Publications
396 results found
Cookson W, Liang L, Abecasis G, et al., 2009, Mapping complex disease traits with global gene expression, NATURE REVIEWS GENETICS, Vol: 10, Pages: 184-194, ISSN: 1471-0056
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- Citations: 590
Willis-Owen SA, Moffatt MF, Cookson WO, 2009, The genetics of asthma and atopic dermatitis., Allergy and Allergic Diseases., Oxford, Publisher: Blackwell Publishing
Willis-Owen SAG, Cookson WOC, 2008, The genetic origins of bronchial asthma, Biologist, Vol: 55, Pages: 224-227, ISSN: 0006-3347
Asthma is a complex disease of multifactorial aetiology, subject to a wide range of genetic and environmental influences, and interactions between these factors. As we enter the post-genome era, advances in technology and knowledge support systems mean that the genetic basis of complex traits can be successfully investigated.
Weinmayr G, Forastiere F, Weiland SK, et al., 2008, International variation in prevalence of rhinitis and its relationship with sensitisation to perennial and seasonal allergens, EUROPEAN RESPIRATORY JOURNAL, Vol: 32, Pages: 1250-1261, ISSN: 0903-1936
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- Citations: 62
Weidinger S, Gieger C, Rodriguez E, et al., 2008, Genome-Wide Scan on Total Serum IgE Levels Identifies <i>FCER1A</i> as Novel Susceptibility Locus, PLOS GENETICS, Vol: 4, ISSN: 1553-7404
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- Citations: 215
Moffatt MF, Cookson WOCM, 2008, Asthma and chitinases, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 358, Pages: 1725-1726, ISSN: 0028-4793
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- Citations: 3
Williams H, Stewart A, von Mutius E, et al., 2008, Is eczema really on the increase worldwide?, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 121, Pages: 947-954, ISSN: 0091-6749
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- Citations: 386
Björkstén B, Clayton T, Ellwood P, et al., 2008, Worldwide time trends for symptoms of rhinitis and conjunctivitis: Phase III of the International Study of Asthma and Allergies in Childhood., Pediatr Allergy Immunol, Vol: 19, Pages: 110-124
In Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC) time trends in the prevalence of rhinoconjunctivitis symptoms were analysed. Cross-sectional questionnaire surveys with identical protocols and questionnaires were completed a mean of 7 yr apart in two age groups comprising 498,083 children. In the 13- to 14-yr age group 106 centres in 56 countries participated, and in the 6- to 7-yr age group 66 centres in 37 countries participated. A slight worldwide increase in rhinoconjunctivitis prevalence was observed, but the variations were large among the centres and there was no consistent regional pattern. Prevalence increases in the older children exceeding 1% per year were recorded in 13 centres, including 3 of 9 centres in Africa, 2 of 15 in Asia-Pacific, 1 of 8 in India, 3 of 15 in Latin America, 3 of 9 in Eastern Europe and 1 of 34 in Western and Northern Europe. Decreasing rhinoconjunctivititis prevalence of similar magnitude was only seen in four centres. The changes were less pronounced in the 6- to 7-yr-old children and only in one centre did any change exceed 1% per year. The decrease in highest prevalence rates in ISAAC Phase I suggests that the prevalence has peaked in those regions. An increase was recorded in several centres, mostly in low and mid-income countries. The increases were more pronounced in the older age group, suggesting that environmental influences on the development of allergy may not be limited to early childhood.
