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1. Sequence variants influencing the regulation of serum IgG subclass levels

Author

Olafsdottir, Thorunn A., Thorleifsson, Gudmar, Lopez de Lapuente Portilla, Aitzkoa, Jonsson, Stefan, Stefansdottir, Lilja, Niroula, Abhishek, Jonasdottir, Aslaug, Eggertsson, Hannes P., Halldorsson, Gisli H., Thorlacius, Gudny E., Arnthorsson, Asgeir O., Bjornsdottir, Unnur S., Asselbergs, Folkert W., Bentlage, Arthur E. H., Eyjolfsson, Gudmundur I., Gudmundsdottir, Steinunn, Gunnarsdottir, Kristbjorg, Halldorsson, Bjarni V., Holm, Hilma, Ludviksson, Bjorn R., Melsted, Pall, Norddahl, Gudmundur L., Olafsson, Isleifur, Saevarsdottir, Saedis, Sigurdardottir, Olof, Sigurdsson, Asgeir, Temming, Robin, Önundarson, Pall T., Thorsteinsdottir, Unnur, Vidarsson, Gestur, Sulem, Patrick, Gudbjartsson, Daniel F., Jonsdottir, Ingileif, Nilsson, Björn, and Stefansson, Kari

Published
2024
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2. Sequence variant affects GCSAML splicing, mast cell specific proteins, and risk of urticaria

Author

Kristjansson, Ragnar P., Oskarsson, Gudjon R., Skuladottir, Astros, Oddsson, Asmundur, Rognvaldsson, Solvi, Sveinbjornsson, Gardar, Lund, Sigrun H., Jensson, Brynjar O., Styrmisdottir, Edda L., Halldorsson, Gisli H., Ferkingstad, Egil, Eldjarn, Grimur Hjorleifsson, Beyter, Doruk, Kristmundsdottir, Snædis, Juliusson, Kristinn, Fridriksdottir, Run, Arnadottir, Gudny A., Katrinardottir, Hildigunnur, Snorradottir, Margret H., Tragante, Vinicius, Stefansdottir, Lilja, Ivarsdottir, Erna V., Bjornsdottir, Gyda, Halldorsson, Bjarni V., Thorleifsson, Gudmar, Ludviksson, Bjorn R., Onundarson, Pall T., Saevarsdottir, Saedis, Melsted, Pall, Norddahl, Gudmundur L., Bjornsdottir, Unnur S., Olafsdottir, Thorunn, Gudbjartsson, Daniel F., Thorsteinsdottir, Unnur, Jonsdottir, Ingileif, Sulem, Patrick, and Stefansson, Kari

Published
2023
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3. FLT3 stop mutation increases FLT3 ligand level and risk of autoimmune thyroid disease

Author

Saevarsdottir, Saedis, Olafsdottir, Thorunn A., Ivarsdottir, Erna V., Halldorsson, Gisli H., Gunnarsdottir, Kristbjorg, Sigurdsson, Asgeir, Johannesson, Ari, Sigurdsson, Jon K., Juliusdottir, Thorhildur, Lund, Sigrun H., Arnthorsson, Asgeir O., Styrmisdottir, Edda L., Gudmundsson, Julius, Grondal, Gerdur M., Steinsson, Kristjan, Alfredsson, Lars, Askling, Johan, Benediktsson, Rafn, Bjarnason, Ragnar, Geirsson, Arni J., Gudbjornsson, Bjorn, Gudjonsson, Hallgrimur, Hjaltason, Haukur, Hreidarsson, Astradur B., Klareskog, Lars, Kockum, Ingrid, Kristjansdottir, Helga, Love, Thorvardur J., Ludviksson, Bjorn R., Olsson, Tomas, Onundarson, Pall T., Orvar, Kjartan B., Padyukov, Leonid, Sigurgeirsson, Bardur, Tragante, Vinicius, Bjarnadottir, Kristbjorg, Rafnar, Thorunn, Masson, Gisli, Sulem, Patrick, Gudbjartsson, Daniel F., Melsted, Pall, Thorleifsson, Gudmar, Norddahl, Gudmundur L., Thorsteinsdottir, Unnur, Jonsdottir, Ingileif, and Stefansson, Kari

Published
2020
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4. A loss-of-function variant in ALOX15 protects against nasal polyps and chronic rhinosinusitis

Author

Kristjansson, Ragnar P., Benonisdottir, Stefania, Davidsson, Olafur B., Oddsson, Asmundur, Tragante, Vinicius, Sigurdsson, Jon K., Stefansdottir, Lilja, Jonsson, Stefan, Jensson, Brynjar O., Arthur, Joseph G., Arnadottir, Gudny A., Sulem, Gerald, Halldorsson, Bjarni V., Gunnarsson, Bjarni, Halldorsson, Gisli H., Stefansson, Olafur A., Oskarsson, Gudjon R., Deaton, Aimee M., Olafsson, Isleifur, Eyjolfsson, Gudmundur I., Sigurdardottir, Olof, Onundarson, Pall T., Gislason, David, Gislason, Thorarinn, Ludviksson, Bjorn R., Ludviksdottir, Dora, Olafsdottir, Thorunn A., Rafnar, Thorunn, Masson, Gisli, Zink, Florian, Bjornsdottir, Gyda, Magnusson, Olafur Th., Bjornsdottir, Unnur S., Thorleifsson, Gudmar, Norddahl, Gudmundur L., Gudbjartsson, Daniel F., Thorsteinsdottir, Unnur, Jonsdottir, Ingileif, Sulem, Patrick, and Stefansson, Kari

Published
2019
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5. Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis

Author

Olafsdottir, Thorunn A., Theodors, Fannar, Bjarnadottir, Kristbjorg, Bjornsdottir, Unnur Steina, Agustsdottir, Arna B., Stefansson, Olafur A., Ivarsdottir, Erna V., Sigurdsson, Jon K., Benonisdottir, Stefania, Eyjolfsson, Gudmundur I., Gislason, David, Gislason, Thorarinn, Guðmundsdóttir, Steinunn, Gylfason, Arnaldur, Halldorsson, Bjarni V., Halldorsson, Gisli H., Juliusdottir, Thorhildur, Kristinsdottir, Anna M., Ludviksdottir, Dora, Ludviksson, Bjorn R., Masson, Gisli, Norland, Kristjan, Onundarson, Pall T., Olafsson, Isleifur, Sigurdardottir, Olof, Stefansdottir, Lilja, Sveinbjornsson, Gardar, Tragante, Vinicius, Gudbjartsson, Daniel F., Thorleifsson, Gudmar, Sulem, Patrick, Thorsteinsdottir, Unnur, Norddahl, Gudmundur L., Jonsdottir, Ingileif, and Stefansson, Kari

Published
2020
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8. Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset

