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- Dijk, FN, et al.
(author)
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Genetic regulation of IL1RL1 methylation and IL1RL1-a protein levels in asthma
- 2018
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 51:3
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Journal article (peer-reviewed)abstract
- Interleukin-1 receptor–like 1 (IL1RL1) is an important asthma gene. (Epi)genetic regulation of IL1RL1 protein expression has not been established. We assessed the association between IL1RL1 single nucleotide polymorphisms (SNPs), IL1RL1 methylation and serum IL1RL1-a protein levels, and aimed to identify causal pathways in asthma.Associations of IL1RL1 SNPs with asthma were determined in the Dutch Asthma Genome-wide Association Study cohort and three European birth cohorts, BAMSE (Children/Barn, Allergy, Milieu, Stockholm, an Epidemiological survey), INMA (Infancia y Medio Ambiente) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy), participating in the Mechanisms of the Development of Allergy study. We performed blood DNA IL1RL1 methylation quantitative trait locus (QTL) analysis (n=496) and (epi)genome-wide protein QTL analysis on serum IL1RL1-a levels (n=1462). We investigated the association of IL1RL1 CpG methylation with asthma (n=632) and IL1RL1-a levels (n=548), with subsequent causal inference testing. Finally, we determined the association of IL1RL1-a levels with asthma and its clinical characteristics (n=1101).IL1RL1 asthma-risk SNPs strongly associated with IL1RL1 methylation (rs1420101; p=3.7×10−16) and serum IL1RL1-a levels (p=2.8×10−56). IL1RL1 methylation was not associated with asthma or IL1RL1-a levels. IL1RL1-a levels negatively correlated with blood eosinophil counts, whereas there was no association between IL1RL1-a levels and asthma.In conclusion, asthma-associated IL1RL1 SNPs strongly regulate IL1RL1 methylation and serum IL1RL1-a levels, yet neither these IL1RL1-methylation CpG sites nor IL1RL1-a levels are associated with asthma.
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- Ekman, A, et al.
(author)
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Swedish Clean Air and Climate Research Programme – SCAC Final report second phase
- 2020
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Reports (other academic/artistic)abstract
- The SCAC-2 program was initiated to provide an extended scientific knowledge base in national and international discussions and negotiations on the development of new air pollution policies and measures. Specifically, the program was focused on four main areas where additional knowledge was needed to support further actions: air pollution and climate interactions and hemispheric transport; air pollution and human health with focus on particles from transport and domestic wood burning; ecosystem effects (and air pollution – climate interactions) of ozone and nitrogen, the latter with emphasis on national nitrogen budgets and biodiversity. Finally, integrated assessment modelling and identification of the most efficient abatement strategies was included.
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| 16. |
- Enoksson Wallas, A., et al.
(author)
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Traffic noise and other determinants of blood pressure in adolescence
- 2019
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In: International Journal of Hygiene and Environmental Health. - : Elsevier BV. - 1438-4639 .- 1618-131X. ; 222:5, s. 824-830
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Journal article (peer-reviewed)abstract
- Background: Exposure to traffic noise has been associated with hypertension in adults but the evidence in adolescents is limited. We investigated long-term road traffic noise exposure, maternal occupational noise during pregnancy and other factors in relation to blood pressure and prehypertension at 16 years of age. Methods: Systolic and diastolic blood pressure were measured in 2597 adolescents from the Swedish BAMSE birth cohort. Levels of road traffic noise were estimated at home addresses during lifetime and for the mother during pregnancy as well as maternal occupational noise exposure during pregnancy. Exposure to NO x from local sources was also assessed. Associations between noise or NO x exposure and blood pressure or prehypertension were analysed using linear and logistic regression. Results: The prevalence of prehypertension was higher among males and in those with overweight, low physical activity or overweight mothers. No strong or consistent associations were observed between pre- or postnatal exposure to road traffic noise and blood pressure at 16 years of age. However, inverse associations were suggested for systolic or diastolic blood pressure and prehypertension, which reached statistical significance among males (OR 0.80 per 10 dB L den , 95% CI 0.65–0.99) and those with maternal occupational noise exposure ≥ 70 dB L Aeq8h (OR 0.60, 95% CI 0.41–0.87). On the other hand, occupational noise exposure during pregnancy tended to increase systolic blood pressure and prehypertension risk in adolescence. No associations were seen for NO x exposure. Conclusion: No conclusive associations were observed between pre- or postnatal noise exposure and blood pressure or prehypertension in adolescents. © 2019
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- Gref, A, et al.
