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- 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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- 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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- Macsali, F., et al.
(författare)
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Menstrual Cycle and Respiratory Symptoms in a General Nordic-Baltic Population
- 2013
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 187:4, s. 366-373
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Tidskriftsartikel (refereegranskat)abstract
- Rationale :Thereislittleknowledgeofvariationsinrespiratorysymp- tomsduringthemenstrualcycleinageneralpopulation,andpoten- tial modifying factors are not investigated. Objectives : To investigate menstrual cycle variation in respiratory symptomsinalargegeneralpopulation,usingchronobiologymeth- odology, and stratifying by body mass index (BMI), smoking, and asthma status. Methods : A total of 3,926 women with regular cycles less than or equal to 28 days and not taking exogenous sex hormones answered a postalquestionnaire regarding the first day of their last menstrua- tion and respiratory symptoms in the last 3 days. Moving 4-day meanswerecomputedto smoothunevenrecordsof dailysampling; best-fitting 28-day composite cosine curves were applied to each time series to describe rhythmicity. Measurements and Main Results : Significant rhythmic variations over themenstrualcyclewerefoundineachsymptomforallsubjectsand subgroups. Wheezing was higher on cycle Days 10–22, with a mid- cycle dip near the time of putative ovulation (approximately Days 14–16) in most subgroups. Shortness of breath was higher on days 7–21,withadipjustbeforemidcycleinmanysubgroups.Coughwas higher just after putative ovulation for subjects with asthma, BMI greater than or equal to 23 kg/m 2 , and smokers, or just before ovu- lation and menses onset for low symptomatic subgroups. Conclusions : Respiratory symptoms varied significantly during the menstrual cycle and were most frequent from the midluteal to mid- follicular stages, often with a dip near the time of ovulation. The patternsvariedbyBMI,smoking,andasthmastatus.Theserelations linkrespiratorysymptomswithhormonalchangesthroughthemen- strual cycle and imply a potential for individualized chronotherapy for respiratory diseases.
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- Castro-Giner, F., et al.
(författare)
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Positionally cloned genes and age-specific effects in asthma and atopy : an international population-based cohort study (ECRHS)
- 2010
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 65:2, s. 124-131
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Tidskriftsartikel (refereegranskat)abstract
- Background Several genes identified by positional cloning have been associated with asthma and atopy, but few findings have been replicated. Age at onset of asthma has been associated with different phenotypic characteristics, and with variants at chromosome 17q21 identified through genome-wide association. This study examined the associations and age-specific effects on asthma, atopy and bronchial hyper-responsiveness (BHR) of five candidate genes previously identified by positional cloning (ADAM33, PHF11, NPSR1, DPP10, SPINK5). Methods 51 polymorphisms from 2474 participants from 13 countries who took part in the European Community Respiratory Health Survey (1990-2000) were studied. Asthma and age at onset of asthma were assessed by questionnaire data, BHR by methacholine challenge and atopy by specific immunoglobulin E to four common allergens. Results Significant associations with asthma, atopy and particularly for asthma with atopy were observed for a large region of 47 kb in the NPSR1 gene, even after Bonferroni correction for multiple comparisons (p < 0.001). The associations with NPSR1 were stronger in those reporting a first attack of asthma before the age of 15, with statistically significant interactions with age of onset found for three SNPs. The evidence for ADAM33 and BHR and for an age-specific effect of two SNPs in DPP10 and asthma was weaker. Conclusion This study provides further evidence for an effect of NPSR1 on asthma, atopy and atopic asthma. In addition, this analysis suggests a role for NPSR1 in early-onset asthma driven by the strong effect of this gene on atopic asthma.
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- Timm, S., et al.
(författare)
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Place of upbringing in early childhood as related to inflammatory bowel diseases in adulthood: a population-based cohort study in Northern Europe
- 2014
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 29:6, s. 429-437
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Tidskriftsartikel (refereegranskat)abstract
- Background The two inflammatory bowel diseases (IBD), ulcerative colitis and Crohn's disease, has increased rapidly during the twentieth century, but the aetiology is still poorly understood. Impaired immunological competence due to decreasing biodiversity and altered microbial stimulation is a suggested explanation. Objective Place of upbringing was used as a proxy for the level and diversity of microbial stimulation to investigate the effects on the prevalence of IBD in adulthood. Methods Respiratory Health in Northern Europe (RHINE) III is a postal follow-up questionnaire of the European Community Respiratory Health Survey (ECRHS) cohorts established in 1989-1992. The study population was 10,864 subjects born 1945-1971 in Denmark, Norway, Sweden, Iceland and Estonia, who responded to questionnaires in 2000-2002 and 2010-2012. Data were analysed in logistic and Cox regression models taking age, sex, smoking and body mass index into consideration. Results Being born and raised on a livestock farm the first 5 years of life was associated with a lower risk of IBD compared to city living in logistic (OR 0.54, 95 % CI 0.31; 0.94) and Cox regression models (HR 0.55, 95 % CI 0.31; 0.98). Random-effect meta-analysis did not identify geographical difference in this association. Furthermore, there was a significant trend comparing livestock farm living, village and city living (p < 0.01). Sub-analyses showed that the protective effect was only present among subjects born after 1952 (OR 0.25, 95 % CI 0.11; 0.61). Conclusion This study suggests a protective effect from livestock farm living in early childhood on the occurrence of IBD in adulthood, however only among subjects born after 1952. We speculate that lower microbial diversity is an explanation for the findings.
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