| 1. |
- Loth, Daan W, et al.
(author)
-
Genome-wide association analysis identifies six new loci associated with forced vital capacity
- 2014
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
-
Journal article (peer-reviewed)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.
|
|
| 2. |
- Ballardini, Natalia, et al.
(author)
-
Development and comorbidity of eczema, asthma and rhinitis to age 12 : data from the BAMSE birth cohort
- 2012
-
In: Allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0105-4538 .- 1398-9995.
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Allergy-related diseases are a public health issue, but knowledge on development and comorbidity among children is scarce. The aim was to study the development of eczema, asthma and rhinitis in relation to sex and parental allergy, in a population-based cohort, during childhood. METHODS: At 1, 2, 4, 8 and 12 years, parental questionnaires were used to obtain data on allergy-related diseases. Complete data for all five follow-up occasions were available from 2916 children. Odds ratios for the risk of any allergy-related disease in relation to heredity and sex were calculated using generalized estimating equations. RESULTS: At 12 years, 58% of the children had had eczema, asthma and/or rhinitis at some time. Disease turnover was high for all three diseases throughout the study. Comorbidity increased with age, and at 12 years, 7.5% of all the children were affected by at least two allergy-related diseases. Parental allergy was associated with increased comorbidity and more persistent disease and increased the risk of having any allergy-related disease (adjusted OR 1.76; 95% CI 1.57-1.97) up to 12 years. Male sex was associated with an increased risk throughout childhood. Boys and girls did not differ in disease persistence, and for comorbidity, the differences were minor. CONCLUSIONS: Allergy-related diseases may affect a majority of children. Eczema, asthma and rhinitis develop dynamically throughout childhood, and allergic comorbidity is common. These findings indicate that allergy-related diseases should be neither seen nor studied as isolated entities.
|
|
| 3. |
- Bornelöv, Susanne, et al.
(author)
-
Rule-Based Models of the Interplay between Genetic and Environmental Factors in Childhood Allergy
- 2013
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11, s. e80080-
-
Journal article (peer-reviewed)abstract
- Both genetic and environmental factors are important for the development of allergic diseases. However, a detailed understanding of how such factors act together is lacking. To elucidate the interplay between genetic and environmental factors in allergic diseases, we used a novel bioinformatics approach that combines feature selection and machine learning. In two materials, PARSIFAL (a European cross-sectional study of 3113 children) and BAMSE (a Swedish birth-cohort including 2033 children), genetic variants as well as environmental and lifestyle factors were evaluated for their contribution to allergic phenotypes. Monte Carlo feature selection and rule based models were used to identify and rank rules describing how combinations of genetic and environmental factors affect the risk of allergic diseases. Novel interactions between genes were suggested and replicated, such as between ORMDL3 and RORA, where certain genotype combinations gave odds ratios for current asthma of 2.1 (95% CI 1.2-3.6) and 3.2 (95% CI 2.0-5.0) in the BAMSE and PARSIFAL children, respectively. Several combinations of environmental factors appeared to be important for the development of allergic disease in children. For example, use of baby formula and antibiotics early in life was associated with an odds ratio of 7.4 (95% CI 4.5-12.0) of developing asthma. Furthermore, genetic variants together with environmental factors seemed to play a role for allergic diseases, such as the use of antibiotics early in life and COL29A1 variants for asthma, and farm living and NPSR1 variants for allergic eczema. Overall, combinations of environmental and life style factors appeared more frequently in the models than combinations solely involving genes. In conclusion, a new bioinformatics approach is described for analyzing complex data, including extensive genetic and environmental information. Interactions identified with this approach could provide useful hints for further in-depth studies of etiological mechanisms and may also strengthen the basis for risk assessment and prevention.
|
|
| 4. |
- Hammar, Katarina Stenberg, et al.
