanced MRI in the Detection of New Brain Lesions in Multiple Sclerosis

Author

Eichinger, Paul, primary, Schön, Simon, additional, Pongratz, Viola, additional, Wiestler, Hanni, additional, Zhang, Haike, additional, Bussas, Matthias, additional, Hoshi, Muna-Miriam, additional, Kirschke, Jan, additional, Berthele, Achim, additional, Zimmer, Claus, additional, Hemmer, Bernhard, additional, Mühlau, Mark, additional, and Wiestler, Benedikt, additional

Published
2019
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31. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

Author

Patsopoulos, Nikolaos A., Baranzini, Sergio E., Santaniello, Adam, Shoostari, Parisa, Cotsapas, Chris, Wong, Garrett, Beecham, Ashley H., James, Tojo, Replogle, Joseph, Vlachos, Ioannis S., McCabe, Cristin, Pers, Tune H., Brandes, Aaron, White, Charles, Keenan, Brendan, Cimpean, Maria, Winn, Phoebe, Panteliadis, Ioannis Pavlos, Robbins, Allison, Andlauer, Till F.M., Zarzycki, Onigiusz, Dubois, Bénédicte, Goris, An, Søndergaard, Helle Bach, Sellebjerg, Finn, Sorensen, Per Soelberg, Ullum, Henrik, Thørner, Lise Wegner, Saarela, Janna, Cournu-Rebeix, Isabelle, Damotte, Vincent, Fontaine, Bertrand, Guillot-Noel, Lena, Lathrop, Mark, Vukusic, Sandra, Berthele, Achim, Pongratz, Viola, Buck, Dorothea, Gasperi, Christiane, Graetz, Christiane, Grummel, Verena, Hemmer, Bernhard, Hoshi, Muni, Knier, Benjamin, Korn, Thomas, Lill, Christina M., Luessi, Felix, Karpe, Fredrik, Lage, Kasper, Oturai, Annette, Patsopoulos, Nikolaos A., Baranzini, Sergio E., Santaniello, Adam, Shoostari, Parisa, Cotsapas, Chris, Wong, Garrett, Beecham, Ashley H., James, Tojo, Replogle, Joseph, Vlachos, Ioannis S., McCabe, Cristin, Pers, Tune H., Brandes, Aaron, White, Charles, Keenan, Brendan, Cimpean, Maria, Winn, Phoebe, Panteliadis, Ioannis Pavlos, Robbins, Allison, Andlauer, Till F.M., Zarzycki, Onigiusz, Dubois, Bénédicte, Goris, An, Søndergaard, Helle Bach, Sellebjerg, Finn, Sorensen, Per Soelberg, Ullum, Henrik, Thørner, Lise Wegner, Saarela, Janna, Cournu-Rebeix, Isabelle, Damotte, Vincent, Fontaine, Bertrand, Guillot-Noel, Lena, Lathrop, Mark, Vukusic, Sandra, Berthele, Achim, Pongratz, Viola, Buck, Dorothea, Gasperi, Christiane, Graetz, Christiane, Grummel, Verena, Hemmer, Bernhard, Hoshi, Muni, Knier, Benjamin, Korn, Thomas, Lill, Christina M., Luessi, Felix, Karpe, Fredrik, Lage, Kasper, and Oturai, Annette

Abstract

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.

Published
2019

32. Frontiers in Molecular Neuroscience / Geostatistical Analysis of White Matter Lesions in Multiple Sclerosis Identifies Gender Differences in Lesion Evolution

Author

Marschallinger, Robert, Mühlau, Mark, Pongratz, Viola, Kirschke, Jan S., Marschallinger, Simon, Schmidt, Paul, and Sellner, Johann

Subjects
white matter lesion evolution, gender differences, time series analysis, lesion segmentation, geostatistics, 4D analysis, multiple Sclerosis
Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with presumed autoimmune origin. The development of lesions within the gray matter and white matter, which are highly variable with respect to number, total volume, morphology and spatial evolution and which only show a limited correlation with clinical disability, is a hallmark of the disease. Population-based studies indicate a distinct outcome depending on gender. Here, we studied gender-related differences in the evolution of white matter MS-lesions (MS-WML) in early MS by using geostatistical methods. Within a 3 years observation period, a female and a male MS patient group received disease modifying drugs and underwent standardized annual brain magnetic resonance imaging, accompanied by neurological examination. MS-WML were automatically extracted and the derived binary lesion masks were subject to geostatistical analysis, yielding quantitative spatial-statistics metrics on MS-WML pattern morphology and total lesion volume (TLV). Through the MS-lesion pattern discrimination plot, the following differences were disclosed: corresponding to gender and MS-WML pattern morphology at baseline, two female subgroups (F1, F2) and two male subgroups (M1, M2) are discerned that follow a distinct MS-WML pattern evolution in space and time. F1 and M1 start with medium-level MS-WML pattern smoothness and TLV, both behave longitudinally quasi-static. By contrast, F2 and M2 start with high-level MS-WML pattern smoothness and medium-level TLV. F2 and M2 longitudinal development is characterized by strongly diminishing MS-WML pattern smoothness and TLV, i.e., continued shrinking and break-up of MS-WML. As compared to the male subgroup M2, the female subgroup F2 shows continued, increased MS-WML pattern smoothness and TLV. Data from neurological examination suggest a correlation of MS-WML pattern morphology metrics and EDSS. Our results justify detailed studies on gender-related differences. (VLID)3387368

Published
2018
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34. Comparing myelin-sensitive markers MWF, ihMTR, and MTsat in healthy and normal-appearing brain tissue and multiple sclerosis lesions

Author

Berg, Ronja, primary, Pongratz, Viola, additional, Lauerer, Markus, additional, Amthor, Thomas, additional, Gilbert, Guillaume, additional, Menegaux, Aurore, additional, Zimmer, Claus, additional, Sorg, Christian, additional, Doneva, Mariya, additional, Vavasour, Irene, additional, Mühlau, Mark, additional, and Preibisch, Christine, additional

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