Author

Saevarsdottir, Saedis, Stefansdottir, Lilja, Sulem, Patrick, Thorleifsson, Gudmar, Ferkingstad, Egil, Rutsdottir, Gudrun, Glintborg, Bente, Westerlind, Helga, Grondal, Gerdur, Loft, Isabella C., Sorensen, Signe Bek, Lie, Benedicte A., Brink, Mikael, Arlestig, Lisbeth, Arnthorsson, Asgeir Orn, Baecklund, Eva, Banasik, Karina, Bank, Steffen, Bjorkman, Lena I, Ellingsen, Torkell, Erikstrup, Christian, Frei, Oleksandr, Gjertsson, Inger, Gudbjartsson, Daniel F., Gudjonsson, Sigurjon A., Halldorsson, Gisli H., Hendricks, Oliver, Hillert, Jan, Hogdall, Estrid, Jacobsen, Soren, Jensen, Dorte Vendelbo, Jonsson, Helgi, Kastbom, Alf, Kockum, Ingrid, Kristensen, Salome, Kristjansdottir, Helga, Larsen, Margit H., Linauskas, Asta, Hauge, Ellen-Margrethe, Loft, Anne G., Ludviksson, Bjorn R., Lund, Sigrun H., Markusson, Thorsteinn, Masson, Gisli, Melsted, Pall, Moore, Kristjan H. S., Munk, Heidi, Nielsen, Kaspar R., Norddahl, Gudmundur L., Oddsson, Asmundur, Olafsdottir, Thorunn A., Olason, Pall I, Olsson, Tomas, Ostrowski, Sisse Rye, Horslev-Petersen, Kim, Rognvaldsson, Solvi, Sanner, Helga, Silberberg, Gilad N., Stefansson, Hreinn, Sorensen, Erik, Sorensen, Inge J., Turesson, Carl, Bergman, Thomas, Alfredsson, Lars, Kvien, Tore K., Brunak, Soren, Steinsson, Kristjan, Andersen, Vibeke, Andreassen, Ole A., Rantapaa-Dahlqvist, Solbritt, Hetland, Merete Lund, Klareskog, Lars, Askling, Johan, Padyukov, Leonid, Pedersen, Ole Bv, Thorsteinsdottir, Unnur, Jonsdottir, Ingileif, Stefansson, Kari, Saevarsdottir, Saedis, Stefansdottir, Lilja, Sulem, Patrick, Thorleifsson, Gudmar, Ferkingstad, Egil, Rutsdottir, Gudrun, Glintborg, Bente, Westerlind, Helga, Grondal, Gerdur, Loft, Isabella C., Sorensen, Signe Bek, Lie, Benedicte A., Brink, Mikael, Arlestig, Lisbeth, Arnthorsson, Asgeir Orn, Baecklund, Eva, Banasik, Karina, Bank, Steffen, Bjorkman, Lena I, Ellingsen, Torkell, Erikstrup, Christian, Frei, Oleksandr, Gjertsson, Inger, Gudbjartsson, Daniel F., Gudjonsson, Sigurjon A., Halldorsson, Gisli H., Hendricks, Oliver, Hillert, Jan, Hogdall, Estrid, Jacobsen, Soren, Jensen, Dorte Vendelbo, Jonsson, Helgi, Kastbom, Alf, Kockum, Ingrid, Kristensen, Salome, Kristjansdottir, Helga, Larsen, Margit H., Linauskas, Asta, Hauge, Ellen-Margrethe, Loft, Anne G., Ludviksson, Bjorn R., Lund, Sigrun H., Markusson, Thorsteinn, Masson, Gisli, Melsted, Pall, Moore, Kristjan H. S., Munk, Heidi, Nielsen, Kaspar R., Norddahl, Gudmundur L., Oddsson, Asmundur, Olafsdottir, Thorunn A., Olason, Pall I, Olsson, Tomas, Ostrowski, Sisse Rye, Horslev-Petersen, Kim, Rognvaldsson, Solvi, Sanner, Helga, Silberberg, Gilad N., Stefansson, Hreinn, Sorensen, Erik, Sorensen, Inge J., Turesson, Carl, Bergman, Thomas, Alfredsson, Lars, Kvien, Tore K., Brunak, Soren, Steinsson, Kristjan, Andersen, Vibeke, Andreassen, Ole A., Rantapaa-Dahlqvist, Solbritt, Hetland, Merete Lund, Klareskog, Lars, Askling, Johan, Padyukov, Leonid, Pedersen, Ole Bv, Thorsteinsdottir, Unnur, Jonsdottir, Ingileif, and Stefansson, Kari

Abstract

Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce., Funding Agencies|NORDFORSK [90825]; Swedish Research Council [2018-02803]; Swedish innovation Agency (Vinnova); Innovationsfonden; The Research Council of Norway; Region Stockholm-Karolinska Institutet; Region Vasterbotten (ALF); Danish Rheumatism Association [R194-A6956, A1923, A3037, A3570]; Swedish Brain Foundation; Nils and Bibbi Jensens Foundation; Knut and Alice Wallenberg Foundation; Margaretha af Ugglas Foundation; South-Eastern Heath Region of Norway; Health Research Fund of Central Denmark Region; Region of Southern Denmark; A.P. Moller Foundation for the Advancement of Medical Science; Colitis-Crohn Foreningen; Novo Nordisk Foundation [NNF15OC0016932]; Aase og Ejnar Danielsens Fond; Beckett-Fonden; Augustinus Fonden; Knud and Edith Eriksens Mindefond; Laege Sofus Carl Emil Friis and Hustru Olga Doris Friis Legat; Psoriasis Forskningsfonden; University of Aarhus; Region of Southern Denmarks PhD Fund [12/7725]; Department of Rheumatology, Frederiksberg Hospital; Research Council of Norway [229624, 223273]; South East and Western Norway Health Authorities; ERC AdG project SELECTionPREDISPOSED; Stiftelsen Kristian Gerhard Jebsen; Trond Mohn Foundation; Novo Nordisk Foundation; University of Bergen

Published
2022
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10. Detailed Multiplex Analysis of SARS-CoV-2 Specific Antibodies in COVID-19 Disease

Author

Brynjolfsson, Siggeir F., primary, Sigurgrimsdottir, Hildur, additional, Einarsdottir, Elin D., additional, Bjornsdottir, Gudrun A., additional, Armannsdottir, Brynja, additional, Baldvinsdottir, Gudrun E., additional, Bjarnason, Agnar, additional, Gudlaugsson, Olafur, additional, Gudmundsson, Sveinn, additional, Sigurdardottir, Sigurveig T., additional, Love, Arthur, additional, Kristinsson, Karl G., additional, and Ludviksson, Bjorn R., additional

Published
2021
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15. Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