(author)
-
Subnormal levels of vitamin D are associated with acute wheeze in young children
- 2014
-
In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 103:8, s. 856-861
-
Journal article (peer-reviewed)abstract
- Aim: This study evaluated risk factors for acute wheeze in preschool children and investigated whether subnormal levels of vitamin D were associated with increased risk for acute wheeze, atopy or viral/bacterial respiratory infections. Methods: We recruited 130 children with acute wheeze, aged 6 months to 4 years, from paediatric emergency departments in Stockholm, Sweden, and 101 age-matched controls with no history of wheeze or sensitisation to airborne allergens. Parents answered standardised questionnaires, and blood samples were analysed for specific IgE to airborne and food allergens and levels of 25 hydroxyvitamin D (25(OH)D). Nasopharyngeal virus samples were collected during the emergency department visit in the group of children with wheeze, and a subset were also tested for bacteria. Results: Vitamin D insufficiency (25(OH)D < 75 nmol/L (30 ng/mL)) was associated with an odds ratio of 2.7 (95% confidence interval 1.1-6.2) for acute wheeze. However, no association was found between vitamin D insufficiency and atopy, presence of virus or bacteria or recurrent infections. Children older than 24 months were particularly at risk of subnormal vitamin D levels, irrespective of wheezing history. Conclusion: Our findings support the hypothesis that subnormal levels of vitamin D are associated with acute wheeze in young children.
|
|
| 5. |
- Panasevich, Sviatlana, et al.
(author)
-
Investigation of novel genes for lung function in children and their interaction with tobacco smoke exposure : a preliminary report.
- 2013
-
In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 102:5, s. 498-503
-
Journal article (peer-reviewed)abstract
- AIM: To replicate newly reported single nucleotide polymorphism (SNP) associations with adult lung function in a cohort of children and to investigate interactions with tobacco smoke exposure on lung function.METHODS: Of 37 reported SNPs in adults, 21 were available in our genome-wide association study data set, either directly genotyped or as proxy SNPs. We tested for association with lung function (FEV1 , FVC, FEV1 /FVC%) in 8-year-old children and analysed interaction with tobacco smoke exposure both prenatally and/or during infancy, as well as at the age of 8 years.RESULTS: SNPs in TNS1, ADAM19, THSD4 and ADCY2 showed significant association with lung function in children, although ADCY2 variants not in the expected direction. For example, variant allele A in THSD4 rs12899618 was associated with 50.2 mL higher FEV1 (p = 0.007) and variant allele C in ADAM19 rs2277027 with 1% unit lower FEV1 /FVC% (p = 0.03) per allele. DAAM2 rs2395730 showed interaction with current tobacco smoke exposure, with variant C allele associated with 1.3% unit decrease in FEV1 /FVC% in exposed children, but not in unexposed (p for interaction 0.04).CONCLUSION: Our data replicate in children an association for TNS1, ADAM19, THSD4 and ADCY2 gene variants with lung function and suggest that interaction with tobacco smoke exposure may be of importance.
|
|
| 6. |
- Thacher, Jesse D., et al.
(author)
-
Pre- and Postnatal Exposure to Parental Smoking and Allergic Disease Through Adolescence
- 2014
-
In: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 134:3, s. 428-434
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: To examine the role of prenatal and postnatal second-hand tobacco smoke (SHS) exposure on asthma, rhinitis, and eczema development up to 16 years of age. METHODS: A birth cohort of 4089 children was followed for 16 years. Information on parental smoking habits, lifestyle factors, and symptoms of allergic disease was gathered using repeated parental questionnaires. Generalized estimating equations assessed the overall and age-specific associations between SHS exposure and allergic disease at ages 1 to 16 years. RESULTS: Exposure to SHS in utero was associated with an overall elevated risk of developing asthma up to 16 years (odds ratio [OR] = 1.45; 95% confidence interval [CI], 1.15-1.83) but not for rhinitis or eczema. After additional adjustment for parental smoking throughout childhood, excess overall risks for asthma remained statistically significant. Moreover, a dose-dependent pattern with SHS was observed. Exposure to SHS during infancy was associated with an overall elevated risk of asthma (OR = 1.23; 95% CI, 1.01-1.51), rhinitis (OR = 1.18; 95% CI, 1.01-1.39), and eczema (OR = 1.26; 95% CI, 1.09-1.45) up to 16 years. When age-specific associations were examined, the elevated risks related to SHS exposure in utero or during infancy were mostly confined to early childhood for asthma and rhinitis, whereas the excess risk of eczema appeared greatest at later ages. CONCLUSIONS: Our findings indicate that early SHS exposure, in utero or during infancy, influences the development of allergic disease up to adolescence. Excess risks for asthma and rhinitis were seen primarily in early childhood, whereas those for eczema occurred at later ages.
|
|
