Original Article
A Large-Scale, Consortium-Based Genomewide Association Study of Asthma
N Engl J Med 2010; 363:1211-1221September 23, 2010
- 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=3×10−9); rs9273349 on chromosome 6, implicating HLA-DQ (P=7×10−14); rs1342326 on chromosome 9, flanking IL33 (P=9×10−10); rs744910 on chromosome 15 in SMAD3 (P=4×10−9); and rs2284033 on chromosome 22 in IL2RB (P=1.1×10−8). Association with the ORMDL3/GSDMB locus on chromosome 17q21 was specific to childhood-onset disease (rs2305480, P=6×10−23). 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. (Funded by the European Commission and others.)
Media in This Article
Figure 1
Manhattan Plot of Study Results.Figure 2
Forest Plots of Odds Ratios for Markers with Genomewide Association with Asthma According to Study Subgroup.Article Activity
- Article
Asthma is a syndrome of unknown origins that is characterized by abnormal and inflamed mucosa of the airways, wheezing, and shortness of breath. In some patients, irreversible airway remodeling and intractable airflow limitation may develop. The disease has a high prevalence and a chronic relapsing course. Although some effective therapies exist for mild asthma, severe asthma remains difficult to treat. The societal cost of the disease is substantial.1,2
Asthma runs strongly in families, and its heritability has been estimated as 60%.3 Genetic studies offer a structured means of understanding the causes of asthma as well as identifying targets that can be used to treat the syndrome.
Childhood asthma is more common in boys than in girls and may persist throughout life. It is often associated with atopy, and as a consequence, much of the research into asthma has focused on atopic mechanisms.4 However, the link between atopic sensitization and asthma symptoms in children is absent in many populations,5 calling into question a causal role of IgE production in the disease. Adult-onset asthma typically develops in middle age and is more common in women than in men. It is less obviously associated with allergy and may be resistant to treatment. Occupational asthma results from workplace exposure to dusts or chemicals and is the most common occupational lung disease in the European Community.
An adequately powered genomewide association study is currently the method of choice for identifying genes that influence complex disease.6 The GABRIEL (A Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community) Consortium conducted a previous, comparatively small genomewide association study, which showed that multiple markers on chromosome 17q21 were strongly and reproducibly associated with childhood-onset asthma.7,8 We report here the results of a genomewide association study conducted with a sample 10 times the size of that used in our first-generation study. In addition to reporting on analyses of childhood-onset asthma, we report on analyses of later-onset and occupational asthma. Genetic studies can determine whether disease-related phenotypes cause the disease or result from it.9,10 Consequently, we wanted to determine whether there was a concordance between single-nucleotide polymorphisms (SNPs) associated with asthma and SNPs associated with total serum IgE levels. We also wanted to ascertain the extent to which the genetic variants that we observed to be associated with asthma determine the individual risk of asthma development, and we modeled the effects these variants have on the burden of disease in the populations we studied.
Methods
Subjects
The study consisted of 10,365 case subjects and 16,110 controls recruited from 23 studies (Table 1Table 1
Subjects and Populations in Studies of Patients with Asthma Onset in Childhood or Later or with Unknown Age at Onset.; and the Supplementary Appendix, available with the full text of this article at NEJM.org). Data on case subjects and population-matched controls were obtained from clinics and from cohort and cross-sectional population surveys in Europe (Table 1 in the Supplementary Appendix). We included some subjects from family-based studies, case subjects and controls from our first-generation genomewide association study,7 and case subjects and controls of European descent from Canadian, Australian, and U.S. surveys. Asthma was considered to be present if it had been diagnosed by a physician. We defined childhood-onset asthma as the presence of the disease in a person younger than 16 years of age and later-onset asthma as disease that developed at 16 years of age or older. Some surveys contributed samples to both age-at-onset groups. Other subgroups consisted of subjects with asthma that developed at an unknown age, subjects with occupational asthma, and subjects with severe asthma (for details, see the Supplementary Appendix). All participants or their parents provided written informed consent for their participation in the study, in accordance with the rules of local ethics committees. The study was performed in accordance with the protocol.Genotyping
We genotyped 582,892 SNPs for each subject, producing approximately 15 billion genotypes. See the Supplementary Appendix for a description of the handling of DNA and for further details on genotyping.
Statistical Analysis
The study was well powered to detect variants with an allele frequency of 10% and an odds ratio greater than 1.20 or those with an allele frequency of 45% and an odds ratio greater than 1.10. See the Supplementary Appendix for a detailed description of the statistical analyses.
After filtering the genotypes for quality, we controlled for population admixture using principal-components analysis for case subjects and controls in individual populations, removing any outliers. The principal-components analysis for European studies showed good discrimination of country of origin (Figure 1 in the Supplementary Appendix), including subjects from multicenter studies such as the European Community Respiratory Health Survey. The mean genomic control parameter after principal-components analysis was 1.02 (range, 1.01 to 1.05).
Results
Associations with Asthma
We examined the full sample of persons with asthma (including subjects for whom age at onset was unknown and those with occupational asthma or severe asthma) and controls (Figure 1Figure 1
Manhattan Plot of Study Results. and Table 2Table 2
Loci with Genomewide Significance for Asthma and Tests of Heterogeneity across Studies., and Table 1 in the Supplementary Appendix). The full set of results is available at www.cng.fr/gabriel, and the results and data have been deposited in the European Genome–Phenome Archive (EGA) at the European Bioinformatics Institute (accession number, EGAS00000000077). We also tested for association among subjects with childhood-onset asthma (6783 case subjects and 7720 controls) and those with later-onset asthma (1947 case subjects and 3669 controls) (Table 2 and Figure 2Figure 2Forest Plots of Odds Ratios for Markers with Genomewide Association with Asthma According to Study Subgroup., and Table 1 and Table 2 in the Supplementary Appendix). We then examined loci with genomewide significance in the full sample in the subgroups of subjects with occupational asthma and those with severe asthma (these samples were too small to justify full genomewide analyses) (Table 1 in the Supplementary Appendix). We identified loci with genomewide significance in the overall sample on chromosomes 2, 6, 9, 15, 17, and 22 (Figure 1 and Table 2, and Table 1 in the Supplementary Appendix).The strongest association on chromosome 2 was with a SNP within the IL18R1 gene (rs3771166) (P=3.4×10−9; odds ratio, 0.87). IL18R1 is in close proximity to IL1RL1, which also contained SNPs showing significant association with asthma (Table 1 in the Supplementary Appendix); these SNPS were in high linkage disequilibrium with rs3771166 (r2=0.96 for the correlation between rs3771166 and each of the three most significant SNPs on the IL1RL1 gene). A locus centered on rs9273349 in the HLA-DQ region of the major histocompatibility complex gene (MHC) also showed strong evidence of association in the overall sample (P=7×10−14; odds ratio, 1.18). We observed significant association between disease and rs1342326 (on chromosome 9), flanking the IL33 gene (P=9×10−10; odds ratio, 1.20) (Table 2). Other SNPs showing significant association with disease were rs744910 on chromosome 15 (P=4×10−9; odds ratio, 0.89), within the SMAD3 gene, and rs2284033, within IL2RB on chromosome 22 (P=1×10−8; odds ratio, 0.89) (Table 2).
The odds ratios for these loci generally suggested more pronounced effects in childhood-onset asthma than in later-onset asthma. The HLA-DQ region was observed to have a slightly stronger association with later-onset disease (P=4×10−8; odds ratio, 1.26) than with childhood-onset disease (P=2×10−5; odds ratio, 1.14). However, none of these differences were significant (Table 2 and Figure 2, and Table 2 in the Supplementary Appendix).