Author

Pouessel, Guillaume, Claverie, Claire, Labreuche, Julien, Renaudin, Jean-Marie, Dorkenoo, Aimée, Eb, Mireille, Moneret-Vautrin, Anne, Deschildre, Antoine, Leteurtre, Stephane, Grabenhenrich, Linus, Worm, Margitta, Dölle, Sabine, Scherer, Kathrin, Hutteger, Isidor, Christensen, Morten, Bindslev-Jensen, Carsten, Mortz, Charlotte, Eller, Esben, Kjaer, Henrik F, Carneiro-Leão, Leonor, Badas, Jenny, Coimbra, Alice, Levy, Dikla P, Ben-Shoshan, Moshe, Rimon, Ayelet, Benor, Shira, Arends, Nicolette J T, Edelbroek, Nikki, de Groot, Hans, Emons, Joyce A M, Brand, H. K A, Verhoeven, Dirk, van Veen, Leonieke N, de Jong, Nicolette W, Noh, Geunwoong, Jang, Eun H, Pascal, Mariona, Dominguez, Olga, Piquer, Mònica, Alvaro, Montserrat, Jimenez-Feijoo, Rosa, Lozano, Jaime, Machinena, Adriana, del Mar Folqué, Maria, Giner, Maria T, Plaza, Ana M, Turner, Paul, Patel, Nandinee, Vazquez-Ortiz, Marta, Lindsley, Sarah, Walker, Lucy, Rosenberg, Simon, Mari, Adriano, Alessandri, Claudia, Giangrieco, Ivana, Tuppo, Lisa, Rafaiani, Chiara, Mitterer, Georg, Ciancamerla, Michela, Ferrara, Rosetta, Bernardi, Maria L, Zennaro, Danila, Tamburrini, Maurizio, Ciardiello, Maria A, Harwanegg, Christian, Fernandez, Antonio, Selb, Regina, Egenmann, Philippe, Epstein, Michelle, Hoffmann-Sommergruber, Karin, Koning, Frits, Lovik, Martinus, Clare Mills, E. N, Moreno, Javier, van Loveren, Henk, Wal, Jean-Michel, Diesner, Susanne, Bergmayr, Cornelia, Pfitzner, Barbara, Assmann, Vera E, Starkl, Philipp, Endesfelder, David, Eiwegger, Thomas, Szepfalusi, Zsolt, Fehrenbach, Heinz, Jensen-Jarolim, Erika, Hartmann, Anton, Pali-Schöll, Isabella, Untersmayr, Eva, Wille, Soren, Meyer, Peter, Klingebiel, Caroline, Lidholm, Jonas, Ehrenberg, Angelica, Östling, Jonas, Cleach, Isabelle, Mège, Jean-Louis, Vitte, Joana, Aina, Roberta, Dubiela, Pawel, Pfeifer, Sabine, Bublin, Merima, Radauer, Christian, Humeniuk, Piotr, Kabasser, Stefan, Asero, Riccardo, Bogas, Gador, Gomez, Francisca, Campo, Paloma, Salas, Maria, Doña, Inmaculada, Barrionuevo, Esther, Guerrero, Maria A, Mayorga, Cristobalina, Prieto, Ana, Barber, Domingo, Torres, Maria J, Jamin, Annette, Wangorsch, Andrea, Ballmer, Barbara, Vieths, Stefan, Scheurer, Stephan, Apostolovic, Danijela, Mihailovic, Jelena, Krstic, Maja, Starkhammar, Maria, Velickovic, Tanja C, Hamsten, Carl, van Hage, Marianne, van Erp, Francine C, Knol, Edward F, Kansen, Hannah M, Pontoppidan, Bo, Meijer, Yolanda, van der Ent, Cornelis K, Knulst, André C, Sayers, Rebekah, Brown, Helen, Custovic, Adnan, Simpson, Angela, Mills, Claire, Schulz, Juliane, Akkerdaas, Jaap, Totis, Muriel, Capt, Annabelle, Herouet-Guicheney, Corinne, van Ree, Ronald, Banerjee, Tushar, Banerjee, Antima, Claude, Mathilde, Bouchaud, Grégory, Lupi, Roberta, Castan, Laure, Tranquet, Olivier, Denery-Papini, Sandra, Bodinier, Marie, Brossard, Chantal, De Poi, Rosella, Gritti, Elisa, De Dominicis, Emiliano, Popping, Bert, de Laureto, Patrizia P, Palosuo, Kati, Kukkonen, Anna K, Pelkonen, Anna, Mäkelä, Mika, Lee, Nanju A, Rost, Johanna, Muralidharan, Sridevi, Campbell, Dianne, Mehr, Sam, Nock, Catherine, Baumert, Joseph, Taylor, Steve, Mastrorilli, Carla, Tripodi, Salvatore, Caffarelli, Carlo, Perna, Serena, Di Rienzo Businco, Andrea, Sfika, Ifigenia, Dondi, Arianna, Bianchi, Annamaria, Dascola, Carlotta P, Ricci, Giampaolo, Cipriani, Francesca, Maiello, Nunzia, del Giudice, Michele M, Frediani, Tullio, Frediani, Simone, Macrì, Francesco, Pistoletti, Chiara, Iacono, Iride D, Patria, Maria F, Varin, Elena, Peroni, Diego, Comberiati, Pasquale, Chini, Loredana, Moschese, Viviana, Lucarelli, Sandra, Bernardini, Roberto, Pingitore, Giuseppe, Pelosi, Umberto, Olcese, Roberta, Moretti, Matteo, Cirisano, Anastasia, Faggian, Diego, Travaglini, Alessandro, Plebani, Mario, Verga, Maria C, Calvani, Mauro, Giordani, Paolo, Matricardi, Paolo M, Ontiveros, Noe, Cabrera-Chavez, Francisco, Galand, Julie, Beaudouin, Etienne, Pineau, Florence, Sakai, Shinobu, Matsunaga, Kayoko, Teshima, Reiko, Larré, Colette, Denery, Sandra, Tschirner, Sebastian, Trendelenburg, Valérie, Schulz, Gabriele, Niggemann, Bodo, Beyer, Kirsten, Bouferkas, Youcef, Belabbas, Younes, Saidi, Djamel, Kheroua, Omar, Mecherfi, Kamel E E, Guendouz, Malika, Haddi, Abir, Kaddouri, Hanane, Amaral, Luis, Pereira, Ana, Rodrigues, Susana, Datema, Mareen, Jongejan, Laurian, Clausen, Michael, Knulst, Andre, Papadopoulos, Nikolaos, Kowalski, Marek, de Blay, Frédéric, Zwinderman, Aeilko, Hoffman-Sommergruber, Karin, Ballmer-Weber, Barbara, Fernandez-Rivas, Montserrat, Deng, Shan, Yin, Jia, Eisenmann, Charlotte, Nassiri, Maria, Reinert, Rabea, van der Valk, Johanna P M, van Wijk, Roy G, Vergouwe, Yvonne, Steyerberg, Ewout W, Reitsma, Marit, Wichers, Harry J, Savelkoul, Huub F J, Vlieg-Boerstra, Berber, Dubois, Anthony E J, Carolino, Fabrícia, Rodolfo, Ana, Cernadas, Josefina, Roa-Medellín, Dasha, Rodriguez-Fernandez, Ana, Navarro, Joaquín, Albendiz, Vicente, Baeza, María L, Intente-Herrero, Sonsoles, Mikkelsen, Andrea, Mehlig, Kirsten, Lissner, Lauren, Verrill, Linda, Luccioli, Stefano, van Bilsen, Jolanda, Kuper, Frieke, Wolterbeek, André, Rankouhi, Tanja R, Verschuren, Lars, Cnossen, Hilde, Jeurink, Prescilla, Garssen, Johan, Knippels, Léon, Garthoff, Jossie, Houben, Geert, Leeman, Winfried, Eleonore Pettersson, M., Schins, Afke M M, Koppelman, Gerard H, Kollen, Boudewjin J, Zubchenko, Svitlana, Kuntz, Sarah, Mérida, Pablo, Álvaro, Montserrat, Piquer, Monica, Riggioni, Carmen, Castellanos, Juan H, Jimenez, Rosa, Cap, Melanie, Drumez, Elodie, Lejeune, Stéphanie, Thumerelle, Caroline, Mordacq, Clémence, Nève, Véronique, Ricò, Sonia, Varini, Margherita, Nocerino, Rita, Cosenza, Linda, Amoroso, Antonio, Di