| Autor: |
Moffatt, Miriam F. Gut, Ivo G. Demenais, Florence Strachan, David P. Bouzigon, Emmanuelle Heath, Simon von Mutius, Erika and Farrall, Martin Lathrop, Mark Cookson, William O. C. M. and Kumar, Ashish Burney, Peter Jarvis, Debbie Wjst, Matthias and Kogevinas, Manolis Jogi, Rain Janson, Christer Franklin, Karl A. Omenaas, Ernst Leynaert, Benedicte Pin, Isabelle and Heinrich, Joachim Probst-Hensch, Nicole M. Anto, Josep M. and Sunyer, Jordi Maldonado, Jose-Antonio Martinez-Moratalla, Jesus and Urrutia, Isabel Payo, Felix Kauffmann, Francine Dizier, Marie-Helene Siroux, Valerie Boznanski, Andrzej and Braun-Fahrlaender, Charlotte Genuneit, Jon Glas, Juergen and Horak, Elisabeth Kabesch, Michael Pillai, Sreekumar G. and Helms, Peter J. Carlsen, Karin Carlsen, Kai-Hakon Gerritsen, Jorrit Silverman, Michael Sly, Peter Tsanakas, John Von Berg, Andrea Whyte, Moira Blumenthal, Malcolm Imboden, Medea and Rochat, Thierry Thun, Gian Andri Gerbase, Margaret W. and Curjuric, Ivan Gaspoz, Jean-Michel Liu, Lee-Jane S. Wouters, Inge M. Sigsgaard, Torben Heederik, Dick Basinas, Ioannis and Schlunssen, Vivi Omland, Oyvind Cullinan, Paul and Vermeulen, Roel Henderson, John Granell, Raquel McArdle, Wendy L. Smith, George Davey James, Alan L. Hui, Jennie and Palmer, Lyle J. Beilby, John Musk, A. William Laprise, Catherine Hudson, Thomas J. Lemire, Mathieu Daley, Denise and Becker, Allan Chan-Yeung, Moira Sandford, Andrew and Kozyrskyj, Anita L. Pare, Peter Ferguson, Alexander and Dimich-Ward, Helen Watson, Wade T. Freidin, Maxim B. and Bragina, Elena Iu. Deev, Ivan A. Deeva, Eugenia V. and Kobyakova, Olga S. Puzyrev, Valery P. Ogorodova, Ludmila M. and Khusnutdinova, Elza K. Karunas, Alexandra S. Fedorova, Yuliya Y. and Hall, Ian P. Sayers, Ian Tobin, Martin D. Wan, Yize I. and Heaney, Liam G. Al-Momani, Basima A. H. Mansur, Adel H. and Manney, Sarah Thomson, Neil C. Chaudhuri, Rekha Brightling, Christopher E. Bafadhel, Mona Singapuri, Amisha Niven, Robert Simpson, Angela Holloway, John W. Howarth, Peter H. and Polonikov, Alexey V. Ivanov, Vladimir P. Solodilova, Maria A. Melen, Erik Pershagen, Goeran Bergstroem, Anna Kull, Inger Nyberg, Fredrik Wickman, Magnus Soderhall, Cilla and Kere, Juha Postma, Dirkje S. Kerkhof, Marjan Brunekreef, Bert Smit, Henriette A. de Jongste, Johan C. Wijga, Alet and Aalberse, R. C. Hoekstra, Maarten O. Koppelman, Gerard H. and Binia, Aristea Chung, Kian Fan Bhavsar, Pankaj Chow, Florence Macedo, Patricia Menzies-Gow, Andrew van Stiphout, Nicole Bush, Andrew Lee, Young-Ae Esparza-Gordillo, Jorge and Nickel, Renate Wahn, Ulrich Lau, Susanne Marenholz, Ingo and Haahtela, Tari von Hertzen, Leena Jousilahti, Pekka and Laatikainen, Tiina Makela, Mika J. Vartiainen, Erkki and Laitinen, Tarja Balding, David J. Peden, John F. Corda, Eve and Lechner, Doris Besse, Celine Zelenika, Diana Boland, Anne Bacq, Delphine Demonchy, Stephanie Blanche, Helene and Kamatani, Yoichiro von Mutius, Erika Farrall, Martin and Lathrop, Mark Cookson, William O. C. M. GABRIEL Consortium |
| Jazyk: |
angličtina |
| Rok vydání: |
2010 |
| Popis: |
BACKGROUND Susceptibility to asthma is influenced by genes and environment; implicated genes may indicate pathways for therapeutic intervention. Genetic risk factors may be useful in identifying subtypes of asthma and determining whether intermediate phenotypes, such as elevation of the total serum IgE level, are causally linked to disease. METHODS We carried out a genomewide association study by genotyping 10,365 persons with physician-diagnosed asthma and 16,110 unaffected persons, all of whom were matched for ancestry. We used random-effects pooled analysis to test for association in the overall study population and in subgroups of subjects with childhood-onset asthma (defined as asthma developing before 16 years of age), later-onset asthma, severe asthma, and occupational asthma. RESULTS We observed associations of genomewide significance between asthma and the following single-nucleotide polymorphisms: rs3771166 on chromosome 2, implicating IL1RL1/IL18R1 (P = 3x10(-9)); rs9273349 on chromosome 6, implicating HLA-DQ (P = 7x10(-14)); rs1342326 on chromosome 9, flanking IL33 (P = 9x10(-10)); rs744910 on chromosome 15 in SMAD3 (P = 4x10(-9)); and rs2284033 on chromosome 22 in IL2RB (P = 1.1x10(-8)). Association with the ORMDL3/GSDMB locus on chromosome 17q21 was specific to childhood-onset disease (rs2305480, P = 6x10(-23)). Only HLA-DR showed a significant genomewide association with the total serum IgE concentration, and loci strongly associated with IgE levels were not associated with asthma. CONCLUSIONS Asthma is genetically heterogeneous. A few common alleles are associated with disease risk at all ages. Implicated genes suggest a role for communication of epithelial damage to the adaptive immune system and activation of airway inflammation. Variants at the ORMDL3/GSDMB locus are associated only with childhood-onset disease. Elevation of total serum IgE levels has a minor role in the development of asthma. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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