(author)
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Dietary total antioxidant capacity in early school age and subsequent allergic disease.
- 2017
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 47:6, s. 751-759
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Journal article (peer-reviewed)abstract
- BACKGROUND: Dietary antioxidant intake has been hypothesized to influence the development of allergic diseases; however, few prospective studies have investigated this association.OBJECTIVE: Our aim was to study the association between total antioxidant capacity (TAC) of the diet at age 8 years and the subsequent development of asthma, rhinitis and sensitization to inhalant allergens between 8 and 16 years, and to assess potential effect modification by known risk factors.METHODS: A total of 2359 children from the Swedish birth cohort BAMSE were included. Dietary TAC at age 8 years was estimated by combining information on the child's diet the past 12 months from a food frequency questionnaire with a database of common foods analysed with the oxygen radical absorbance capacity method. Classification of asthma and rhinitis was based on questionnaires, and serum IgE antibodies were measured at 8 and 16 years.RESULTS: A statistically significant inverse association was observed between TAC of the diet and incident sensitization to inhalant allergens (adjusted odds ratio: 0.73, 95% confidence interval: 0.55-0.97 for the third compared to the first tertile, P-value for trend = 0.031). Effect modification by traffic-related air pollution exposure was observed, with a stronger association between dietary TAC and sensitization among children with low traffic-related air pollution exposure (P-value for interaction = 0.029). There was no evidence for effect modification by GSTP1 or TNF genotypes, although these results should be interpreted with caution. No clear associations were observed between TAC and development of rhinitis or asthma, although a significant inverse association was observed for allergic asthma (ORadj 0.57, 95% CI 0.34-0.94).CONCLUSIONS AND CLINICAL RELEVANCE: Higher TAC of the diet in early school age may decrease the risk of developing sensitization to inhalant allergens from childhood to adolescence. These findings indicate that implementing an antioxidant-rich diet in childhood may contribute to the prevention of allergic disease.
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- Gruzieva, O, et al.
(author)
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Air pollution, metabolites and respiratory health across the life-course
- 2022
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In: European respiratory review : an official journal of the European Respiratory Society. - : European Respiratory Society (ERS). - 1600-0617. ; 31:165
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Journal article (peer-reviewed)abstract
- Previous studies have explored the relationships of air pollution and metabolic profiles with lung function. However, the metabolites linking air pollution and lung function and the associated mechanisms have not been reviewed from a life-course perspective. Here, we provide a narrative review summarising recent evidence on the associations of metabolic profiles with air pollution exposure and lung function in children and adults. Twenty-six studies identified through a systematic PubMed search were included with 10 studies analysing air pollution-related metabolic profiles and 16 studies analysing lung function-related metabolic profiles. A wide range of metabolites were associated with short- and long-term exposure, partly overlapping with those linked to lung function in the general population and with respiratory diseases such as asthma and COPD. The existing studies show that metabolomics offers the potential to identify biomarkers linked to both environmental exposures and respiratory outcomes, but many studies suffer from small sample sizes, cross-sectional designs, a preponderance on adult lung function, heterogeneity in exposure assessment, lack of confounding control and omics integration. The ongoing EXposome Powered tools for healthy living in urbAN Settings (EXPANSE) project aims to address some of these shortcomings by combining biospecimens from large European cohorts and harmonised air pollution exposure and exposome data.