The span of the SNPs associated with disease at the ORMDL3/GSDMB locus on chromosome 17q12 was approximately 380 kb (Table 2, and Table 1 in the Supplementary Appendix). As in previous studies,7,8 we observed for 17q12 SNPs significant evidence of heterogeneity between associations with childhood-onset and disease and associations with significant later-onset disease (P<0.001) (Figure 2). Significant associations were confined to childhood-onset disease (Table 1 in the Supplementary Appendix), and a separate analysis of subjects with childhood-onset disease (and controls) yielded a maximum association at rs2305480 within the GSDMB gene (P=6×10−23; odds ratio, 0.76) (Table 2). Among subjects with childhood-onset disease, forward stepwise regression established an independent association with rs3894194 within GSDMA (P=0.0015), a member of the same gene family as GSDMB, in addition to rs2305480. We found no evidence of stronger associations with haplotypes containing either or both of these two SNPs.
Using a less stringent threshold for significance (P<5×10−7), we observed association between disease and rs2073643 near SLC22A5 on chromosome 5 (P=2×10−7; odds ratio, 0.90) (Table 2). This locus is approximately 273 kb upstream of — and is independent of — the previously established IL13 locus,12 which contains a SNP (rs1295686) for which there was also evidence of association (P=1×10−7) (Table 2). We also observed association with rs11071559 within RORA on chromosome 15 (P=1×10−7; odds ratio, 0.85) (Table 2).
We did not observe any significant associations that were particular to the groups with severe or occupational asthma. We did find a suggestive association with rs1837253 on chromosome 5, situated within the TSLP gene, among patients with severe asthma in the SEVERE study (P=3×10−6; odds ratio, 0.56), but this association was not replicated among patients with severe asthma in the AUGOSA (Asthma UK Genetics of Severe Asthma) study.
Logistic-regression models for interactions between loci showed effects of only marginal significance (P=0.01) before correction for multiple comparisons; these findings are thus unlikely to be of biologic importance. We found no evidence of dominance, or interactions with sex, for any of the loci.
Associations with Total Serum IgE
We tested for association with the natural logarithm of total serum IgE levels in 7087 subjects with asthma and 7667 controls, using random-effects pooled estimates (Table 3Table 3
Peak Associations with Total Serum IgE Compared with Peak Associations with Asthma., and Figure 2 in the Supplementary Appendix), and identified one novel locus within the class II region of MHC (P=8×10−15). We also confirmed previously observed associations with markers at loci housing FCER1A, IL13, STAT6, and IL4R/IL21R 13 (Table 3, and Figure 2 in the Supplementary Appendix).The IgE-related IL13 and MHC loci showed evidence of association with asthma, albeit not at the level of genomewide significance (Table 3). Moreover, mapping of the MHC loci associated with elevated IgE levels and with asthma showed that the principal genetic effects were independent of one another — near HLA-DRB1 for elevated IgE levels and near HLA-DQB1 for asthma. Linkage disequilibrium was weak between the trait-associated markers at the two MHC loci. The HLA-DQB1 markers associated with asthma remained significantly associated with asthma after adjustment for IgE level. SNPs at the FCER1A, STAT6, and IL4R/IL21R loci were not associated with asthma.
Population Burden and Individual Risk
For each of the seven SNPs associated with childhood asthma, we assessed the individual risk in a classification analysis, using a cutoff point of 0.5 (i.e., subjects were classified as having asthma if the predicted probability of disease was ≥0.5). The sensitivity for classifying subjects as having or not having asthma was 35%, and the specificity 75%. The area under the receiver-operating-characteristic curve was 0.58 (on a scale of 0.50 to 1.00).
Estimation of the population attributable risk fraction for the joint action of the significant loci indicated that 38% (95% confidence interval [CI], 28 to 44) of cases of childhood-onset asthma were attributable to SNP combinations at these loci (representing a higher risk than that for the controls with the lowest 10% of the risk score). In an independent population-based replication sample of 517 case subjects and 3486 controls, drawn from members of the British 1958 birth cohort who were not included in the current study (details are provided at www.b58cgene.sgul.ac.uk), the same SNPs accounted for 49% (95% CI, 27 to 65) of the lifetime asthma risk (from birth to middle age). These results indicate that although the SNPs would not be effective in classifying the individual risk of asthma, the SNPs (or rather, the downstream functions of which they are markers) do have a substantial effect on the burden of asthma in the community.
We tested for significant associations with loci previously reported in studies of persons of European ancestry with asthma (including PDE4D, 14 CHI3L1, 15 DPP10, 16 GPR154 [NPSR1],17 ADAM33, 18 PHF11, 19 OPN3, 20 IRAK3, 21 PCDH1, 22 HLA-G, 23 and DENND1B 24) (Table 3 in the Supplementary Appendix). We observed associations with SNPs implicating DPP10 (P≤3×10−3), PDE4D (P≤4.7×10−3), GPR154 (P≤1×10−3), and HLA-G (P≤2×10−4), but none of these associations were significant after correction for multiple comparisons. It has been suggested that genetic determinants of lung function influence susceptibility to asthma25,26; our data do not support this hypothesis (Table 4 in the Supplementary Appendix).
Discussion
Our study identifies candidate genes in a pathway that initiates type 2 helper T-cell (Th2) inflammation in response to epithelial damage and points to other candidate genes that may act in a pathway that down-regulates airway inflammation and remodeling. Our study also shows that asthma is heterogeneous: later-onset cases are influenced more by the MHC than are childhood-onset cases, and our findings confirm a strong and specific effect of the chromosome 17q locus on childhood-onset disease.7,8 Moreover, our results show that genetics cannot easily be used to determine the individual risk of asthma.
SNPs at the chromosome 17q21 locus associated with asthma are also strongly associated with variation in the expression of ORMDL3 7 and GSDMB,27,28 meaning that it is feasible that the locus contributes to asthma through the differential regulation of both genes. Changes in the expression of the homologous ORM gene in yeast cause dysregulation of sphingolipid metabolism.29 Evidence that similar pathways are involved in humans would provide a potential mechanism (and therapeutic target) for the modulation of airway inflammation.30
The association between SNPs flanking IL33 on chromosome 9 and atopic asthma has been reported previously.31 IL33 was originally detected in airway epithelial cells.32 It activates nuclear factor κB (NF-κB) and mitogen-activated protein (MAP) kinases and drives production of Th2-associated cytokines32 such as interleukin-4, interleukin-5, and interleukin-13. It is detected in inflamed tissues.33 IL33 is constitutively expressed in endothelial and epithelial cells and may function as an endogenous danger signal (an “alarmin”) to alert the immune system of epithelial damage during trauma or infection.34
The locus at chromosome 2, implicating IL1RL1 and IL18R1, has also previously been shown to be associated with asthma.31 The effect at this locus has been attributed to IL1RL1 (encoding the receptor for interleukin-33), but we were not able to dissect the association to the extent of being able to clearly implicate IL1RL1 over IL18R1. IL18 is closely related to IL33 32 and synergizes with IL12 to induce the production of interferon-γ and to promote Th1 responses.35 The expression of IL18R1 is also concentrated within the respiratory epithelium.
SMAD3 is a transcriptional modulator activated by transforming growth factor β, a polypeptide that controls proliferation, differentiation, and other functions in many cell types, including regulatory T cells.36 Mice deficient in Smad3 have increased levels of proinflammatory cytokines in their lungs.37
IL2 controls the survival and proliferation of regulatory T cells and is implicated in the differentiation and homeostasis of effector T-cell subgroups, including Th1, Th2, Th17, and memory CD8+ T cells.38 The interleukin-2 receptor is composed of α (CD25), β (CD122), and γ chains.38 The β chain (interleukin-2 receptor β [RB]) identified in our study is a signal-transduction element that is also present in the interleukin-15 receptor. Thus, the IL33 and IL18R1 loci may modify the inflammatory response to epithelial damage, whereas SMAD3 and IL2RB may regulate homeostatic and healing pathways.
