@article{3147033,
    title = "A Large-Scale, Consortium-Based Genomewide Association Study of Asthma",
    author = "Moffatt, Miriam F. and Gut, Ivo G. and Demenais, Florence and Strachan, and David P. and Bouzigon, Emmanuelle and Heath, Simon and von Mutius, Erika and and Farrall, Martin and Lathrop, Mark and Cookson, William O. C. M. and and Kumar, Ashish and Burney, Peter and Jarvis, Debbie and Wjst, Matthias and and Kogevinas, Manolis and Jogi, Rain and Janson, Christer and Franklin, and Karl A. and Omenaas, Ernst and Leynaert, Benedicte and Pin, Isabelle and and Heinrich, Joachim and Probst-Hensch, Nicole M. and Anto, Josep M. and and Sunyer, Jordi and Maldonado, Jose-Antonio and Martinez-Moratalla, Jesus and and Urrutia, Isabel and Payo, Felix and Kauffmann, Francine and Dizier, and Marie-Helene and Siroux, Valerie and Boznanski, Andrzej and and Braun-Fahrlaender, Charlotte and Genuneit, Jon and Glas, Juergen and and Horak, Elisabeth and Kabesch, Michael and Pillai, Sreekumar G. and and Helms, Peter J. and Carlsen, Karin and Carlsen, Kai-Hakon and Gerritsen, and Jorrit and Silverman, Michael and Sly, Peter and Tsanakas, John and Von and Berg, Andrea and Whyte, Moira and Blumenthal, Malcolm and Imboden, Medea and and Rochat, Thierry and Thun, Gian Andri and Gerbase, Margaret W. and and Curjuric, Ivan and Gaspoz, Jean-Michel and Liu, Lee-Jane S. and Wouters, and Inge M. and Sigsgaard, Torben and Heederik, Dick and Basinas, Ioannis and and Schlunssen, Vivi and Omland, Oyvind and Cullinan, Paul and and Vermeulen, Roel and Henderson, John and Granell, Raquel and McArdle, and Wendy L. and Smith, George Davey and James, Alan L. and Hui, Jennie and and Palmer, Lyle J. and Beilby, John and Musk, A. William and Laprise, and Catherine and Hudson, Thomas J. and Lemire, Mathieu and Daley, Denise and and Becker, Allan and Chan-Yeung, Moira and Sandford, Andrew and and Kozyrskyj, Anita L. and Pare, Peter and Ferguson, Alexander and and Dimich-Ward, Helen and Watson, Wade T. and Freidin, Maxim B. and and Bragina, Elena Iu. and Deev, Ivan A. and Deeva, Eugenia V. and and Kobyakova, Olga S. and Puzyrev, Valery P. and Ogorodova, Ludmila M. and and Khusnutdinova, Elza K. and Karunas, Alexandra S. and Fedorova, Yuliya Y. and and Hall, Ian P. and Sayers, Ian and Tobin, Martin D. and Wan, Yize I. and and Heaney, Liam G. and Al-Momani, Basima A. H. and Mansur, Adel H. and and Manney, Sarah and Thomson, Neil C. and Chaudhuri, Rekha and Brightling, and Christopher E. and Bafadhel, Mona and Singapuri, Amisha and Niven, and Robert and Simpson, Angela and Holloway, John W. and Howarth, Peter H. and and Polonikov, Alexey V. and Ivanov, Vladimir P. and Solodilova, Maria and A. and Melen, Erik and Pershagen, Goeran and Bergstroem, Anna and Kull, and Inger and Nyberg, Fredrik and Wickman, Magnus and Soderhall, Cilla and and Kere, Juha and Postma, Dirkje S. and Kerkhof, Marjan and Brunekreef, and Bert and Smit, Henriette A. and de Jongste, Johan C. and Wijga, Alet and and Aalberse, R. C. and Hoekstra, Maarten O. and Koppelman, Gerard H. and and Binia, Aristea and Chung, Kian Fan and Bhavsar, Pankaj and Chow, and Florence and Macedo, Patricia and Menzies-Gow, Andrew and van Stiphout, and Nicole and Bush, Andrew and Lee, Young-Ae and Esparza-Gordillo, Jorge and and Nickel, Renate and Wahn, Ulrich and Lau, Susanne and Marenholz, Ingo and and Haahtela, Tari and von Hertzen, Leena and Jousilahti, Pekka and and Laatikainen, Tiina and Makela, Mika J. and Vartiainen, Erkki and and Laitinen, Tarja and Balding, David J. and Peden, John F. and Corda, Eve and and Lechner, Doris and Besse, Celine and Zelenika, Diana and Boland, and Anne and Bacq, Delphine and Demonchy, Stephanie and Blanche, Helene and and Kamatani, Yoichiro and von Mutius, Erika and Farrall, Martin and and Lathrop, Mark and Cookson, William O. C. M. and GABRIEL Consortium",
    journal = "The New England journal of medicine",
    year = "2010",
    volume = "363",
    number = "13",
    pages = "1211-1221",
    publisher = "MASSACHUSETTS MEDICAL SOC",
    doi = "10.1056/NEJMoa0906312",
    abstract = "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."
}