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| 27. |
- Gruzieva, O, et al.
(author)
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An update on the epigenetics of asthma
- 2021
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In: Current opinion in allergy and clinical immunology. - 1473-6322. ; 21:2, s. 175-181
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Journal article (peer-reviewed)
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| 28. |
- Gruzieva, O, et al.
(author)
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DNA Methylation Trajectories During Pregnancy
- 2019
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In: Epigenetics insights. - : SAGE Publications. - 2516-8657. ; 12, s. 2516865719867090-
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Journal article (peer-reviewed)abstract
- There is emerging evidence on DNA methylation (DNAm) variability over time; however, little is known about dynamics of DNAm patterns during pregnancy. We performed an epigenome-wide longitudinal DNAm study of a well-characterized sample of young women from the Swedish Born into Life study, with repeated blood sampling before, during and after pregnancy (n = 21), using the Illumina Infinium MethylationEPIC array. We conducted a replication in the Isle of Wight third-generation birth cohort (n = 27), using the Infinium HumanMethylation450k BeadChip. We identified 196 CpG sites displaying intra-individual longitudinal change in DNAm with a false discovery rate (FDR) P < .05. Most of these (91%) showed a decrease in average methylation levels over the studied period. We observed several genes represented by ⩾3 differentially methylated CpGs: HOXB3, AVP, LOC100996291, and MicroRNA 10a. Of 36 CpGs available in the replication cohort, 17 were replicated, all but 2 with the same direction of association (replication P < .05). Biological pathway analysis demonstrated that FDR-significant CpGs belong to genes overrepresented in metabolism-related pathways, such as adipose tissue development, regulation of insulin receptor signaling, and mammary gland fat development. These results contribute to a better understanding of the biological mechanisms underlying important physiological alterations and adaptations for pregnancy and lactation.
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| 38. |
- Jiang, YL, et al.
(author)
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Transcriptomics of atopy and atopic asthma in white blood cells from children and adolescents
- 2019
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 53:5
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Journal article (peer-reviewed)abstract
- Early allergic sensitisation (atopy) is the first step in the development of allergic diseases such as atopic asthma later in life. Genes and pathways associated with atopy and atopic asthma in children and adolescents have not been well characterised.A transcriptome-wide association study (TWAS) of atopy and atopic asthma in white blood cells (WBCs) or whole blood was conducted in a cohort of 460 Puerto Ricans aged 9–20 years (EVA-PR study) and in a cohort of 250 Swedish adolescents (BAMSE study). Pathway enrichment and network analyses were conducted to further assess top findings, and classification models of atopy and atopic asthma were built using expression levels for the top differentially expressed genes (DEGs).In a meta-analysis of the study cohorts, both previously implicated genes (e.g. IL5RA and IL1RL1) and genes not previously reported in TWASs (novel) were significantly associated with atopy and/or atopic asthma. Top novel genes for atopy included SIGLEC8 (p=8.07×10−13), SLC29A1 (p=7.07×10−12) and SMPD3 (p=1.48×10−11). Expression quantitative trait locus analyses identified multiple asthma-relevant genotype–expression pairs, such as rs2255888/ALOX15. Pathway enrichment analysis uncovered 16 significantly enriched pathways at adjusted p<0.01, including those relevant to T-helper cell type 1 (Th1) and Th2 immune responses. Classification models built using the top DEGs and a few demographic/parental history variables accurately differentiated subjects with atopic asthma from nonatopic control subjects (area under the curve 0.84).We have identified genes and pathways for atopy and atopic asthma in children and adolescents, using transcriptome-wide data from WBCs and whole blood samples.
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| 45. |
- Luo, R, et al.