Kleiner A, Flohr C, Weiland S, et al., 2008, International variation in prevalence of flexural eczema and atopic sensitization. Results from phase two of the International Study of Asthma and Allergies in Childhood (ISAAC Phase Two), Allergo Journal, Vol: 17, Pages: 79-81, ISSN: 0941-8849
Background: There is debate in the dermatology literature whether flexural eczema in childhood is really an atopic disease. After a systematic literature review, Flohr et al. concluded that the prevalence of atopy among subjects with flexural eczema varies greatly between study populations and is on average higher in hospital than in community settings. The association between flexural eczema in childhood and atopy in a wide range of study centers was investigated in phase two of the ISAAC study. Detailed results have already been published in the Journal of Allergy and Clinical Immunology. Methods: ISAAC Phase Two is a multicenter cross-sectional study, and 27 centers from 18 countries worldwide contributed data to the presented analysis. The prevalence of symptoms of flexural eczema was determined by parental questionnaire in eight-to twelve-year-old children (approximately 1,000 per center). In addition, a skin examination for flexural eczema was carried out in 30,031 children and a skin prick test for atopy was performed, using six common allergens: Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat, Alternaria tenuis, tree and grass pollen. Some centers tested additional allergens of local relevance. A skin prick test was rated as positive, if the reaction minus the negative control was ≥ 3 mm, and a child was defined as atopic, if it had at least one positive skin prick test. Results: The prevalence of flexural eczema from skin examination shows a high variability and ranges from 0.4% in Kintampo, Ghana, to 14.2% in Östersund, Sweden. The prevalence of atopic flexural eczema (flexural eczema in combination with a positive skin prick test) varies from 0% in Kintampo, Ghana, and Ramallah, West Bank, to 7.0% in Östersund, Sweden. Nonatopic flexural eczema was most common (6.9%) in Östersund, Sweden, and least common (0.4%) in Kintampo, Ghana, and Cartagena, Spain. The proportion of atopic children among children with eczema varies lar
Flohr C, Weiland SK, Weinmayr G, et al., 2008, The role of atopic sensitization in flexural eczema:: Findings from the International Study of Asthma and Allergies in Childhood Phase Two, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 121, Pages: 141-147, ISSN: 0091-6749
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- Citations: 84
Dixon AL, Liang L, Moffatt MF, et al., 2007, A genome-wide association study of global gene expression, NATURE GENETICS, Vol: 39, Pages: 1202-1207, ISSN: 1061-4036
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- Citations: 779
Weinmayr G, Weiland SK, Bjorksten B, et al., 2007, Atopic sensitization and the international variation of asthma symptom prevalence in children, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 176, Pages: 565-574, ISSN: 1073-449X
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- Citations: 240
Pearce N, Aït-Khaled N, Beasley R, et al., 2007, Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC)., Thorax, Vol: 62, Pages: 758-766, ISSN: 0040-6376
BACKGROUND: Phase I of the International Study of Asthma and Allergies in Childhood (ISAAC) was designed to allow worldwide comparisons of the prevalence of asthma symptoms. In phase III the phase I survey was repeated in order to assess changes over time. METHODS: The phase I survey was repeated after an interval of 5-10 years in 106 centres in 56 countries in children aged 13-14 years (n = 304,679) and in 66 centres in 37 countries in children aged 6-7 years (n = 193,404). RESULTS: The mean symptom prevalence of current wheeze in the last 12 months changed slightly from 13.2% to 13.7% in the 13-14 year age group (mean increase of 0.06% per year) and from 11.1% to 11.6% in the 6-7 year age group (mean increase of 0.13% per year). There was also little change in the mean symptom prevalence of severe asthma or the symptom prevalence measured with the asthma video questionnaire. However, the time trends in asthma symptom prevalence showed different regional patterns. In Western Europe, current wheeze decreased by 0.07% per year in children aged 13-14 years but increased by 0.20% per year in children aged 6-7 years. The corresponding findings per year for the other regions in children aged 13-14 years and 6-7 years, respectively, were: Oceania (-0.39% and -0.21%); Latin America (+0.32% and +0.07%); Northern and Eastern Europe (+0.26% and +0.05%); Africa (+0.16% and +0.10%); North America (+0.12% and +0.32%); Eastern Mediterranean (-0.10% and +0.79%); Asia-Pacific (+0.07% and -0.06%); and the Indian subcontinent (+0.02% and +0.06%). There was a particularly marked reduction in current asthma symptom prevalence in English language countries (-0.51% and -0.09%). Similar patterns were observed for symptoms of severe asthma. However, the percentage of children reported to have had asthma at some time in their lives increased by 0.28% per year in the 13-14 year age group and by 0.18% per year in the 6-7 year age group. CONCLUSIONS: These findings indicate that international
Moffatt MF, Kabesch M, Liang L, et al., 2007, Genetic variants regulating <i>ORMDL3</i> expression contribute to the risk of childhood asthma, NATURE, Vol: 448, Pages: 470-U5, ISSN: 0028-0836
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- Citations: 1194
Morar N, Cookson WOCM, Harper JI, et al., 2007, Filaggrin mutations in children with severe atopic dermatitis, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 127, Pages: 1667-1672, ISSN: 0022-202X
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- Citations: 153
Williams HC, Stewart A, von Mutius E, et al., 2007, International study of asthma and allergies in childhood (ISAAC) phase 1 and 3 study groups, Annual Meeting of the British-Society-for-Investigative-Dermatology, Publisher: BLACKWELL PUBLISHING, Pages: 1109-1109, ISSN: 0007-0963
Valdar W, Solberg LC, Gauguier D, et al., 2006, Genetic and Environmental Effects on Complex Traits in Mice, GENETICS, Vol: 174, Pages: 959-984, ISSN: 0016-6731
Cookson WOC, 2006, State of the art. Genetics and genomics of chronic obstructive pulmonary disease., Proc Am Thorac Soc, Vol: 3, Pages: 473-475, ISSN: 1546-3222
Valdar W, Solberg LC, Gauguier D, et al., 2006, Genome-wide genetic association of complex traits in heterogeneous stock mice., Nat Genet, Vol: 38, Pages: 879-887, ISSN: 1061-4036
Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits.