Costanzo, Margherita, Di Scala, Carmen, Bedogni, Giorgio, Canani, Roberto B, Turner, Paul J, Poza-Guedes, Paloma, González-Pérez, Ruperto, Sánchez-Machín, Inmaculada, Matheu-Delgado, Victor, Wambre, Erik, Ballegaard, Anne-Sofie, Madsen, Charlotte, Gregersen, Juliane, Bøgh, Katrine L, Aubert, Philippe, Neunlist, Michel, Magnan, Antoine, Lozano-Ojalvo, Daniel, Pablos-Tanarro, Alba, Pérez-Rodríguez, Leticia, Molina, Elena, López-Fandiño, Rosina, Rekima, Akila, Macchiaverni, Patricia, Turfkruyer, Mathilde, Holvoet, Sebastien, Dupuis, Lénaïck, Baiz, Nour, Annesi-Maesano, Isabella, Mercenier, Annick, Nutten, Sophie, Verhasselt, Valérie, Mrakovcic-Sutic, Ines, Banac, Srdan, Sutic, Ivana, Baricev-Novakovic, Zdenka, Sutic, Ingrid, Pavisic, Valentino, Muñoz-Cano, Rosa, Jiménez-Rodríguez, Teodoríkez, Corbacho, Daniel, Roca-Ferrer, Jordi, Bartra, Joan, Bulog, Aleksandar, Micovic, Vladimir, Markiewicz, Lidia, Szymkiewicz, Agata, Szyc, Anna, Wróblewska, Barbara, Harvey, Bryan M, Harthoorn, Lucien F, Wesley Burks, A., Rentzos, Georgios, Björk, Anna-Lena B, Bengtsson, Ulf, Barber, Colin, Kalicinsky, Chrystyna, Breynaert, Christine, Coorevits, Lieve, Jansen, Cornelia, Van Hoeyveld, Erna, Verbeke, Kristin, Kochuyt, Anne-Marie, Schrijvers, Rik, Deleanu, Diana, Muntean, Adriana, Konstantakopoulou, Maria, Pasioti, Maria, Papadopoulou, Anastasia, Iliopoulou, Anna, Mikos, Nikolaos, Kompoti, Evangelia, de Castro, Eunice D, Bartalomé, Borja, Ue, Kok L, Griffiths, Elizabeth, Till, Stephen, Grimshaw, Kate, Roberts, Graham, Selby, Anna, Butiene, Indre, Larco, Jose I, Dubakiene, Ruta, Fiandor, Ana, Fiocchi, Alessandro, Papadopoulos, Nikos, Sigurdardottir, Sigurveig, Sprikkelman, Aline, Schoemaker, Anne-Fleur, Xepapadaki, Paraskevi, Keil, Thomas, Cojocariu, Zizi, Barbado, Beatriz S, Iancu, Vasti, Arroabarren, Esozia, Esarte, Marta G, Arteaga, Miren, Andrade, Mayra C, Borges, Denise, Kalil, Jorge, Bianchi, Pedro G, Agondi, Rosana C, Gupta, Rinkesh K, Sharma, Akanksha, Gupta, Kriti, Das, Mukul, Dwivedi, Premendra, Karseladze, Rusudan, Jorjoliani, Liana, Saginadze, Lali, Tskhakaia, Mariam, Basello, Katia, Piuri, Gabriele, Speciani, Attilio F, Speciani, Michela C, Camerotto, Carla, Zinno, Francesco, Pakholchuk, Olga, Nedelska, Svitlana, Pattini, Stefano, Costantino, Maria T, Peveri, Silvia, Villalta, Danilo, Savi, Eleonora, Costanzi, Andrea, Revyakina, Vera A, Kiseleva, Marina A, Kuvshinova, Elena D, Larkova, Inna A, Shekhetov, Anton A, Silva, Diana, Moreira, André, Plácido, José, van der Kleij, Hanneke, van Twuijver, Esther, Sutorius, Robbert, de Kam, Pieter-Jan, van Odijk, Jenny, Lindqvist, Helen, Lustig, Elin, Jácome, Amyra A A, Aguilar, Karla L B, Domínguez, Miguel G, Hernández, David A M, Caruso, Cristiano, Casale, Cono, Rapaccini, Gian L, Romano, Antonino, De Vitis, Italo, Cocco, Renata R, Aranda, Carolina, Mallozi, Marcia C, Motta, Jackeline F, Moraes, Lilian, Pastorino, Antonio, Rosario, Nelson, Goudouris, Ekaterini, Porto, Arnaldo, Wandalsen, Neusa F, Sarinho, Emanuel, Sano, Flavio, Solé, Dirceu, Pitsios, Constantinos, Petrodimopoulou, Maria, Papadopoulou, Ekaterini, Passioti, Maria, Kontogianni, Meropi, Adamia, Nino, Khaleva, Ekaterina, del Prado, Ana P, Du Toit, George, Krzych, Edyta, Samolinska-Zawisza, Urszula, Furmanczyk, Konrad, Tomaszewska, Aneta, Raciborski, Filip, Lipiec, Agnieszka, Samel-Kowalik, Piotr, Walkiewicz, Artur, Borowicz, Jacek, Samolinski, Boleslaw, Nano, Aimee L, Recto, Marysia, Somoza, Maria L, López, Natalia B, Alzate, Diana P, Ruano, Francisco J, Garcimartín, Maria I, Haroun, Elisa, de la Torre, Maria V, Rojas, Antonia, Onieva, Montserrat L, 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Canto, Gabriela, Rodrigues, Alexandra, Forno, Andreia, Cabral, António J, Gonçalves, Rute, Vorozhko, Ilya, Sentsova, Tatyana, Chernyak, Olga, Denisova, Svetlana, Ilènko, Lidia, Muhortnich, Valery, Zimmermann, Caroline, Rohrbach, Alexander, Bakhsh, Faisal R, Boudewijn, Kollen, Oomkes-Pilon, Anne-Marie, Van Ginkle, Dorien, Šilar, Mira, Jeverica, Anja, Vesel, Tina, Avčin, Tadej, Korošec, Peter, van der Valk, Johanna, Berends, Irene, Arends, Nicolette, van Maaren, Maurits, Wichers, Harry, Emons, Joyce, Dubois, Anthony, de Jong, Nicolette, Matsyura, Oksana, Besh, Lesya, Huang, Chung-Hsiung, Jan, Tong-Rong, Stiefel, Gary, Tratt, Jean, Kirk, Kerrie, Carolino, Fabricia, Arasi, Stefania, Caminiti, Lucia, Crisafulli, Giuseppe, Fiamingo, Chiara, Fresta, Jlenia, Pajno, Giovanni, Remington, Ben, Kruizinga, Astrid, Marty Blom, W., Westerhout, Joost, Bijlsma, Sabina, Baumert, Joe, Blankestijn, Mark, Otten, Henny, Klemans, Rob, Michelsen-Huisman, Anouska D, van Os-Medendorp, Harmieke, Kruizinga, Astrid G, Versluis, Astrid, van Duijn, Gert, de Zeeuw-Brouwer, H. M, Castenmiller, Jacqueline J M, Noteborn, Hub P J M, Houben, Geert F, Bravin, Kristian, Luyt, David, Javed, Bushra, Couch, Phil, Munro, Christopher, Padfield, Phil, Sperrin, Matt, Byrne, Aideen, Oosthuizen, Lizalet, Kelleher, Carina, Ward, Fiona, Brosnan, Niamh, King, Graham, Corbet, Eva, Guzmán, Josué A H, García, Montserrat B, Asensio, Oscar, Navarrete, Laura V, Larramona, Helena, Miró, Xavier D, Pyrz, Katarzyna, Austin, Moira, Boloh, Yanne, Couch, Philip, Galloway, Deirdre, Hernandez, Pilar, Hourihane, Jonathan O, Kenna, Fiona, Majkowska-Wojciechowska, Barbara, Regent, Lynne, Themisb, Marina, Schnadt, Sabine, Semic-Jusufagic, Aida, Galvin, Audrey D, Kauppila, Tiina, Kuitunen, Mikael, Kitsioulis, Nikolaos A, Douladiris, Nikolaos, Kostoudi, Sofia, Manolaraki, Ioanna, Mitsias, Dimitris, Manousakis, Emmanouil, Papadopoulos, Nikolaos G, Knibb, Rebecca, Hammond, Jennifer, Cooke, Richard, Yrjänä, Jaakko, Hanni, Anna-Maija, Vähäsarja, Päivi, Mustonen, Oona, Dunder, Teija, Kulmala, Petri, Lasa, Eva, D’Amelio, Carmen, Martínez, Sara, Joral, Alejandro, Gastaminza, Gabriel, Goikoetxea, Maria