| 1. |
- Artigas Soler, María, et al.
(författare)
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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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| 2. |
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| 3. |
- Castro-Giner, F, et al.
(författare)
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TNFA -308G>A in two international population-based cohorts and risk of asthma
- 2008
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Ingår i: European Respiratory Journal. - Sheffield : European respiratory society journals. - 0903-1936 .- 1399-3003. ; 32:2, s. 350-361
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Tidskriftsartikel (refereegranskat)abstract
- Genetic association studies have related the tumour necrosis factor-alpha gene (TNFA) guanine to adenine substitution of nucleotide -308 (-308G>A) polymorphism to increased risk of asthma, but results are inconsistent. The aim of the present study was to test whether two single-nucleotide polymorphisms, of TNFA and of the lymphotoxin-alpha gene (LTA), are associated with asthma, bronchial hyperresponsiveness and atopy in adults, by combining the results of two large population-based multicentric studies and conducting a meta-analysis of previously published studies. The European Community Respiratory Health Survey (ECRHS) and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) used comparable protocols, including questionnaires for respiratory symptoms and measures of lung function and atopy. DNA samples from 11,136 participants were genotyped at TNFA -308 and LTA 252. Logistic regression employing fixed and random effects models and nonparametric techniques were used. The prevalence of asthma was 6%. The TNFA -308G>A polymorphism was associated with increased asthma prevalence and with bronchial hyperresponsiveness. No consistent association was found for atopy. The LTA 252A>G polymorphism was not associated with any of the outcomes. A meta-analysis of 17 studies showed an increased asthma risk for the TNFA -308 adenine allele. The tumour necrosis factor-alpha gene nucleotide -308 polymorphism is associated with a moderately increased risk of asthma and bronchial hyperresponsiveness, but not with atopy. These results are supported by a meta-analysis of previously published studies.
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| 4. |
- Loth, Daan W, et al.
(författare)
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Genome-wide association analysis identifies six new loci associated with forced vital capacity
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
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Tidskriftsartikel (refereegranskat)abstract
- Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
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| 5. |
- Canova, C., et al.
(författare)
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The influence of sensitisation to pollens and moulds on seasonal variations in asthma attacks
- 2013
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 42:4, s. 935-945
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Tidskriftsartikel (refereegranskat)abstract
- No large study has described the seasonal variation in asthma attacks in population-based asthmatics in whom sensitisation to allergen has been measured. 2637 young adults with asthma living in 15 countries reported the months in which they usually had attacks of asthma and had skin-prick tests performed. Differences in seasonal patterns by sensitisation status were assessed using generalised estimating equations. Most young adults with asthma reported periods of the year when their asthma attacks were more common (range: 47% in Sweden to 86% in Spain). Seasonal variation in asthma was not modified by sensitisation to house dust mite or cat allergens. Asthmatics sensitised to grass, birch and Alternaria allergens had different seasonal patterns to those not sensitised to each allergen, with some geographical variation. In southern Europe, those sensitised to grass allergens were more likely to report attacks occurred in spring or summer than in winter (OR March/April 2.60, 95% CI 1.70-3.97; OR May/June 4.43, 95% CI 2.34-8.39) and smaller later peaks were observed in northern Europe (OR May/June 1.25, 95% CI 0.60-2.64; OR July/August 1.66, 95% CI 0.89-3.10). Asthmatics reporting hay fever but who were not sensitised to grass showed no seasonal variations. Seasonal variations in asthma attacks in young adults are common and are different depending on sensitisation to outdoor, but not indoor, allergens.
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| 6. |
- Campbell, B, et al.
(författare)
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The effects of growing up on a farm on adult lung function and allergic phenotypes : an international population-based study
- 2017
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 72:3, s. 236-244
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Evidence has suggested that exposure to environmental or microbial biodiversity in early life may impact subsequent lung function and allergic disease risk.OBJECTIVES: To investigate the influence of childhood living environment and biodiversity indicators on atopy, asthma and lung function in adulthood.METHODS AND MEASUREMENTS: The European Community Respiratory Health Survey II investigated ∼10 201 participants aged 26-54 years from 14 countries, including participants' place of upbringing (farm, rural environment or inner city) before age 5 years. A 'biodiversity score' was created based on childhood exposure to cats, dogs, day care, bedroom sharing and older siblings. Associations with lung function, bronchial hyper-responsiveness (BHR), allergic sensitisation, asthma and rhinitis were analysed.MAIN RESULTS: As compared with a city upbringing, those with early-life farm exposure had less atopic sensitisation (adjusted OR 0.46, 95% CI 0.37 to 0.58), atopic BHR (0.54 (0.35 to 0.83)), atopic asthma (0.47 (0.28 to 0.81)) and atopic rhinitis (0.43 (0.32 to 0.57)), but not non-atopic outcomes. Less pronounced protective effects were observed for rural environment exposures. Women with a farm upbringing had higher FEV1 (adjusted difference 110 mL (64 to 157)), independent of sensitisation and asthma. In an inner city environment, a higher biodiversity score was related to less allergic sensitisation.CONCLUSIONS: This is the first study to report beneficial effects of growing up on a farm on adult FEV1. Our study confirmed the beneficial effects of early farm life on sensitisation, asthma and rhinitis, and found a similar association for BHR. In persons with an urban upbringing, a higher biodiversity score predicted less allergic sensitisation, but to a lesser magnitude than a childhood farm environment.