HLA-DQ was the first asthma-susceptibility locus to be identified,39 and extended haplotypes encompassing HLA-DQ and HLA-DR have been studied for their effects on specific allergen sensitization40,41 and on the formation of tumor necrosis factor and related gene products.42 Our results indicate that HLA-DQ may be fundamental to later-onset disease. Adult-onset asthma is thought to have a minor atopic component; HLA-DQ may restrict the response to bacterial or other antigens that do not act as classical allergens in these patients.
Suggestive data point to two other genes, SLC22A5 and RORA. SLC22A5 encodes a carnitine transporter and, like ORMDL3/GSDMB and IL18R1/IL1RL1, sports variants that are associated with Crohn's disease.43 Asthma and Crohn's disease may therefore have shared mechanisms, perhaps involving a modulation of microbial interactions with the mucosa. RORA encodes a member of the NR1 subfamily of nuclear hormone receptors. It is expressed at high levels in keratinocytes, together with a cluster of genes that form the structural and innate immune defenses of the epithelial barrier.44
We found little overlap between the principal loci that confer susceptibility to asthma and those that regulate total serum IgE levels, with the exception of IL13 and the HLA region (which contains multiple loci affecting these phenotypes). This suggests that elevation of the IgE level is probably an inconstant secondary effect of asthma rather than its cause, a conclusion that is consistent with the absence of a relationship between atopic sensitization and asthma in many populations.5 Genetic studies of children with atopic dermatitis have shown that defects in barrier proteins such as Flaggrin (FLG)45 and the serine protease inhibitor SPINK546 commonly confer a predisposition to the disease, indicating that increases in IgE levels may be the result of barrier failure.
Many loci have been reported to have an association with asthma47; most of these associations were not significant in our well-powered study. The relative risks observed with our markers will not be useful as predictors of disease in individual patients, no doubt because of variable environmental effects. These loci nevertheless contribute substantially to the asthma burden in the general population. Further studies are needed to identify the specific genetic variants that contribute to disease and to establish their biologic function. Such studies may help to identify the causes of airway epithelial damage that initiate the asthmatic process. In the mean time, ORMDL3 and GSDMB, IL33 and IL1RL1, IL18R1, SMAD3, and IL2RB already provide a focus in the search for more effective therapies for asthma.
Supported by a contract from the European Commission (018996) and grants from the French Ministry of Research, the Wellcome Trust (WT084703MA), and Asthma UK.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
Drs. Moffatt, Gut, and Demenais contributed equally to this article.
We thank Dana Finch, GABRIEL project manager, for her administrative support of the study and the GABRIEL Consortium.
Source Information
From the National Heart and Lung Institute, Imperial College (M.F.M., W.O.C.M.C.), the Division of Community Health Sciences, St. George's, University of London (D.P.S.), and Royal Brompton and Harefield NHS Foundation Trust (W.O.C.M.C.) — all in London; Commissariat à l'Energie Atomique, Institut de Génomique, Centre National de Génotypage, Evry, France (I.G.G., S.H., M.L.); INSERM, Unité 946, Fondation Jean-Dausset–Centre d'Etude du Polymorphisme Humain (CEPH) (F.D., E.B.), Fondation Jean Dausset–CEPH (F.D., E.B., M.L.), and Université Paris Diderot Paris 7, Institut Universitaire d'Hématologie (F.D., E.B.) — all in Paris; University Children's Hospital, Asthma and Allergy Department, Ludwig Maximilians University, Munich, Germany (E.M.); and Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom (M.F.).
Address reprint requests to Dr. Cookson at Imperial College London, Royal Brompton Campus, Guy Scadding Bldg., Dovehouse St., London SW3 6LY, United Kingdom, or at w.cookson@imperial.ac.uk.
Members of the GABRIEL (A Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community) Consortium are listed in the Supplementary Appendix, available at NEJM.org.
- References
References
1
Smith DH ,Malone DC ,Lawson KA ,Okamoto LJ ,Battista C ,Saunders WB . A national estimate of the economic costs of asthma. Am J Respir Crit Care Med 1997;156:787-793
Web of Science | Medline2
Asthma agenda. London: National Asthma Campaign, 1998.
3
Duffy DL ,Martin NG ,Battistutta D ,Hopper JL ,Mathews JD . Genetics of asthma and hay fever in Australian twins. Am Rev Respir Dis 1990;142:1351-1358
Web of Science | Medline4
Kay AB . Allergy and allergic diseases: first of two parts. N Engl J Med 2001;344:30-37
Full Text | Web of Science | Medline5
Weinmayr G ,Weiland SK ,Bjorksten B , et al. Atopic sensitization and the international variation of asthma symptom prevalence in children. Am J Respir Crit Care Med 2007;176:565-574
CrossRef | Web of Science | Medline6
Wellcome Trust Case Control Consortium
CrossRef | Web of Science | Medline7
Moffatt MF ,Kabesch M ,Liang L , et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 2007;448:470-473
CrossRef | Web of Science | Medline8
Bouzigon E ,Corda E ,Aschard H , et al. Effect of 17q21 variants and smoking exposure in early-onset asthma. N Engl J Med 2008;359:1985-1994
Full Text | Web of Science | Medline9
Sheehan NA ,Didelez V ,Burton PR ,Tobin MD . Mendelian randomisation and causal inference in observational epidemiology. PLoS Med 2008;5:e177-e177
CrossRef | Web of Science | Medline10
Elliott P ,Chambers JC ,Zhang W , et al. Genetic loci associated with C-reactive protein levels and risk of coronary heart disease. JAMA 2009;302:37-48
CrossRef | Web of Science | Medline11
Dudbridge F ,Gusnanto A . Estimation of significance thresholds for genomewide association scans. Genet Epidemiol 2008;32:227-234
CrossRef | Web of Science | Medline12
Konstantinidis AK ,Barton SJ ,Sayers I , et al. Genetic association studies of interleukin-13 receptor alpha1 subunit gene polymorphisms in asthma and atopy. Eur Respir J 2007;30:40-47
CrossRef | Web of Science | Medline13
Weidinger S ,Gieger C ,Rodriguez E , et al. Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus. PLoS Genet 2008;4:e1000166-e1000166
CrossRef | Web of Science | Medline14
Himes BE ,Hunninghake GM ,Baurley JW , et al. Genome-wide association analysis identifies PDE4D as an asthma-susceptibility gene. Am J Hum Genet 2009;84:581-593