Morar N, Willis-Owen SAG, Moffatt MF, et al., 2006, The genetics of atopic dermatitis, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 118, Pages: 24-34, ISSN: 0091-6749
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- Citations: 185
Weinmayr G, Rzehak P, Büchele G, et al., 2006, International variation in prevalence of asthma symptoms and atopic sensitization: Results from phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II), Allergo Journal, Vol: 15, Pages: 124-125, ISSN: 0941-8849
Background: Atopy is generally considered to be an important risk factor for asthma. However, a literature analysis by Pearce et al. suggests that the role of atopy might have been overestimated in the past. The role of atopy in a wide range of study centers participating in ISAAC II was investigated. Methods: ISAAC II is a multicenter cross-sectional study investigating random samples of approximately 1,000 children per study center aged nine to eleven years according to the same standardized protocol. 29 study centers in 20 countries participated. Parents answered a detailed questionnaire on respiratory and atopic symptoms. In addition, skin prick tests were performed using six common inhalant allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat, Alternaria tenuis, mixed tree pollen, mixed grass pollen). A skin prick test was defined positive, if the reaction to at least one allergen was ≥ 3 mm. Results: There was a large variation in the prevalence of wheeze in the past year ranging from < 1% in rural Ecuador and 3.3% in China to 22.2% in New Zealand and 26.3% in Brasil (Fig. 1). The prevalence of atopic wheeze, defined as wheeze plus a positive skin prick test, varied also largely between 0.1% in Ecuador and 13.4% in New Zealand, as did the prevalence of nonatopic wheeze from 0.5% in China to 20.9% in Brasil. The proportion of atopics varied strongly between centers and tended to be lower in low-income countries. Conclusion: The observed international pattern of asthma prevalence rates confirms findings of ISAAC phase I. Prevalence rates of wheeze were generally higher in high-income countries where they also tended to be more closely related to atopy. Further analyses of this relation are currently ongoing.
Morar N, Bowcock AM, Harper JI, et al., 2006, Investigation of the chromosome 17q25 <i>PSORS2</i> locus in atopic dermatitis, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 126, Pages: 603-606, ISSN: 0022-202X
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- Citations: 16
Solberg LC, Valdar W, Gauguier D, et al., 2006, A Protocol for high throughput phenotyping, suitable for quantitative traits analysis in mice. Mammalian Genome 17: 129-146., Mammalian Genome, ISSN: 0938-8990
Solberg LC, Valdar W, Gauguier D, et al., 2006, A protocol for high-throughput phenotyping, suitable for quantitative trait analysis in mice, MAMMALIAN GENOME, Vol: 17, Pages: 129-146, ISSN: 0938-8990
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- Citations: 85
Moffatt MF, Cookson WOC, 2006, Fine mapping and whole genome association studies in Asthma and chronic obstructive pulmonary disease, Genetics of Asthma and Chronic Obstructive Pulmonary Disease, Pages: 223-238, ISBN: 9780849369667
Positional cloning is much more likely to identify novel genetic effects than candidate gene studies. Genetic linkage studies are very powerful for the study of single gene disorders, but have limited power in complex genetic disorders when many genes are likely to be acting and there is no established model for the inheritance of a given disease. Genetic linkage studies in a complex disorder such as Asthma typically give an imprecise signal for the localization of the diseased gene that may extend over tens of megabases of DNA. This is because only a proportion of families will actually be linked to the locus, while others will appear randomly linked and nonlinked. In addition, the proportion of individuals with susceptibility alleles who develop the disease will vary between families (i.e., the alleles will have variable penetrance). For this reason, even highly ambitious genetic linkage studies involving several hundreds of families have often failed to deliver conclusive results.
Goldstein DB, Foote SJ, Hafler DA, et al., 2005, Discussion, Pages: 39-45, ISSN: 1528-2511
Abbas AK, Wijmenga C, Rioux JD, et al., 2005, Discussion, Pages: 134-144, ISSN: 1528-2511
Daly MJ, Goldstein DB, Rioux JD, et al., 2005, Discussion, Pages: 19-30, ISSN: 1528-2511
Hafler DA, Rao A, Goodnow CC, et al., 2005, Discussion, Pages: 192-199, ISSN: 1528-2511
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