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| 2. |
- Hancock, Dana B, et al.
(författare)
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Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function
- 2012
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 8:12, s. e1003098-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest PJMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest PJMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest PJMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.
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| 3. |
- 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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| 4. |
- Frisch, M, et al.
(författare)
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Cultural bias in the AAP's 2012 Technical Report and Policy Statement on male circumcision
- 2013
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 131:4, s. 796-800
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Tidskriftsartikel (refereegranskat)abstract
- The American Academy of Pediatrics recently released its new Technical Report and Policy Statement on male circumcision, concluding that current evidence indicates that the health benefits of newborn male circumcision outweigh the risks. The technical report is based on the scrutiny of a large number of complex scientific articles. Therefore, while striving for objectivity, the conclusions drawn by the 8 task force members reflect what these individual physicians perceived as trustworthy evidence. Seen from the outside, cultural bias reflecting the normality of nontherapeutic male circumcision in the United States seems obvious, and the report’s conclusions are different from those reached by physicians in other parts of the Western world, including Europe, Canada, and Australia. In this commentary, a different view is presented by non–US-based physicians and representatives of general medical associations and societies for pediatrics, pediatric surgery, and pediatric urology in Northern Europe. To these authors, only 1 of the arguments put forward by the American Academy of Pediatrics has some theoretical relevance in relation to infant male circumcision; namely, the possible protection against urinary tract infections in infant boys, which can easily be treated with antibiotics without tissue loss. The other claimed health benefits, including protection against HIV/AIDS, genital herpes, genital warts, and penile cancer, are questionable, weak, and likely to have little public health relevance in a Western context, and they do not represent compelling reasons for surgery before boys are old enough to decide for themselves.
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| 5. |
- Tomassen, P., et al.
(författare)
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Staphylococcus aureus enterotoxin-specific IgE is associated with asthma in the general population : a GA(2)LEN study
- 2013
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 68:10, s. 1289-1297
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSpecific IgE to Staphylococcus aureus enterotoxins (SE-IgE) has been associated with asthma. In the general population, we aimed to determine the prevalence of and risk factors for serum SE-IgE and to examine the association with asthma.MethodsA postal questionnaire was sent to a random sample of adults in 19 centers across Europe. A random sample of respondents was invited for clinical examination upon which they answered a questionnaire, underwent skin prick tests (SPTs) for common aeroallergens, and provided blood for measurement of total IgE and SE-IgE. Risks were analyzed within centers using weighted logistic regression, and overall estimates calculated using fixed-effects meta-analysis.Results2908 subjects were included in this analysis. Prevalence of positive SE-IgE was 29.3%; no significant geographic variation was observed. In contrast to positive skin prick tests, SE-IgE was more common in smokers (<15 pack-year: OR 1.11, P=0.079, 15 pack-year: OR 1.70, P<0.001), and prevalence did not decrease in older age-groups or in those with many siblings. Total IgE concentrations were higher in those with positive SE-IgE than in those with positive SPT. SE-IgE was associated with asthma (OR 2.10, 95% confidence interval [1.60-2.76], P=0.001) in a concentration-dependent manner. This effect was independent of SPT result and homogeneous across all centers.ConclusionsWe report for the first time that SE-IgE is common in the general population throughout Europe and that its risk factors differ from those of IgE against aeroallergens. This is the first study to show that SE-IgE is significantly and independently associated with asthma in the general population.
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| 7. |
- Anto, J. M., et al.
(författare)
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Risk factors of new-onset asthma in adults : a population-based international cohort study
- 2010
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 65:8, s. 1021-1030
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Tidskriftsartikel (refereegranskat)abstract
- P>Background: The occurrence of new-onset asthma during adulthood is common, but there is insufficient understanding of its determinants including the role of atopy. Objective: To assess the risk factors for the development of new-onset asthma in middle-aged adults and to compare them according to atopy. Methods: A longitudinal analysis of 9175 young adults who participated in two surveys of the European Community Respiratory Health Survey (ECRHS) conducted 9 years apart. Findings: We observed 179 cases of new-onset asthma among 4588 participants who were free of asthma and reported at the beginning of the follow-up that they had never had asthma (4.5 per 1000 person-years). In a logistic regression, the following risk factors were found to increase the risk of new-onset asthma: female gender (OR: 1.97; 95% confidence interval (CI): 1.38,2.81), bronchial hyperresponsiveness (3.25; 2.19,4.83), atopy (1.55;1.08,2.21), FEV1 < 100 % predicted (1.87;1.34,2.62), nasal allergy (1.98;1.39,2.84) and maternal asthma (1.91;1.13;3.21). Obesity, respiratory infections in early life and high-risk occupations increased the risk of new-onset asthma although we had limited power to confirm their role. Among the atopics, total IgE and sensitization to cat were independently related to the risk of new-onset asthma. The proportion of new-onset asthma attributable to atopy varied from 12% to 21%. Conclusion: Adults reporting that they had never had asthma were at a substantial risk of new-onset asthma as a result of multiple independent risk factors including lung function. Atopy explains a small proportion of new-onset adult asthma.
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| 9. |
- 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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| 10. |
- Newson, R B, et al.
(författare)
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Geographical variation in the prevalence of sensitization to common aeroallergens in adults : the GA2LEN survey
- 2014
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 69:5, s. 643-651
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Geographical variation in the prevalence of sensitization to aeroallergens may reflect differences in exposure to risk factors such as having older siblings, being raised on a farm or other unidentified exposures.OBJECTIVE: We wanted to measure geographical variation in skin prick test positivity and assess whether it was explained by differences in family size and/or farm exposure. We also compared prevalence in younger and older subjects.METHODS: Within the Global Allergy and Asthma European Network (GA(2) LEN) survey, we measured the prevalence of skin prick positivity to a panel of allergens, and geometric mean serum total immunoglobulin E (IgE), in 3451 participants aged 18-75 years in 13 areas of Europe. Estimated prevalence was standardized to account for study design. We compared prevalence estimates in younger and older subjects and further adjusted for age, gender, smoking history, farm exposure, number of older siblings and body mass index (BMI).RESULTS: Skin prick test positivity to any one of the measured allergens varied within Europe from 31.4% to 52.9%. Prevalence of sensitization to single allergens also varied. Variation in serum total IgE was less marked. Younger participants had higher skin prick sensitivity prevalence, but not total IgE, than older participants. Geographical variation remained even after adjustment for confounders.CONCLUSION: Geographical variation in the prevalence of skin prick test positivity in Europe is unlikely to be explained by geographical variation in gender, age, smoking history, farm exposure, family size and BMI. Higher prevalence in younger, compared to older, adults may reflect cohort-associated increases in sensitization or the influence of ageing on immune or tissue responses.
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