CrossRef | Web of Science | Medline15
Ober C ,Tan Z ,Sun Y , et al. Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function. N Engl J Med 2008;358:1682-1691
Full Text | Web of Science | Medline16
Allen M ,Heinzmann A ,Noguchi E , et al. Positional cloning of a novel gene influencing asthma from chromosome 2q14. Nat Genet 2003;35:258-263
CrossRef | Web of Science | Medline17
Laitinen T ,Polvi A ,Rydman P , et al. Characterization of a common susceptibility locus for asthma-related traits. Science 2004;304:300-304
CrossRef | Web of Science | Medline18
Van Eerdewegh P ,Little RD ,Dupuis J , et al. Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature 2002;418:426-430
CrossRef | Web of Science | Medline19
Zhang Y ,Leaves NI ,Anderson GG , et al. Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma. Nat Genet 2003;34:181-186
CrossRef | Web of Science | Medline20
White JH ,Chiano M ,Wigglesworth M , et al. Identification of a novel asthma susceptibility gene on chromosome 1qter and its functional evaluation. Hum Mol Genet 2008;17:1890-1903
CrossRef | Web of Science | Medline21
Balaci L ,Spada MC ,Olla N , et al. IRAK-M is involved in the pathogenesis of early-onset persistent asthma. Am J Hum Genet 2007;80:1103-1114
CrossRef | Web of Science | Medline22
Koppelman GH ,Meyers DA ,Howard TD , et al. Identification of PCDH1 as a novel susceptibility gene for bronchial hyperresponsiveness. Am J Respir Crit Care Med 2009;180:929-935
CrossRef | Web of Science | Medline23
Nicolae D ,Cox NJ ,Lester LA , et al. Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21. Am J Hum Genet 2005;76:349-357
CrossRef | Web of Science | Medline24
Sleiman PM ,Flory J ,Imielinski M , et al. Variants of DENND1B associated with asthma in children. N Engl J Med 2010;362:36-44
Full Text | Web of Science | Medline25
Repapi E ,Sayers I ,Wain LV , et al. Genome-wide association study identifies five loci associated with lung function. Nat Genet 2010;42:36-44
CrossRef | Web of Science | Medline26
Hancock DB ,Eijgelsheim M ,Wilk JB , et al. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nat Genet 2010;42:45-52
CrossRef | Web of Science | Medline27
Cookson W ,Liang L ,Abecasis G ,Moffatt M ,Lathrop M . Mapping complex disease traits with global gene expression. Nat Rev Genet 2009;10:184-194
CrossRef | Web of Science | Medline28
Verlaan DJ ,Berlivet S ,Hunninghake GM , et al. Allele-specific chromatin remodeling in the ZPBP2/GSDMB/ORMDL3 locus associated with the risk of asthma and autoimmune disease. Am J Hum Genet 2009;85:377-393
CrossRef | Web of Science | Medline29
Breslow DK ,Collins SR ,Bodenmiller B , et al. Orm family proteins mediate sphingolipid homeostasis. Nature 2010;463:1048-1053
CrossRef | Web of Science | Medline30
Nixon GF . Sphingolipids in inflammation: pathological implications and potential therapeutic targets. Br J Pharmacol 2009;158:982-993
CrossRef | Web of Science | Medline31
Gudbjartsson DF ,Bjornsdottir US ,Halapi E , et al. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat Genet 2009;41:342-347
CrossRef | Web of Science | Medline32
Schmitz J ,Owyang A ,Oldham E , et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 2005;23:479-490
CrossRef | Web of Science | Medline33
Carriere V ,Roussel L ,Ortega N , et al. IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc Natl Acad Sci U S A 2007;104:282-287
CrossRef | Web of Science | Medline34
Moussion C ,Ortega N ,Girard JP . The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel `alarmin'? PLoS ONE 2008;3:e3331-e3331
CrossRef | Web of Science | Medline35
Fukao T ,Matsuda S ,Koyasu S . Synergistic effects of IL-4 and IL-18 on IL-12-dependent IFN-gamma production by dendritic cells. J Immunol 2000;164:64-71
Web of Science | Medline36
Nouri-Aria KT ,Durham SR . Regulatory T cells and allergic disease. Inflamm Allergy Drug Targets 2008;7:237-252
CrossRef | Medline37
Anthoni M ,Wang G ,Leino MS ,Lauerma AI ,Alenius HT ,Wolff HJ . Smad3 -signalling and Th2 cytokines in normal mouse airways and in a mouse model of asthma. Int J Biol Sci 2007;3:477-485
CrossRef | Web of Science | Medline38
Letourneau S ,Krieg C ,Pantaleo G ,Boyman O . IL-2- and CD25-dependent immunoregulatory mechanisms in the homeostasis of T-cell subsets. J Allergy Clin Immunol 2009;123:758-762
CrossRef | Web of Science | Medline39
Marsh DG ,Meyers DA ,Bias WB . The epidemiology and genetics of atopic allergy. N Engl J Med 1981;305:1551-1559
Full Text | Web of Science | Medline40
Marsh DG, Blumenthal MN, Ishikawa T, et al. HLA and specific immune responsiveness to allergens. In: Tsuji K, Aizawa M, Sazazuki T, eds. Proceedings of the Eleventh International Histocompatibility Workshop and conference. Oxford, England: Oxford University Press, 1992:765-7.
41
Moffatt MF ,Schou C ,Faux JA , et al. Association between quantitative traits underlying asthma and the HLA-DRB1 locus in a family-based population sample. Eur J Hum Genet 2001;9:341-346
CrossRef | Web of Science | Medline42
Moffatt MF ,Cookson WO . Tumour necrosis factor haplotypes and asthma. Hum Mol Genet 1997;6:551-554
CrossRef | Web of Science | Medline43
Barrett JC ,Hansoul S ,Nicolae DL , et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet 2008;40:955-962
CrossRef | Web of Science | Medline44
Taylor JM ,Street TL ,Hao L , et al. Dynamic and physical clustering of gene expression during epidermal barrier formation in differentiating keratinocytes. PLoS ONE 2009;4:e7651-e7651
CrossRef | Web of Science | Medline45
Palmer CN ,Irvine AD ,Terron-Kwiatkowski A , et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006;38:441-446
CrossRef | Web of Science | Medline46
Walley AJ ,Chavanas S ,Moffatt MF , et al. Gene polymorphism in Netherton and common atopic disease. Nat Genet 2001;29:175-178
CrossRef | Web of Science | Medline47
Vercelli D . Advances in asthma and allergy genetics in 2007. J Allergy Clin Immunol 2008;122:267-271
CrossRef | Web of Science | Medline
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Fred A Wright, Andrey A Shabalin, Ivan Rusyn. (2012) Computational tools for discovery and interpretation of expression quantitative trait loci. Pharmacogenomics 13:3, 343-352
CrossRef4
Malcolm Nolan Blumenthal. (2012) Genetic, epigenetic, and environmental factors in asthma and allergy. Annals of Allergy, Asthma & Immunology 108:2, 69-73
CrossRef5
Dara G. Torgerson, Daniel Capurso, Rasika A. Mathias, Penelope E. Graves, Ryan D. Hernandez, Terri H. Beaty, Eugene R. Bleecker, Benjamin A. Raby, Deborah A. Meyers, Kathleen C. Barnes, Scott T. Weiss, Fernando D. Martinez, Dan L. Nicolae, Carole Ober. (2012) Resequencing Candidate Genes Implicates Rare Variants in Asthma Susceptibility. The American Journal of Human Genetics 90:2, 273-281
