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- 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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| 3. |
- Sunyer, J., et al.
(författare)
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Asthma score : predictive ability and risk factors
- 2007
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 62:2, s. 142-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: Definition of asthma as a continuous score is a promising tool for population studies that has not yet been fully evaluated. Objective: We assessed (i) the predictive ability of an asthma score against the occurrence of different asthma-related outcomes and (ii) the risk factors identified when using an asthma score. Methods: The European Community Respiratory Health Study II included subjects from the general population randomly studied during 1991-1993 who were followed up in the years 1998-2001, from 29 centres in 14 countries. A total of 8956 subjects were included. The asthma score consisted of a simple sum of the positive answers to five respiratory symptoms. Results: Asthma score at baseline showed a linear relationship with incidence of asthma, the occurrence of asthma attacks, use of asthma medication and bronchial reactivity at the end of the follow-up. Asthma score at the end of follow-up was associated with known risk factors at baseline such as IgE to grass, rhinitis or body mass index, in addition to passive smoking in men [average score ratio (RR) = 1.30; 95% confidence interval (CI) 1.09-1.50] or changes in body mass index (RR = 1.27; 95% CI 1.05-1.27, per each kg/m2). Conclusion: The asthma score had good predictive ability against outcomes related with asthma and also good ability to detect risk factors. This encourages the use of the score as a measure of asthma in epidemiological studies on aetiology of asthma.
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| 4. |
- Ramasamy, Adaikalavan, et al.
(författare)
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Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9, s. e44008-
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies. Objectives: To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations. Methods: The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P < 5x10(-8)) and three variants reported as suggestive (P < 5 x 10(-7)). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever. Main Results: We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4x10(-9)). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (PStage1+Stage2 = 1.1x10(-9)), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (PStage1+Stage2 = 1.1x10(-8)), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status. Conclusions: Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma.
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