J, Candy, David C A, Van Ampting, Marleen T J, Oude Nijhuis, Manon M, Butt, Assad M, Peroni, Diego G, Fox, Adam T, Knol, Jan, Michaelis, Louise J, Padua, Ines, Padrao, Patricia, Moreira, Pedro, Barros, Renata, Sharif, Hanan, Ahmed, Manzoor, Gomaa, Nehad, Mens, Joris, Smit, Koen, Timmermans, Frans, Poredoš, Tomaž, Jeverica, Anja K, Sedmak, Marjeta, Benedik, Evgen, Accetto, Meta, Zupančič, Mirjana, Yonamine, Glauce, Soldateli, Gustavo, Aquilante, Bruna, Pastorino, Antonio C, de Moraes Beck, Cleonir L, Gushken, Andrea K, de Barros Dorna, Mayra, dos Santos, Cristiane N, Castro, Ana P M, Al-Qahtani, Abdulhadi, Arnaout, Rand, Khaliq, Agha R, Amin, Rashid, Sheikh, Farrukh, Alvarez, Jorge, Anda, Marta, Palacios, Miriam, De Prada, Montserrat, Ponce, Carmen, Balbino, Bianca, Sibilano, Riccardo, Marichal, Thomas, Gaudenzio, Nicolas, Karasuyama, Hajime, Bruhns, Pierre, Tsai, Mindy, Reber, Laurent L, Galli, Stephen J, Ferreira, Ana R, Cernadas, Josefina R, del Campo García, Aida, Fernández, Sara P, Carrera, Nerea S, Sánchez-Cruz, Fernando B, Lorenzo, José R F, Claus, Stephanie, Pföhler, Claudia, Ruëff, Franziska, Treudler, Regina, Jaume, Mercedes E, Madroñero, Agustin, Perez, Maria T G, Julia, Juan C, Plovdiv, Charlotte H, Gethings, Lee, Langridge, Jim, Adel-Patient, Karine, Bernard, Hervé, Barcievic-Jones, Ivona, Sokolova, Raditsa, Yankova, Rumyana, Ivanovska, Mariya, Murdjeva, Marianna, Popova, Tatyana, Dermendzhiev, Svetlan, Karjalainen, Martin, Lehnigk, Ulrike, Brown, Duncan, Locklear, Julie C, Locklear, Julie, Maris, Ioana, Hourihane, Jonathan, Ornelas, Cristina, Caiado, Joana, Ferreira, Manuel B, Pereira-Barbosa, Manuel, Puente, Yolanda, Daza, Juan C, Monteseirin, Francisco J, Ukleja-Sokolowska, Natalia, Gawronska-Ukleja, Ewa, Zbikowska-Gotz, Magdalena, Bartuzi, Zbigniew, Sokolowski, Lukasz, Adams, Aine, Mahon, Bernard, English, Karen, Gourdon-Dubois, Nelly, Sellam, Laetitia, Pereira, Bruno, Michaud, Elodie, Messaoudi, Khaled, Evrard, Bertrand, Fauquert, Jean-Luc, Palomares, Francisca, Gomez, Gador, Rodriguez, Maria J, Galindo, Luisa, Molina, Ana, Paparo, Lorella, Mennini, Maurizio, Aitoro, Rosita, Wawrzeńczyk, Adam, Przybyszewski, Michał, Wawrzeńczyk, Anna, Sarıcoban, Hulya E, Ugras, Meltem, Yalvac, Zerrin, Flokstra-de Blok, Bertine M J, van der Velde, J. L, Vereda, Andrea, Ippolito, Clara, Traversa, Amaranta, Adriano, Daniela, Bianchi, Daniela M, Gallina, Silvia, Decastelli, Lucia, Makatsori, Melina, Miles, Anne, Devetak, Sonja P, Devetak, Iztok, Tabet, Soraya A, Trandbohus, Jeanette F, Winther, Pernille, Malling, Hans-Jørgen, Hansen, Kirsten S, Garvey, Lene H, Wang, Chia-Chi, Cheng, Yin-Hua, Tung, Chun-Wei, Dietrich, Mariola, Marenholz, Ingo, Kalb, Birgit, Grosche, Sarah, Blümchen, Katharina, Schlags, Rupert, Price, Mareike, Rietz, Sylke, Esparza-Gordillo, Jorge, Lau, Susanne, Lee, Young-Ae, Almontasheri, Ali, Bahkali, Mohammad A, Elshorbagi, Sahar, Alfhaid, Abdullah, Altamimi, Mashary, Madbouly, Eman, Al-Dhekri, Hassan, Arnaout, Rand K, Basagaña, Maria, Miquel, Sira, Bartolomé, Borja, Brix, Bettina, Rohwer, Stefanie, Brandhoff, Sandra, Berger, Alena, Suer, Waltraud, Weimann, Alf, Bueno, Cristina, Martín-Pedraza, Laura, Abián, Sara, Segundo-Acosta, Pablo S, López-Rodríguez, Juan C, Barderas, Rodrigo, Batanero, Eva, Cuesta-Herranz, Javier, Villalba, María T, Correia, Magna, Benito-Garcia, Filipe, Arêde, Cristina, Piedade, Susana, Morais-Almeida, Mário, Hindley, James, Yarham, Ross, Kuklinska-Pijanka, Anna, Gillick, David, Patient, Karine, Chapman, Martin D, Miranda, Ana, Matos, Eugénia, Sokolova, Anna, Rao, Huan, Baricevic-Jones, Ivona, Smith, Frances, Xue, Wentong, Magnusdottir, Helga, Vidarsdottir, Anna G, Lund, Sigrun, Jensen, Anders B, Ludviksson, Bjorn R, Simon, Reyna, Elfont, Robert, Bennett, Sean, Voyksner, Robert, de Lurdes Torre, Maria, Yürek, Songül, Faber, Margaretha A, Bastiaensen, Annick, Mangodt, Evelyne, van Gasse, Athina, Decuyper, Ine, Sabato, Vito, Hagendorens, Margo M, Bridts, Chris H, De Clerck, Luc S, Ebo, Didier, Schwarz, Susanne, Ziegert, Mandy, Albroscheit, Saskia, Schwager, Christian, Kull, Skadi, Behrends, Jochen, Röckendorf, Niels, Schocker, Frauke, Frey, Andreas, Homann, Arne, Becker, Wolf-Meinhard, Jappe, Uta, Zaabat, Nesrine, Osscini, Sylvia, Agabriel, Chantal, Sterling, Benoît, Carsin, Ania, Liabeuf, Valérie, Maćków, Monica, Zbróg, Alina, Bronkowska, Monica, Courtois, Justine, Gadisseur, Romy, Bertholet, Catherine, Lukas, Pierre, Cavalier, Etienne, Delahaut, Philippe, Quinting, Birgit, Gertmo, Margareta B, Hasseus, Ewa T, Barzylovych, Vladyslava, Oliveira, Júlio, Ensina, Luis F, Aranda, Carolina S, Dopazo, Leire, Lopez, Rebeca, Perez, Raquel, Santos-Diez, Laura, Bilbao, Agurtzane, Garcia, Juan M, Núñez, Ignacio G, Mármol, María Á A, Villarejo, María J B, Martos, José A B, Vergara, Marina S, García, José M I, Michalska, Agata, Sergiejko, Grzegorz, Zacniewski, Robert, Ghiordanescu, Ileana-Maria, Deaconu, Cristina, Popescu, Mihaela, Bumbacea, Roxana S, Ibranji, Alkerta, Nikolla, Elida, Loloci, Gjustina, Juel-Berg, Nanna, Larsen, Lau F, Poulsen, Lars K, Marcelino, João, Prata, Ricardo, Costa, Ana C, Duarte, Fátima, Neto, Marta, Santos, Jennifer, Pestana, Luís C, Sampaio, Daniel, Minale, Paola, Dignetti, Paola, Bignardi, Donatella, Nedelea, Irena, Popescu, Florin-Dan, Vieru, Mariana, Secureanu, Florin-Adrian, Ganea, Carmen S, Vieira, Miguel, Silva, José P M, Watts, Timothy, Watts, Sophia, Lomikovska, Marta, Peredelskaya, Marina, Nenasheva, Natalia, Filipovic, Ivana, Zivkovic, Zorica, Filipovic, Djordje, Higgs, Jennette, Warner, Amena, and Jones, Carla