CrossRef6
Xingnan Li, Elizabeth Ampleford, Timothy Howard, Dara Torgerson, Huashi Li, Wendy Moore, William Busse, Mario Castro, Serpil Erzurum, Anne Fitzpatrick, Benjamin Gaston, Elliot Israel, Nizar Jarjour, W. Gerald Teague, Sally Wenzel, Gregory Hawkins, Carole Ober, Dan Nicolae, Eugene R. Bleecker, Deborah Meyers. (2012) 116 Genome-Wide Association Studies of Asthma Indicate Opposite Immunopathogenesis Direction From Autoimmune Diseases. World Allergy Organization Journal 5, S38-S39
CrossRef7
K. Y. Urayama, R. F. Jarrett, H. Hjalgrim, A. Diepstra, Y. Kamatani, A. Chabrier, V. Gaborieau, A. Boland, A. Nieters, N. Becker, L. Foretova, Y. Benavente, M. Maynadie, A. Staines, L. Shield, A. Lake, D. Montgomery, M. Taylor, K. E. Smedby, R.-M. Amini, H.-O. Adami, B. Glimelius, B. Feenstra, I. M. Nolte, L. Visser, G. W. van Imhoff, T. Lightfoot, P. Cocco, L. Kiemeney, S. H. Vermeulen, I. Holcatova, L. Vatten, G. J. Macfarlane, P. Thomson, D. I. Conway, S. Benhamou, A. Agudo, C. M. Healy, K. Overvad, A. Tjonneland, B. Melin, F. Canzian, K.-T. Khaw, R. C. Travis, P. H. M. Peeters, C. A. Gonzalez, J. R. Quiros, M.-J. Sanchez, J. M. Huerta, E. Ardanaz, M. Dorronsoro, F. Clavel-Chapelon, H. B. Bueno-de-Mesquita, E. Riboli, E. Roman, P. Boffetta, S. de Sanjose, D. Zelenika, M. Melbye, A. van den Berg, M. Lathrop, P. Brennan, J. D. McKay. (2012) Genome-Wide Association Study of Classical Hodgkin Lymphoma and Epstein-Barr Virus Status-Defined Subgroups. JNCI Journal of the National Cancer Institute
CrossRef8
D. A. Cusanovich, C. Billstrand, X. Zhou, C. Chavarria, S. De Leon, K. Michelini, A. A. Pai, C. Ober, Y. Gilad. (2012) The Combination of a Genome-Wide Association Study of Lymphocyte Count and Analysis of Gene Expression Data Reveals Novel Asthma Candidate Genes. Human Molecular Genetics
CrossRef9
Soizik Berlivet, Sanny Moussette, Manon Ouimet, Dominique J. Verlaan, Vonda Koka, Abeer Al Tuwaijri, Tony Kwan, Daniel Sinnett, Tomi Pastinen, Anna K. Naumova. (2012) Interaction between genetic and epigenetic variation defines gene expression patterns at the asthma-associated locus 17q12-q21 in lymphoblastoid cell lines. Human Genetics
CrossRef10
See Heng Wong, Jennifer A Walker, Helen E Jolin, Lesley F Drynan, Emily Hams, Ana Camelo, Jillian L Barlow, Daniel R Neill, Veera Panova, Ute Koch, Freddy Radtke, Clare S Hardman, You Yi Hwang, Padraic G Fallon, Andrew N J McKenzie. (2012) Transcription factor RORα is critical for nuocyte development. Nature Immunology
CrossRef11
E. Lefrancais, S. Roga, V. Gautier, A. Gonzalez-de-Peredo, B. Monsarrat, J.-P. Girard, C. Cayrol. (2012) IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G. Proceedings of the National Academy of Sciences
CrossRef12
M. Kabesch. (2012) The role of IgE in difficult-to-treat asthma. Of compliance and competence. Allergy 67:1, 1-2
CrossRef13
E V Bräuner, S Loft, O Raaschou-Nielsen, U Vogel, P S Andersen, M Sørensen. (2012) Effects of a 17q21 chromosome gene variant, tobacco smoke and furred pets on infant wheeze. Genes and Immunity 13:1, 94-97
CrossRef14
Youming Zhang, Miriam F. Moffatt, William O.C. Cookson. (2012) Genetic and genomic approaches to asthma. Current Opinion in Pulmonary Medicine 18:1, 6-13
CrossRef15
S. Wenzel. (2012) Severe asthma: from characteristics to phenotypes to endotypes. Clinical & Experimental Allergyn/a-n/a
CrossRef16
M Janzi, E Melén, I Kull, M Wickman, L Hammarström. (2012) Rare mutations in TNFRSF13B increase the risk of asthma symptoms in Swedish children. Genes and Immunity 13:1, 59-65
CrossRef17
Susanne C. Diesner, Ana Olivera, Sandra Dillahunt, Cornelia Schultz, Thomas Watzlawek, Elisabeth Förster-Waldl, Arnold Pollak, Erika Jensen-Jarolim, Eva Untersmayr, Juan Rivera. (2012) Sphingosine-kinase 1 and 2 contribute to oral sensitization and effector phase in a mouse model of food allergy. Immunology Letters 141:2, 210-219
CrossRef18
Hye Young Kim, Ya-Jen Chang, Srividya Subramanian, Hyun-Hee Lee, Lee A. Albacker, Ponpan Matangkasombut, Paul B. Savage, Andrew N.J. McKenzie, Dirk E. Smith, James B. Rottman, Rosemarie H. DeKruyff, Dale T. Umetsu. (2012) Innate lymphoid cells responding to IL-33 mediate airway hyperreactivity independently of adaptive immunity. Journal of Allergy and Clinical Immunology 129:1, 216-227.e6
CrossRef19
Kian F. Chung. (2012) Inflammatory biomarkers in severe asthma. Current Opinion in Pulmonary Medicine 18:1, 35-41
CrossRef20
Simon Francis Thomsen, Sophie van der Sluis, Kirsten Ohm Kyvik, Vibeke Backer. (2012) A study of asthma severity in adult twins. The Clinical Respiratory Journalno-no
CrossRef21
Laurence Macia, Alison N. Thorburn, Lauren C. Binge, Eliana Marino, Kate E. Rogers, Kendle M. Maslowski, Angélica T. Vieira, Jan Kranich, Charles R. Mackay. (2012) Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases. Immunological Reviews 245:1, 164-176
CrossRef22
Carla P. Jones, Lisa G. Gregory, Benjamin Causton, Gaynor A. Campbell, Clare M. Lloyd. (2012) Activin A and TGF-β promote TH9 cell–mediated pulmonary allergic pathology. Journal of Allergy and Clinical Immunology
CrossRef23
Donata Vercelli. (2012) Remembrance of things past: HLA genes come back on the allergy stage. Journal of Allergy and Clinical Immunology
CrossRef24
Susanne C. Diesner, Elisabeth Förster-Waldl, Ana Olivera, Arnold Pollak, Erika Jensen-Jarolim, Eva Untersmayr. (2012) Perspectives on immunomodulation early in life. Pediatric Allergy and Immunologyno-no
CrossRef25
Simon G. Royce, Victor Cheng, Chrishan S. Samuel, Mimi L.K. Tang. (2012) The regulation of fibrosis in airway remodeling in asthma. Molecular and Cellular Endocrinology
CrossRef26