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| 7. |
- Amaral, A F S, et al.
(författare)
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The locus C11orf30 increases susceptibility to poly-sensitization
- 2015
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 70:3, s. 328-333
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Tidskriftsartikel (refereegranskat)abstract
- A number of genetic variants have been associated with allergic sensitization, but whether these are allergen specific or increase susceptibility to poly-sensitization is unknown. Using data from the large multicentre population-based European Community Respiratory Health Survey, we assessed the association between 10 loci and specific IgE and skin prick tests to individual allergens and poly-sensitization. We found that the 10 loci associate with sensitization to different allergens in a nonspecific manner and that one in particular, C11orf30-rs2155219, doubles the risk of poly-sensitization (specific IgE/4 allergens: OR = 1.81, 95% CI 0.80-4.24; skin prick test/4+ allergens: OR = 2.27, 95% CI 1.34-3.95). The association of rs2155219 with higher levels of expression of C11orf30, which may be involved in transcription repression of interferon-stimulated genes, and its association with sensitization to multiple allergens suggest that this locus is highly relevant for atopy.
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| 8. |
- de Marco, Roberto, et al.
(författare)
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Asthma, COPD and overlap syndrome : a longitudinal study in young European adults
- 2015
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 46:3, s. 671-679
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Tidskriftsartikel (refereegranskat)abstract
- We compared risk factors and clinical characteristics, 9-year lung function change and hospitalisation risk across subjects with the asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), asthma or COPD alone, or none of these diseases. Participants in the European Community Respiratory Health Survey in 1991-1993 (aged 20-44 years) and 1999-2001 were included. Chronic airflow obstruction was defined as pre-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity
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| 9. |
- Leynaert, Benedicte, et al.
(författare)
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Gender differences in prevalence, diagnosis and incidence of allergic and non-allergic asthma : a population-based cohort
- 2012
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 67:7, s. 625-631
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Tidskriftsartikel (refereegranskat)abstract
- Background Although women with severe non-allergic asthma may represent a substantial proportion of adults with asthma in clinical practice, gender differences in the incidence of allergic and non-allergic asthma have been little investigated in the general population. Methods Gender differences in asthma prevalence, reported diagnosis and incidence were investigated in 9091 men and women randomly selected from the general population and followed up after 8-10 years as part of the European Community Respiratory Health Survey. The protocol included assessment of bronchial responsiveness, IgE specific to four common allergens and skin tests to nine allergens. Results Asthma was 20% more frequent in women than in men over the age of 35 years. Possible under-diagnosis of asthma appeared to be particularly frequent among non-atopic individuals, but was as frequent in women as in men. The follow-up of subjects without asthma at baseline showed a higher incidence of asthma in women than in men (HR 1.94; 95% CI 1.40 to 2.68), which was not explained by differences in smoking, obesity or lung function. More than 60% of women and 30% of men with new-onset asthma were non-atopic. The incidence of non-allergic asthma was higher in women than in men throughout all the reproductive years (HR 3.51; 95% CI 2.21 to 5.58), whereas no gender difference was observed for the incidence of allergic asthma. Conclusions This study shows that female sex is an independent risk factor for non-allergic asthma, and stresses the need for more careful assessment of possible non-allergic asthma in clinical practice, in men and women.
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| 10. |
- Marcon, A., et al.
(författare)
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Can an airway challenge test predict respiratory diseases? A population-based international study
- 2014
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 133:1, s. 104-110.e3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence on the longitudinal association of airway responsiveness with respiratory diseases is scarce. The best indicator of responsiveness is still undetermined. Objective: We investigated the association of airway responsiveness with the incidence of asthma, chronic obstructive pulmonary disease (COPD), and allergic rhinitis. Methods: We studied 3851 subjects who underwent spirometry and methacholine challenge tests both at baseline (1991-1993), when they were 20 to 44 years old, and at follow-up (1999-2002) in the European Community Respiratory Health Survey. Airway responsiveness was defined based on the methacholine dose-response slope on both occasions. Incidence rate ratios for the association of airway responsiveness with disease occurrence were computed by using Poisson regression. Results: With respect to reference (slope of the fourth quintile or greater), subjects with the greatest degree of airway responsiveness (slope less than the first quintile) showed the greatest risk of developing asthma, COPD, and allergic rhinitis (incidence rate ratios of 10.82, 5.53, and 4.84, respectively; all P <.01). A low slope predicted disease occurrence, even in subjects who did not reach a 20% decrease in FEV1 at the cumulative dose of 1 mg of methacholine (PD20 >1 mg). A decrease in slope over time was an independent predictor of disease risk. Conclusion: Airway responsiveness predicted new-onset asthma, COPD, and allergic rhinitis. Our study supports the use of a continuous noncensored indicator of airway responsiveness, such as the slope of the methacholine dose-response curve, in clinical practice and research because it showed clear advantages over PD20. © 2013 American Academy of Allergy, Asthma & Immunology.
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