Published
2017

16. Identification of sequence variants influencing immunoglobulin levels

Author

Jonsson, Stefan, primary, Sveinbjornsson, Gardar, additional, de Lapuente Portilla, Aitzkoa Lopez, additional, Swaminathan, Bhairavi, additional, Plomp, Rosina, additional, Dekkers, Gillian, additional, Ajore, Ram, additional, Ali, Mina, additional, Bentlage, Arthur E H, additional, Elmér, Evelina, additional, Eyjolfsson, Gudmundur I, additional, Gudjonsson, Sigurjon A, additional, Gullberg, Urban, additional, Gylfason, Arnaldur, additional, Halldorsson, Bjarni V, additional, Hansson, Markus, additional, Holm, Hilma, additional, Johansson, Åsa, additional, Johnsson, Ellinor, additional, Jonasdottir, Aslaug, additional, Ludviksson, Bjorn R, additional, Oddsson, Asmundur, additional, Olafsson, Isleifur, additional, Olafsson, Sigurgeir, additional, Sigurdardottir, Olof, additional, Sigurdsson, Asgeir, additional, Stefansdottir, Lilja, additional, Masson, Gisli, additional, Sulem, Patrick, additional, Wuhrer, Manfred, additional, Wihlborg, Anna-Karin, additional, Thorleifsson, Gudmar, additional, Gudbjartsson, Daniel F, additional, Thorsteinsdottir, Unnur, additional, Vidarsson, Gestur, additional, Jonsdottir, Ingileif, additional, Nilsson, Björn, additional, and Stefansson, Kari, additional

Published
2017
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17. FLT3stop mutation increases FLT3 ligand level and risk of autoimmune thyroid disease

Author

Saevarsdottir, Saedis, Olafsdottir, Thorunn A., Ivarsdottir, Erna V., Halldorsson, Gisli H., Gunnarsdottir, Kristbjorg, Sigurdsson, Asgeir, Johannesson, Ari, Sigurdsson, Jon K., Juliusdottir, Thorhildur, Lund, Sigrun H., Arnthorsson, Asgeir O., Styrmisdottir, Edda L., Gudmundsson, Julius, Grondal, Gerdur M., Steinsson, Kristjan, Alfredsson, Lars, Askling, Johan, Benediktsson, Rafn, Bjarnason, Ragnar, Geirsson, Arni J., Gudbjornsson, Bjorn, Gudjonsson, Hallgrimur, Hjaltason, Haukur, Hreidarsson, Astradur B., Klareskog, Lars, Kockum, Ingrid, Kristjansdottir, Helga, Love, Thorvardur J., Ludviksson, Bjorn R., Olsson, Tomas, Onundarson, Pall T., Orvar, Kjartan B., Padyukov, Leonid, Sigurgeirsson, Bardur, Tragante, Vinicius, Bjarnadottir, Kristbjorg, Rafnar, Thorunn, Masson, Gisli, Sulem, Patrick, Gudbjartsson, Daniel F., Melsted, Pall, Thorleifsson, Gudmar, Norddahl, Gudmundur L., Thorsteinsdottir, Unnur, Jonsdottir, Ingileif, and Stefansson, Kari

Abstract

Autoimmune thyroid disease is the most common autoimmune disease and is highly heritable1. Here, by using a genome-wide association study of 30,234 cases and 725,172 controls from Iceland and the UK Biobank, we find 99 sequence variants at 93 loci, of which 84 variants are previously unreported2–7. A low-frequency (1.36%) intronic variant in FLT3(rs76428106-C) has the largest effect on risk of autoimmune thyroid disease (odds ratio (OR) = 1.46, P= 2.37 × 10−24). rs76428106-C is also associated with systemic lupus erythematosus (OR = 1.90, P= 6.46 × 10−4), rheumatoid factor and/or anti-CCP-positive rheumatoid arthritis (OR = 1.41, P= 4.31 × 10−4) and coeliac disease (OR = 1.62, P= 1.20 × 10−4). FLT3encodes fms-related tyrosine kinase 3, a receptor that regulates haematopoietic progenitor and dendritic cells. RNA sequencing revealed that rs76428106-C generates a cryptic splice site, which introduces a stop codon in 30% of transcripts that are predicted to encode a truncated protein, which lacks its tyrosine kinase domains. Each copy of rs76428106-C doubles the plasma levels of the FTL3 ligand. Activating somatic mutations in FLT3are associated with acute myeloid leukaemia8with a poor prognosis and rs76428106-C also predisposes individuals to acute myeloid leukaemia (OR = 1.90, P= 5.40 × 10−3). Thus, a predicted loss-of-function germline mutation in FLT3causes a reduction in full-length FLT3, with a compensatory increase in the levels of its ligand and an increased disease risk, similar to that of a gain-of-function mutation.

Published
2020
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18. A loss-of-function variant in ALOX15protects against nasal polyps and chronic rhinosinusitis

Author

Kristjansson, Ragnar P., Benonisdottir, Stefania, Davidsson, Olafur B., Oddsson, Asmundur, Tragante, Vinicius, Sigurdsson, Jon K., Stefansdottir, Lilja, Jonsson, Stefan, Jensson, Brynjar O., Arthur, Joseph G., Arnadottir, Gudny A., Sulem, Gerald, Halldorsson, Bjarni V., Gunnarsson, Bjarni, Halldorsson, Gisli H., Stefansson, Olafur A., Oskarsson, Gudjon R., Deaton, Aimee M., Olafsson, Isleifur, Eyjolfsson, Gudmundur I., Sigurdardottir, Olof, Onundarson, Pall T., Gislason, David, Gislason, Thorarinn, Ludviksson, Bjorn R., Ludviksdottir, Dora, Olafsdottir, Thorunn A., Rafnar, Thorunn, Masson, Gisli, Zink, Florian, Bjornsdottir, Gyda, Magnusson, Olafur Th., Bjornsdottir, Unnur S., Thorleifsson, Gudmar, Norddahl, Gudmundur L., Gudbjartsson, Daniel F., Thorsteinsdottir, Unnur, Jonsdottir, Ingileif, Sulem, Patrick, and Stefansson, Kari

Abstract

Nasal polyps (NP) are lesions on the nasal and paranasal sinus mucosa and are a risk factor for chronic rhinosinusitis (CRS). We performed genome-wide association studies on NP and CRS in Iceland and the UK (using UK Biobank data) with 4,366 NP cases, 5,608 CRS cases, and >700,000 controls. We found 10 markers associated with NP and 2 with CRS. We also tested 210 markers reported to associate with eosinophil count, yielding 17 additional NP associations. Of the 27 NP signals, 7 associate with CRS and 13 with asthma. Most notably, a missense variant in ALOX15that causes a p.Thr560Met alteration in arachidonate 15-lipoxygenase (15-LO) confers large genome-wide significant protection against NP (P=8.0 × 10−27, odds ratio = 0.32; 95% confidence interval = 0.26, 0.39) and CRS (P=1.1 × 10−8, odds ratio = 0.64; 95% confidence interval = 0.55, 0.75). p.Thr560Met, carried by around 1 in 20 Europeans, was previously shown to cause near total loss of 15-LO enzymatic activity. Our findings identify 15-LO as a potential target for therapeutic intervention in NP and CRS.