Lavinia Paternoster, Marie Standl, Chih-Mei Chen, Adaikalavan Ramasamy, Klaus Bønnelykke, Liesbeth Duijts, Manuel A Ferreira, Alexessander Couto Alves, Jacob P Thyssen, Eva Albrecht, Hansjörg Baurecht, Bjarke Feenstra, Patrick M A Sleiman, Pirro Hysi, Nicole M Warrington, Ivan Curjuric, Ronny Myhre, John A Curtin, Maria M Groen-Blokhuis, Marjan Kerkhof, Annika Sääf, Andre Franke, David Ellinghaus, Regina Fölster-Holst, Emmanouil Dermitzakis, Stephen B Montgomery, Holger Prokisch, Katharina Heim, Anna-Liisa Hartikainen, Anneli Pouta, Juha Pekkanen, Alexandra I F Blakemore, Jessica L Buxton, Marika Kaakinen, David L Duffy, Pamela A Madden, Andrew C Heath, Grant W Montgomery, Philip J Thompson, Melanie C Matheson, Peter Le Souëf, Beate St. Pourcain, George Davey Smith, John Henderson, John P Kemp, Nicholas J Timpson, Panos Deloukas, Susan M Ring, H-Erich Wichmann, Martina Müller-Nurasyid, Natalija Novak, Norman Klopp, Elke Rodríguez, Wendy McArdle, Allan Linneberg, Torkil Menné, Ellen A Nohr, Albert Hofman, André G Uitterlinden, Cornélia M van Duijn, Fernando Rivadeneira, Johan C de Jongste, Ralf J P van der Valk, Matthias Wjst, Rain Jogi, Frank Geller, Heather A Boyd, Jeffrey C Murray, Cecilia Kim, Frank Mentch, Michael March, Massimo Mangino, Tim D Spector, Veronique Bataille, Craig E Pennell, Patrick G Holt, Peter Sly, Carla M T Tiesler, Elisabeth Thiering, Thomas Illig, Medea Imboden, Wenche Nystad, Angela Simpson, Jouke-Jan Hottenga, Dirkje Postma, Gerard H Koppelman, Henriette A Smit, Cilla Söderhäll, Bo Chawes, Eskil Kreiner-Møller, Hans Bisgaard, Erik Melén, Dorret I Boomsma, Adnan Custovic, Bo Jacobsson, Nicole M Probst-Hensch, Lyle J Palmer, Daniel Glass, Hakon Hakonarson, Mads Melbye, Deborah L Jarvis, Vincent W V Jaddoe, Christian Gieger, David P Strachan, Nicholas G Martin, Marjo-Riitta Jarvelin, Joachim Heinrich, David M Evans, Stephan Weidinger. (2011) Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nature Genetics
CrossRef27
Jennifer Goldman, Mara L Becker, Bridgette Jones, Mark Clements, J Steven Leeder. (2011) Development of biomarkers to optimize pediatric patient management: what makes children different?. Biomarkers in Medicine 5:6, 781-794
CrossRef28
Harald Renz, Ingo B. Autenrieth, Per Brandtzæg, William O. Cookson, Stephen Holgate, Erika von Mutius, Rudolf Valenta, Dirk Haller. (2011) Gene-environment interaction in chronic disease: A European Science Foundation Forward Look. Journal of Allergy and Clinical Immunology 128:6, S27-S49
CrossRef29
Fredrik Stenius, Magnus Borres, Matteo Bottai, Gunnar Lilja, Frank Lindblad, Göran Pershagen, Annika Scheynius, Jackie Swartz, Töres Theorell, Johan Alm. (2011) Salivary cortisol levels and allergy in children: The ALADDIN birth cohort. Journal of Allergy and Clinical Immunology 128:6, 1335-1339
CrossRef30
C. E. Brightling, S. Gupta, S. Gonem, S. Siddiqui. (2011) Lung damage and airway remodelling in severe asthma. Clinical & Experimental Allergyn/a-n/a
CrossRef31
Shuqiang Qu, Donglin Sun, Yan Wang, Chi Zhang, Ying Lv, Li Yao. (2011) Association of ADAM33 polymorphisms with childhood asthma in a northern Chinese population. Experimental and Molecular Pathology 91:3, 775-779
CrossRef32
C. H. Katelaris, A. Linneberg, A. Magnan, W. R. Thomas, A. J. Wardlaw, P. Wark. (2011) Developments in the field of allergy in 2010 through the eyes of Clinical and Experimental Allergy. Clinical & Experimental Allergy 41:12, 1690-1710
CrossRef33
A. S. Karunas, B. B. Yunusbaev, Yu. Yu. Fedorova, G. F. Gimalova, N. N. Ramazanova, L. L. Gur’eva, L. A. Mukhtarova, Sh. Z. Zagidullin, E. I. Etkina, E. K. Khusnutdinova. (2011) Genome-wide association study of bronchial asthma in the Volga-Urals region of Russia. Molecular Biology 45:6, 911-920
CrossRef34
Mónica Bayés, Ivo Glynne Gut. 2011. Overview of Genotyping. , 1-23.
CrossRef35
Nada M. Saleh, Srilakshmi M. Raj, Deborah J. Smyth, Chris Wallace, Joanna M. M. Howson, Louise Bell, Neil M. Walker, Helen E. Stevens, John A. Todd. (2011) Genetic association analyses of atopic illness and proinflammatory cytokine genes with type 1 diabetes. Diabetes/Metabolism Research and Reviews 27:8, 838-843
CrossRef36
Andrew L. Durham, Coen Wiegman, Ian M. Adcock. (2011) Epigenetics of asthma. Biochimica et Biophysica Acta (BBA) - General Subjects 1810:11, 1103-1109
CrossRef37
Fernando D. Martinez. (2011) New insights into the natural history of asthma: Primary prevention on the horizon. Journal of Allergy and Clinical Immunology 128:5, 939-945
CrossRef38
A. Rogers, S. Bunyavanich. (2011) Unravelling gene-by-environment effects in asthma and allergy: the glutathione pathway as an early success story. Clinical & Experimental Allergy 41:11, 1502-1504
CrossRef39
X. Liu, G. Wang, X. Hong, D. Wang, H.-J. Tsai, S. Zhang, L. Arguelles, R. Kumar, H. Wang, R. Liu, Y. Zhou, C. Pearson, K. Ortiz, R. Schleimer, P. G. Holt, J. Pongracic, H. E. Price, C. Langman, X. Wang. (2011) Gene-vitamin D interactions on food sensitization: a prospective birth cohort study. Allergy 66:11, 1442-1448
CrossRef40
Mark Granada, Jemma B. Wilk, Marina Tuzova, David P. Strachan, Stephan Weidinger, Eva Albrecht, Christian Gieger, Joachim Heinrich, Blanca E. Himes, Gary M. Hunninghake, Juan C. Celedón, Scott T. Weiss, William W. Cruikshank, Lindsay A. Farrer, David M. Center, George T. O'Connor. (2011) A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study. Journal of Allergy and Clinical Immunology
CrossRef41
Adaikalavan Ramasamy, Ivan Curjuric, Lachlan J. Coin, Ashish Kumar, Wendy L. McArdle, Medea Imboden, Benedicte Leynaert, Manolis Kogevinas, Peter Schmid-Grendelmeier, Juha Pekkanen, Matthias Wjst, Andreas J. Bircher, Ulla Sovio, Thierry Rochat, Anna-Liisa Hartikainen, David J. Balding, Marjo-Riitta Jarvelin, Nicole Probst-Hensch, David P. Strachan, Deborah L. Jarvis. (2011) A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. Journal of Allergy and Clinical Immunology 128:5, 996-1005
CrossRef42
María Pino-Yanes, Inmaculada Sánchez-Machín, José Cumplido, Javier Figueroa, María José Torres-Galván, Ruperto González, Almudena Corrales, Orlando Acosta-Fernández, José Carlos García-Robaina, Teresa Carrillo, Anselmo Sánchez-Palacios, Jesús Villar, Mariano Hernández, Carlos Flores. (2011) IL-1 receptor–associated kinase 3 gene (IRAK3) variants associate with asthma in a replication study in the Spanish population. Journal of Allergy and Clinical Immunology
CrossRef43
, David R. Crosslin, Andrew McDavid, Noah Weston, Sarah C. Nelson, Xiuwen Zheng, Eugene Hart, Mariza Andrade, Iftikhar J. Kullo, Catherine A. McCarty, Kimberly F. Doheny, Elizabeth Pugh, Abel Kho, M. Geoffrey Hayes, Stephanie Pretel, Alexander Saip, Marylyn D. Ritchie, Dana C. Crawford, Paul K. Crane, Katherine Newton, Rongling Li, Daniel B. Mirel, Andrew Crenshaw, Eric B. Larson, Chris S. Carlson, Gail P. Jarvik. (2011) Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE Network. Human Genetics
CrossRef44
C. E. Kuehni, C. S. Rueegg, G. Michel, C. E. Rebholz, M.-P. F. Strippoli, F. K. Niggli, M. Egger, N. X. von der Weid, . (2011) Cohort profile: The Swiss Childhood Cancer Survivor Study. International Journal of Epidemiology
CrossRef45