(author)
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Paternal DNA Methylation May Be Associated With Gestational Age at Birth
- 2020
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In: Epigenetics insights. - : SAGE Publications. - 2516-8657. ; 13, s. 2516865720930701-
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Journal article (peer-reviewed)abstract
- How epigenetic modifications of DNA are associated with gestational age at birth is not fully understood. We investigated potential effects of differential paternal DNA methylation (DNAm) on offspring gestational age at birth by conducting an epigenome-wide search for cytosine-phosphate-guanine (CpG) sites. Methods: Study participants in this study consist of male cohort members or partners of the F1-generation of the Isle of Wight Birth Cohort (IoWBC). DNAm levels in peripheral blood from F1-fathers (n = 92) collected around pregnancy of their spouses were analyzed using the Illumina 450K array. A 5-step statistical analysis was performed. First, a training-testing screening approach was applied to select CpG sites that are potentially associated with gestational age at birth. Second, functional enrichment analysis was employed to identify biological processes. Third, by centralizing on biologically informative genes, Cox proportional hazards models were used to assess the hazard ratios of individual paternal CpGs on gestational age adjusting for confounders. Fourth, to assess the validity of our results, we compared our CpG-gestational age correlations within a Born into Life Study in Sweden (n = 15). Finally, we investigated the correlation between the detected CpGs and differential gene expression in F2 cord blood in the IoWBC. Results: Analysis of DNAm of fathers collected around their partner’s pregnancy identified 216 CpG sites significantly associated with gestational age at birth. Functional enrichment pathways analyses of the annotated genes revealed 2 biological pathways significantly related to cell-cell membrane adhesion molecules. Differential methylation of 9 cell membrane adhesion pathway-related CpGs were significantly associated with gestational age at birth after adjustment for confounders. The replication sample showed correlation coefficients of 2 pathway-related CpGs with gestational age at birth within 95% confidence intervals of correlation coefficients in IoWBC. Finally, CpG sites of protocadherin ( PCDH) gene clusters were associated with gene expression of PCDH in F2 cord blood. Conclusions: Our findings suggest that differential paternal DNAm may affect gestational age at birth through cell-cell membrane adhesion molecules. The results are novel but require future replication in a larger cohort.
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| 47. |
- Merid, Simon Kebede, et al.
(author)
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Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
- 2020
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In: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
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Journal article (peer-reviewed)abstract
- Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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| 48. |
- Molter, A, et al.
(author)
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A multicentre study of air pollution exposure and childhood asthma prevalence: the ESCAPE project
- 2015
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 45:3, s. 610-624
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Journal article (peer-reviewed)abstract
- The aim of this study was to determine the effect of six traffic-related air pollution metrics (nitrogen dioxide, nitrogen oxides, particulate matter with an aerodynamic diameter <10 μm (PM10), PM2.5, coarse particulate matter and PM2.5 absorbance) on childhood asthma and wheeze prevalence in five European birth cohorts: MAAS (England, UK), BAMSE (Sweden), PIAMA (the Netherlands), GINI and LISA (both Germany, divided into north and south areas).Land-use regression models were developed for each study area and used to estimate outdoor air pollution exposure at the home address of each child. Information on asthma and current wheeze prevalence at the ages of 4–5 and 8–10 years was collected using validated questionnaires. Multiple logistic regression was used to analyse the association between pollutant exposure and asthma within each cohort. Random-effects meta-analyses were used to combine effect estimates from individual cohorts.The meta-analyses showed no significant association between asthma prevalence and air pollution exposure (e.g. adjusted OR (95%CI) for asthma at age 8–10 years and exposure at the birth address (n=10377): 1.10 (0.81–1.49) per 10 μg·m-3 nitrogen dioxide; 0.88 (0.63–1.24) per 10 μg·m-3 PM10; 1.23 (0.78–1.95) per 5 μg·m-3 PM2.5). This result was consistently found in initial crude models, adjusted models and further sensitivity analyses.This study found no significant association between air pollution exposure and childhood asthma prevalence in five European birth cohorts.
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