Published
2019
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21. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

Author

Gudbjartsson, Daniel F., Bjornsdottir, Unnur S., Halapi, Eva, Helgadottir, Anna, Sulem, Patrick, Jonsdottir, Gudrun M., Thorleifsson, Gudmar, Helgadottir, Hafdis, Steinthorsdottir, Valgerdur, Stefansson, Hreinn, Williams, Carolyn, Hui, Jennie, Beilby, John, Warrington, Nicole M., James, Alan, Palmer, Lyle J., Koppelman, Gerard H., Heinzmann, Andrea, Krueger, Marcus, Boezen, H. Marike, Wheatley, Amanda, Altmuller, Janine, Shin, Hyoung Doo, Uh, Soo-Taek, Cheong, Hyun Sub, Jonsdottir, Brynja, Gislason, David, Park, Choon-Sik, Rasmussen, Linda M., Porsbjerg, Celeste, Hansen, Jakob W., Backer, Vibeke, Werge, Thomas, Janson, Christer, Jönsson, Ulla-Britt, Ng, Maggie C. Y., Chan, Juliana, So, Wing Yee, Ma, Ronald, Shah, Svati H., Granger, Christopher B., Quyyumi, Arshed A., Levey, Allan I., Vaccarino, Viola, Reilly, Muredach P., Rader, Daniel J., Williams, Michael J. A., van Rij, Andre M., Jones, Gregory T., Trabetti, Elisabetta, Malerba, Giovanni, Pignatti, Pier Franco, Boner, Attilio, Pescollderungg, Lydia, Girelli, Domenico, Olivieri, Oliviero, Martinelli, Nicola, Ludviksson, Bjorn R., Ludviksdottir, Dora, Eyjolfsson, Gudmundur I., Arnar, David, Thorgeirsson, Gudmundur, Deichmann, Klaus, Thompson, Philip J., Wjst, Matthias, Hall, Ian P., Postma, Dirkje S., Gislason, Thorarinn, Gulcher, Jeffrey, Kong, Augustine, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, Stefansson, Kari, Gudbjartsson, Daniel F., Bjornsdottir, Unnur S., Halapi, Eva, Helgadottir, Anna, Sulem, Patrick, Jonsdottir, Gudrun M., Thorleifsson, Gudmar, Helgadottir, Hafdis, Steinthorsdottir, Valgerdur, Stefansson, Hreinn, Williams, Carolyn, Hui, Jennie, Beilby, John, Warrington, Nicole M., James, Alan, Palmer, Lyle J., Koppelman, Gerard H., Heinzmann, Andrea, Krueger, Marcus, Boezen, H. Marike, Wheatley, Amanda, Altmuller, Janine, Shin, Hyoung Doo, Uh, Soo-Taek, Cheong, Hyun Sub, Jonsdottir, Brynja, Gislason, David, Park, Choon-Sik, Rasmussen, Linda M., Porsbjerg, Celeste, Hansen, Jakob W., Backer, Vibeke, Werge, Thomas, Janson, Christer, Jönsson, Ulla-Britt, Ng, Maggie C. Y., Chan, Juliana, So, Wing Yee, Ma, Ronald, Shah, Svati H., Granger, Christopher B., Quyyumi, Arshed A., Levey, Allan I., Vaccarino, Viola, Reilly, Muredach P., Rader, Daniel J., Williams, Michael J. A., van Rij, Andre M., Jones, Gregory T., Trabetti, Elisabetta, Malerba, Giovanni, Pignatti, Pier Franco, Boner, Attilio, Pescollderungg, Lydia, Girelli, Domenico, Olivieri, Oliviero, Martinelli, Nicola, Ludviksson, Bjorn R., Ludviksdottir, Dora, Eyjolfsson, Gudmundur I., Arnar, David, Thorgeirsson, Gudmundur, Deichmann, Klaus, Thompson, Philip J., Wjst, Matthias, Hall, Ian P., Postma, Dirkje S., Gislason, Thorarinn, Gulcher, Jeffrey, Kong, Augustine, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, and Stefansson, Kari

Abstract

Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).

Published
2009
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22. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

Author

Gudbjartsson, Daniel F, Bjornsdottir, Unnur S, Halapi, Eva, Helgadottir, Anna, Sulem, Patrick, Jonsdottir, Gudrun M, Thorleifsson, Gudmar, Helgadottir, Hafdis, Steinthorsdottir, Valgerdur, Stefansson, Hreinn, Williams, Carolyn, Hui, Jennie, Beilby, John, Warrington, Nicole M, James, Alan, Palmer, Lyle J, Koppelman, Gerard H, Heinzmann, Andrea, Krueger, Marcus, Boezen, H Marike, Wheatley, Amanda, Altmuller, Janine, Shin, Hyoung Doo, Uh, Soo-Taek, Cheong, Hyun Sub, Jonsdottir, Brynja, Gislason, David, Park, Choon-Sik, Rasmussen, Linda M, Porsbjerg, Celeste, Hansen, Jakob W, Backer, Vibeke, Werge, Thomas, Janson, Christer, Jönsson, Ulla-Britt, Ng, Maggie C Y, Chan, Juliana, So, Wing Yee, Ma, Ronald, Shah, Svati H, Granger, Christopher B, Quyyumi, Arshed A, Levey, Allan I, Vaccarino, Viola, Reilly, Muredach P, Rader, Daniel J, Williams, Michael J A, van Rij, Andre M, Jones, Gregory T, Trabetti, Elisabetta, Malerba, Giovanni, Pignatti, Pier Franco, Boner, Attilio, Pescollderungg, Lydia, Girelli, Domenico, Olivieri, Oliviero, Martinelli, Nicola, Ludviksson, Bjorn R, Ludviksdottir, Dora, Eyjolfsson, Gudmundur I, Arnar, David, Thorgeirsson, Gudmundur, Deichmann, Klaus, Thompson, Philip J, Wjst, Matthias, Hall, Ian P, Postma, Dirkje S, Gislason, Thorarinn, Gulcher, Jeffrey, Kong, Augustine, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, Stefansson, Kari, Gudbjartsson, Daniel F, Bjornsdottir, Unnur S, Halapi, Eva, Helgadottir, Anna, Sulem, Patrick, Jonsdottir, Gudrun M, Thorleifsson, Gudmar, Helgadottir, Hafdis, Steinthorsdottir, Valgerdur, Stefansson, Hreinn, Williams, Carolyn, Hui, Jennie, Beilby, John, Warrington, Nicole M, James, Alan, Palmer, Lyle J, Koppelman, Gerard H, Heinzmann, Andrea, Krueger, Marcus, Boezen, H Marike, Wheatley, Amanda, Altmuller, Janine, Shin, Hyoung Doo, Uh, Soo-Taek, Cheong, Hyun Sub, Jonsdottir, Brynja, Gislason, David, Park, Choon-Sik, Rasmussen, Linda M, Porsbjerg, Celeste, Hansen, Jakob W, Backer, Vibeke, Werge, Thomas, Janson, Christer, Jönsson, Ulla-Britt, Ng, Maggie C Y, Chan, Juliana, So, Wing Yee, Ma, Ronald, Shah, Svati H, Granger, Christopher B, Quyyumi, Arshed A, Levey, Allan I, Vaccarino, Viola, Reilly, Muredach P, Rader, Daniel J, Williams, Michael J A, van Rij, Andre M, Jones, Gregory T, Trabetti, Elisabetta, Malerba, Giovanni, Pignatti, Pier Franco, Boner, Attilio, Pescollderungg, Lydia, Girelli, Domenico, Olivieri, Oliviero, Martinelli, Nicola, Ludviksson, Bjorn R, Ludviksdottir, Dora, Eyjolfsson, Gudmundur I, Arnar, David, Thorgeirsson, Gudmundur, Deichmann, Klaus, Thompson, Philip J, Wjst, Matthias, Hall, Ian P, Postma, Dirkje S, Gislason, Thorarinn, Gulcher, Jeffrey, Kong, Augustine, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, and Stefansson, Kari

Abstract

Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).