Allan Lawrie, Abdul G. Hameed, Janet Chamberlain, Nadine Arnold, Aneurin Kennerley, Kay Hopkinson, Josephine Pickworth, David G. Kiely, David C. Crossman, Sheila E. Francis. (2011) Paigen Diet–Fed Apolipoprotein E Knockout Mice Develop Severe Pulmonary Hypertension in an Interleukin-1–Dependent Manner. The American Journal of Pathology 179:4, 1693-1705
CrossRef46
Gerard H. Koppelman, Martijn C. Nawijn. (2011) Recent advances in the epigenetics and genomics of asthma. Current Opinion in Allergy and Clinical Immunology 11:5, 414-419
CrossRef47
Barbara Hrdlickova, Lydie Izakovicova Holla. (2011) Relationship between the 17q21 locus and adult asthma in a Czech population. Human Immunology 72:10, 921-925
CrossRef48
Stefano Guerra, Fernando D. Martinez. (2011) Is Allergy an Asthmatic Disease?. Archivos de Bronconeumología (English Edition) 47:10, 479-481
CrossRef49
Stefano Guerra, Fernando D. Martinez. (2011) ¿Es la alergia una enfermedad asmática?. Archivos de Bronconeumología 47:10, 479-481
CrossRef50
F. Stenius, J. Swartz, G. Lilja, M. Borres, M. Bottai, G. Pershagen, A. Scheynius, J. Alm. (2011) Lifestyle factors and sensitization in children - the ALADDIN birth cohort. Allergy 66:10, 1330-1338
CrossRef51
Audrey Poon, Augusto A. Litonjua, Catherine Laprise. (2011) Relevance and implication of genetic determinants to asthma pathophysiology. Current Opinion in Allergy and Clinical Immunology 11:5, 407-413
CrossRef52
Jeroen Douwes, Collin Brooks, Christine Dalen, Neil Pearce. (2011) Importance of Allergy in Asthma: An Epidemiologic Perspective. Current Allergy and Asthma Reports 11:5, 434-444
CrossRef53
Valérie Siroux, Judith Garcia-Aymerich. (2011) The investigation of asthma phenotypes. Current Opinion in Allergy and Clinical Immunology 11:5, 393-399
CrossRef54
Euan R. Tovey, Guy B. Marks. (2011) It’s time to rethink mite allergen avoidance. Journal of Allergy and Clinical Immunology 128:4, 723-727.e6
CrossRef55
Margaret Kurzius-Spencer, Stefano Guerra, Duane L. Sherrill, Marilyn Halonen, Robert C. Elston, Fernando D. Martinez. (2011) Familial aggregation of allergen-specific sensitization and asthma. Pediatric Allergy and Immunologyno-no
CrossRef56
Audrey H. Poon, Fazila Chouiali, Sze Man Tse, Augusto A. Litonjua, Sabah N.A. Hussain, Carolyn J. Baglole, David H. Eidelman, Ronald Olivenstein, James G. Martin, Scott T. Weiss, Qutayba Hamid, Catherine Laprise. (2011) Genetic and histologic evidence for autophagy in asthma pathogenesis. Journal of Allergy and Clinical Immunology
CrossRef57
S. Bunyavanich, J. A. Boyce, B. A. Raby, S. T. Weiss. (2011) Gene-by-environment effect of house dust mite on purinergic receptor P2Y12 (P2RY12) and lung function in children with asthma. Clinical & Experimental Allergyn/a-n/a
CrossRef58
Holger Heine. (2011) TLRs, NLRs and RLRs: Innate sensors and their impact on allergic diseases – A current view. Immunology Letters 139:1-2, 14-24
CrossRef59
Kevin Mullane. (2011) The increasing challenge of discovering asthma drugs. Biochemical Pharmacology 82:6, 586-599
CrossRef60
Francesca Belpinati, Giovanni Malerba, Elisabetta Trabetti, Roberta Galavotti, Luciano Xumerle, Lydia Pescollderungg, Attilio Loris Boner, Pier Franco Pignatti. (2011) Association of childhood allergic asthma with markers flanking the IL33 gene in Italian families. Journal of Allergy and Clinical Immunology 128:3, 667-668
CrossRef61
Manuel AR Ferreira, Melanie C Matheson, David L Duffy, Guy B Marks, Jennie Hui, Peter Le Souëf, Patrick Danoy, Svetlana Baltic, Dale R Nyholt, Mark Jenkins, Catherine Hayden, Gonneke Willemsen, Wei Ang, Mikko Kuokkanen, John Beilby, Faang Cheah, Eco JC de Geus, Adaikalavan Ramasamy, Sailaja Vedantam, Veikko Salomaa, Pamela A Madden, Andrew C Heath, John L Hopper, Peter M Visscher, Bill Musk, Stephen R Leeder, Marjo-Riitta Jarvelin, Craig Pennell, Dorret I Boomsma, Joel N Hirschhorn, Haydn Walters, Nicholas G Martin, Alan James, Graham Jones, Michael J Abramson, Colin F Robertson, Shyamali C Dharmage, Matthew A Brown, Grant W Montgomery, Philip J Thompson. (2011) Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. The Lancet 378:9795, 1006-1014
CrossRef62
Jon Genuneit, Gisela Büchele, Marco Waser, Katalin Kovacs, Anna Debinska, Andrzej Boznanski, Christine Strunz-Lehner, Elisabeth Horak, Paul Cullinan, Dick Heederik, Charlotte Braun-Fahrländer, Erika von Mutius, . (2011) The GABRIEL Advanced Surveys: study design, participation and evaluation of bias. Paediatric and Perinatal Epidemiology 25:5, 436-447
CrossRef63
Hanna Danielewicz, Andrzej Boznański, Anna Dębińska. (2011) Astma i otyłość – czy można mówić o wspólnych uwarunkowaniach genetycznych tych chorób?. Pediatria Polska 86:6, 574-581
CrossRef64
Hans Bisgaard, Nan Li, Klaus Bonnelykke, Bo Lund Krogsgaard Chawes, Thomas Skov, Georg Paludan-Müller, Jakob Stokholm, Birgitte Smith, Karen Angeliki Krogfelt. (2011) Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. Journal of Allergy and Clinical Immunology 128:3, 646-652.e5
CrossRef65
Gerard H. Koppelman, Ian Sayers. (2011) Evidence of a genetic contribution to lung function decline in asthma. Journal of Allergy and Clinical Immunology 128:3, 479-484
CrossRef66
Kathleen C Barnes. (2011) Successfully mapping novel asthma loci by GWAS. The Lancet 378:9795, 967-968
CrossRef67
Gillian M. Bell, Gary Reynolds, John D. Isaacs. (2011) Biologic therapies in non-rheumatic diseases: lessons for rheumatologists?. Nature Reviews Rheumatology 7:9, 507-516
CrossRef68
Carlo Selmi. (2011) Novel Challenges for the Allergist. Clinical Reviews in Allergy & Immunology 41:1, 1-3
CrossRef69
William Cookson, Miriam Moffatt, David P. Strachan. (2011) Genetic risks and childhood-onset asthma. Journal of Allergy and Clinical Immunology 128:2, 266-270
CrossRef70
Anthony M. Holmes, Roberto Solari, Stephen T. Holgate. (2011) Animal models of asthma: value, limitations and opportunities for alternative approaches. Drug Discovery Today 16:15-16, 659-670
CrossRef71
M. Isidoro-García, C. Sanz, V. García-Solaesa, M. Pascual, D. B. Pescador, F. Lorente, I. Dávila. (2011) PTGDR gene in asthma: a functional, genetic, and epigenetic study. Allergyno-no
CrossRef72
Tomomitsu Hirota, Atsushi Takahashi, Michiaki Kubo, Tatsuhiko Tsunoda, Kaori Tomita, Satoru Doi, Kimie Fujita, Akihiko Miyatake, Tadao Enomoto, Takehiko Miyagawa, Mitsuru Adachi, Hiroshi Tanaka, Akio Niimi, Hisako Matsumoto, Isao Ito, Hironori Masuko, Tohru Sakamoto, Nobuyuki Hizawa, Masami Taniguchi, John J Lima, Charles G Irvin, Stephen P Peters, Blanca E Himes, Augusto A Litonjua, Kelan G Tantisira, Scott T Weiss, Naoyuki Kamatani, Yusuke Nakamura, Mayumi Tamari. (2011) Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population. Nature Genetics 43:9, 893-896
CrossRef73
Dara G Torgerson, Elizabeth J Ampleford, Grace Y Chiu, W James Gauderman, Christopher R Gignoux, Penelope E Graves, Blanca E Himes, Albert M Levin, Rasika A Mathias, Dana B Hancock, James W Baurley, Celeste Eng, Debra A Stern, Juan C Celedón, Nicholas Rafaels, Daniel Capurso, David V Conti, Lindsey A Roth, Manuel Soto-Quiros, Alkis Togias, Xingnan Li, Rachel A Myers, Isabelle Romieu, David J Van Den Berg, Donglei Hu, Nadia N Hansel, Ryan D Hernandez, Elliott Israel, Muhammad T Salam, Joshua Galanter, Pedro C Avila, Lydiana Avila, Jose R Rodriquez-Santana, Rocio Chapela, William Rodriguez-Cintron, Gregory B Diette, N Franklin Adkinson, Rebekah A Abel, Kevin D Ross, Min Shi, Mezbah U Faruque, Georgia M Dunston, Harold R Watson, Vito J Mantese, Serpil C Ezurum, Liming Liang, Ingo Ruczinski, Jean G Ford, Scott Huntsman, Kian Fan Chung, Hita Vora, Xia Li, William J Calhoun, Mario Castro, Juan J Sienra-Monge, Blanca del Rio-Navarro, Klaus A Deichmann, Andrea Heinzmann, Sally E Wenzel, William W Busse, James E Gern, Robert F Lemanske, Terri H Beaty, Eugene R Bleecker, Benjamin A Raby, Deborah A Meyers, Stephanie J London, Frank D Gilliland, Esteban G Burchard, Fernando D Martinez, Scott T Weiss, L Keoki Williams, Kathleen C Barnes, Carole Ober, Dan L Nicolae. (2011) Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nature Genetics 43:9, 887-892
CrossRef74
Joshua M. Galanter, Dara Torgerson, Christopher R. Gignoux, Saunak Sen, Lindsey A. Roth, Marc Via, Melinda C. Aldrich, Celeste Eng, Scott Huntsman, Jose Rodriguez-Santana, William Rodriguez-Cintrón, Rocio Chapela, Jean G. Ford, Esteban G. Burchard. (2011) Cosmopolitan and ethnic-specific replication of genetic risk factors for asthma in 2 Latino populations. Journal of Allergy and Clinical Immunology 128:1, 37-43.e12
CrossRef75
Carole Ober, Tsung-Chieh Yao. (2011) The genetics of asthma and allergic disease: a 21st century perspective. Immunological Reviews 242:1, 10-30
CrossRef76
Anna Lluis, Michaela Schedel, Jing Liu, Sabina Illi, Martin Depner, Erika von Mutius, Michael Kabesch, Bianca Schaub. (2011) Asthma-associated polymorphisms in 17q21 influence cord blood ORMDL3 and GSDMA gene expression and IL-17 secretion. Journal of Allergy and Clinical Immunology 127:6, 1587-1594.e6
CrossRef77
Francine Kauffmann, Raphaëlle Varraso. (2011) The epidemiology of cough. Pulmonary Pharmacology & Therapeutics 24:3, 289-294
CrossRef78
Thomas Eiwegger, Cezmi A. Akdis. (2011) IL-33 links tissue cells, dendritic cells and Th2 cell development in a mouse model of asthma. European Journal of Immunology 41:6, 1535-1538
CrossRef79
John Trowsdale. (2011) The MHC, disease and selection. Immunology Letters 137:1-2, 1-8
CrossRef80
Ya-Jen Chang, Hye Young Kim, Lee A Albacker, Nicole Baumgarth, Andrew N J McKenzie, Dirk E Smith, Rosemarie H DeKruyff, Dale T Umetsu. (2011) Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity. Nature Immunology 12:7, 631-638
CrossRef81
Ma'en Obeidat, Ian P. Hall. (2011) Genetics of complex respiratory diseases: implications for pathophysiology and pharmacology studies. British Journal of Pharmacology 163:1, 96-105
CrossRef82
Arthur Kaser, Richard S. Blumberg. (2011) Autophagy, Microbial Sensing, Endoplasmic Reticulum Stress, and Epithelial Function in Inflammatory Bowel Disease. Gastroenterology 140:6, 1738-1747.e2
CrossRef83
Judy H. Cho, Steven R. Brant. (2011) Recent Insights Into the Genetics of Inflammatory Bowel Disease. Gastroenterology 140:6, 1704-1712.e2
CrossRef84
HELEN K. REDDEL, T. K. LIM, MICHIAKI MISHIMA, CLAIRE E. WAINWRIGHT, DARRYL A. KNIGHT. (2011) Year-in-review 2010: Asthma, COPD, cystic fibrosis and airway biology. Respirology 16:3, 540-552
CrossRef85
LOUBNA AKHABIR, ANDREW J. SANDFORD. (2011) Genome-wide association studies for discovery of genes involved in asthma. Respirology 16:3, 396-406
CrossRef86
Carole Ober, Donata Vercelli. (2011) Gene–environment interactions in human disease: nuisance or opportunity?. Trends in Genetics 27:3, 107-115
CrossRef87
Ege, Markus J., Mayer, Melanie, Normand, Anne-Cécile, Genuneit, Jon, Cookson, William O.C.M., Braun-Fahrländer, Charlotte, Heederik, Dick, Piarroux, Renaud, von Mutius, Erika, . (2011) Exposure to Environmental Microorganisms and Childhood Asthma. New England Journal of Medicine 364:8, 701-709
Full Text88
Riccardina Tesse, Maximilian Schieck, Michael Kabesch. (2011) Asthma and endocrine disorders: Shared mechanisms and genetic pleiotropy. Molecular and Cellular Endocrinology 333:2, 103-111
CrossRef89
Hancock, Dana B., London, Stephanie J., . (2011) Determinants of Lung Function, COPD, and Asthma. New England Journal of Medicine 364:1, 86-87
Full Text90
Ernesto Prado Montes de Oca. (2011) Human Polymorphisms as Clinical Predictors in Leprosy. Journal of Tropical Medicine 2011, 1-14
CrossRef91
Keisuke Oboki, Susumu Nakae, Kenji Matsumoto, Hirohisa Saito. (2011) IL-33 and Airway Inflammation. Allergy, Asthma and Immunology Research 3:2, 81
CrossRef92
Erik Melén, Alvin T Kho, Sunita Sharma, Roger Gaedigk, J Steven Leeder, Thomas J Mariani, Vincent J Carey, Scott T Weiss, Kelan G Tantisira. (2011) Expression analysis of asthma candidate genes during human and murine lung development. Respiratory Research 12:1, 86
CrossRef93
Mayumi Tamari, Kaori Tomita, Tomomitsu Hirota. (2011) Genome-Wide Association Studies of Asthma. Allergology International 60:3, 247-252
CrossRef94
Shin-Hwa Lee, Jong-Sook Park, Choon-Sik Park. (2011) The Search for Genetic Variants and Epigenetics Related to Asthma. Allergy, Asthma and Immunology Research 3:4, 236
CrossRef95
Yonggang Zhang, Can Tian, Jie Zhang, Xiaobo Li, Hua Wan, Chao He, Liang Guo, Quocuo Meilang, Chunhong Peng, Lina Duo, Jin Huang, Hong Fan. (2011) The −159C/T polymorphism in the CD14 gene and the risk of asthma: a meta-analysis. Immunogenetics 63:1, 23-32
CrossRef96
MAYUMI TAMARI. (2011) Nippon Jibiinkoka Gakkai Kaiho 114:5, 477-484
CrossRef97
Ramani Anantharaman, Anand Kumar Andiappan, Pallavi Parate Nilkanth, Bani Kaur Suri, De Yun Wang, Fook Tim Chew. (2011) Genome-wide association study identifies PERLD1 as asthma candidate gene. BMC Medical Genetics 12:1, 170
CrossRef98
Clare M. Lloyd. (2010) IL-33 family members and asthma – bridging innate and adaptive immune responses. Current Opinion in Immunology 22:6, 800-806
CrossRef99
F. Boralevi. (2010) Quoi de neuf en dermatologie pédiatrique en 2010 ?. Annales de Dermatologie et de Vénéréologie 137, S145-S157
CrossRef100
(2010) Research highlights. Nature Genetics 42:11, 929-929
CrossRef
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