Published
2009

24. A sequence variant on 17q21 is associated with age at onset and severity of asthma

Author

Halapi, Eva, primary, Gudbjartsson, Daniel F, additional, Jonsdottir, Gudrun M, additional, Bjornsdottir, Unnur S, additional, Thorleifsson, Gudmar, additional, Helgadottir, Hafdis, additional, Williams, Carolyn, additional, Koppelman, Gerard H, additional, Heinzmann, Andrea, additional, Boezen, H Marike, additional, Jonasdottir, Aslaug, additional, Blondal, Thorarinn, additional, Gudjonsson, Sigurjon A, additional, Jonasdottir, Adalbjorg, additional, Thorlacius, Theodora, additional, Henry, Amanda P, additional, Altmueller, Janine, additional, Krueger, Marcus, additional, Shin, Hyoung Doo, additional, Uh, Soo-Taek, additional, Cheong, Hyun Sub, additional, Jonsdottir, Brynja, additional, Ludviksson, Bjorn R, additional, Ludviksdottir, Dora, additional, Gislason, David, additional, Park, Choon-Sik, additional, Deichmann, Klaus, additional, Thompson, Philip J, additional, Wjst, Matthias, additional, Hall, Ian P, additional, Postma, Dirkje S, additional, Gislason, Thorarinn, additional, Kong, Augustine, additional, Jonsdottir, Ingileif, additional, Thorsteinsdottir, Unnur, additional, and Stefansson, Kari, additional

Published
2010
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27. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

Author

Gudbjartsson, Daniel F, primary, Bjornsdottir, Unnur S, additional, Halapi, Eva, additional, Helgadottir, Anna, additional, Sulem, Patrick, additional, Jonsdottir, Gudrun M, additional, Thorleifsson, Gudmar, additional, Helgadottir, Hafdis, additional, Steinthorsdottir, Valgerdur, additional, Stefansson, Hreinn, additional, Williams, Carolyn, additional, Hui, Jennie, additional, Beilby, John, additional, Warrington, Nicole M, additional, James, Alan, additional, Palmer, Lyle J, additional, Koppelman, Gerard H, additional, Heinzmann, Andrea, additional, Krueger, Marcus, additional, Boezen, H Marike, additional, Wheatley, Amanda, additional, Altmuller, Janine, additional, Shin, Hyoung Doo, additional, Uh, Soo-Taek, additional, Cheong, Hyun Sub, additional, Jonsdottir, Brynja, additional, Gislason, David, additional, Park, Choon-Sik, additional, Rasmussen, Linda M, additional, Porsbjerg, Celeste, additional, Hansen, Jakob W, additional, Backer, Vibeke, additional, Werge, Thomas, additional, Janson, Christer, additional, Jönsson, Ulla-Britt, additional, Ng, Maggie C Y, additional, Chan, Juliana, additional, So, Wing Yee, additional, Ma, Ronald, additional, Shah, Svati H, additional, Granger, Christopher B, additional, Quyyumi, Arshed A, additional, Levey, Allan I, additional, Vaccarino, Viola, additional, Reilly, Muredach P, additional, Rader, Daniel J, additional, Williams, Michael J A, additional, van Rij, Andre M, additional, Jones, Gregory T, additional, Trabetti, Elisabetta, additional, Malerba, Giovanni, additional, Pignatti, Pier Franco, additional, Boner, Attilio, additional, Pescollderungg, Lydia, additional, Girelli, Domenico, additional, Olivieri, Oliviero, additional, Martinelli, Nicola, additional, Ludviksson, Bjorn R, additional, Ludviksdottir, Dora, additional, Eyjolfsson, Gudmundur I, additional, Arnar, David, additional, Thorgeirsson, Gudmundur, additional, Deichmann, Klaus, additional, Thompson, Philip J, additional, Wjst, Matthias, additional, Hall, Ian P, additional, Postma, Dirkje S, additional, Gislason, Thorarinn, additional, Gulcher, Jeffrey, additional, Kong, Augustine, additional, Jonsdottir, Ingileif, additional, Thorsteinsdottir, Unnur, additional, and Stefansson, Kari, additional

Published
2009
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30. Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset.

Author

Saevarsdottir S, Stefansdottir L, Sulem P, Thorleifsson G, Ferkingstad E, Rutsdottir G, Glintborg B, Westerlind H, Grondal G, Loft IC, Sorensen SB, Lie BA, Brink M, Ärlestig L, Arnthorsson AO, Baecklund E, Banasik K, Bank S, Bjorkman LI, Ellingsen T, Erikstrup C, Frei O, Gjertsson I, Gudbjartsson DF, Gudjonsson SA, Halldorsson GH, Hendricks O, Hillert J, Hogdall E, Jacobsen S, Jensen DV, Jonsson H, Kastbom A, Kockum I, Kristensen S, Kristjansdottir H, Larsen MH, Linauskas A, Hauge EM, Loft AG, Ludviksson BR, Lund SH, Markusson T, Masson G, Melsted P, Moore KHS, Munk H, Nielsen KR, Norddahl GL, Oddsson A, Olafsdottir TA, Olason PI, Olsson T, Ostrowski SR, Hørslev-Petersen K, Rognvaldsson S, Sanner H, Silberberg GN, Stefansson H, Sørensen E, Sørensen IJ, Turesson C, Bergman T, Alfredsson L, Kvien TK, Brunak S, Steinsson K, Andersen V, Andreassen OA, Rantapää-Dahlqvist S, Hetland ML, Klareskog L, Askling J, Padyukov L, Pedersen OB, Thorsteinsdottir U, Jonsdottir I, and Stefansson K

Subjects
Genetic Predisposition to Disease genetics, Humans, Interferon-alpha, Janus Kinases genetics, Protein Tyrosine Phosphatase, Non-Receptor Type 22 genetics, Proteomics, STAT Transcription Factors genetics, Signal Transduction genetics, Arthritis, Rheumatoid genetics, Genome-Wide Association Study
Abstract

Objectives: To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets., Methods: We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and ~1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen)., Results: We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4 -variants, increases the risk of seropositive RA 2.27-fold (p=2.1×10 -9 ), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3×10 -160 ). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6×10 -11 ). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10 -9 -10 -27 ) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4., Conclusion: Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce., Competing Interests: Competing interests: Authors affiliated with deCODE Genetics/Amgen declare competing financial interests as employees. OAA is a consultant to HealthLytix. The following coauthors report the following but unrelated to the current report: Karolinska Institutet, with JA as principal investigator, has entered into agreements with the following entities, mainly but not exclusively for safety monitoring of rheumatology immunomodulators: Abbvie, BMS, Eli Lilly, Janssen, MSD, Pfizer, Roche, Samsung Bioepis and Sanofi, unrelated to the present study. SB has ownerships in Intomics A/S, Hoba Therapeutics Aps, Novo Nordisk A/S, Lundbeck A/S and managing board memberships in Proscion A/S and Intomics A/S. BG has received research grants from AbbVie, Bristol Myers-Squibb and Pfizer; OH has received research grants from AbbVie, Novartis and Pfizer, DVJ has received speaker and consultation fees from AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, AGL has received speaking and/or consulting fees from AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB; and CT has received consulting fees from Roche, speaker fees from Abbvie, Bristol Myers-Squibb, Nordic Drugs, Pfizer and Roche, and an unrestricted grant from Bristol Myers-Squibb., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2022
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