Several studies have demonstrated that early intervention may modulate the natural course of atop... more Several studies have demonstrated that early intervention may modulate the natural course of atopic disease. Our objective was to prevent sensitization to house-dust mite and food allergens, as well as the development of atopic symptoms during infancy, by the combination of an educational package and the use of mite allergen-impermeable mattress encasings. A multicentre European, population-based, randomized, controlled study of children at increased atopic risk [Study on the Prevention of Allergy in Children in Europe (SPACE)] was performed in five countries (Austria, Germany, Greece, the UK, and Lithuania), and included three cohorts – schoolchildren, toddlers, and newborns. We report on the newborn cohort. A total of 696 newborns were included from Austria, the UK, and Germany. Inclusion criteria were: a positive history of parental allergy; and a positive skin-prick test or specific immunoglobulin E (IgE) (IgE ≥ 1.43 kU/L) against at least one out of a panel of common aeroallerg...
Several studies have demonstrated that early intervention may modulate the natural course of atop... more Several studies have demonstrated that early intervention may modulate the natural course of atopic disease. The objective of this study was to prevent sensitization to house dust mite and food allergens, as well as development of atopic symptoms, during infancy. To achieve this we employed the combination of an educational package with the use of mite allergen-impermeable mattress encasings. A multi-center European, population-based, randomized controlled study of children at increased atopic risk [study on the prevention of Allergy in Children in Europe (SPACE)] was performed in five countries (Austria, Germany, Greece, Great Britain, Lithuania) and included three cohorts of schoolchildren, toddlers and newborns. We report on the newborn cohort. A total of 696 newborns were included in Austria, Great Britain and Germany. Inclusion criteria were a positive history of parental allergy and a positive skin-prick test or specific immunoglobulin E (IgE) of >or= 1.43 kU/l against at l...
We created Asthma e-Lab, a secure web-based research environment to support consistent recording,... more We created Asthma e-Lab, a secure web-based research environment to support consistent recording, description and sharing of data, computational/statistical methods and emerging findings across the five UK birth cohorts. The e-Lab serves as a data repository for our unified dataset and provides the computational resources and a scientific social network to support collaborative research. All activities are transparent, and emerging findings are shared via the e-Lab, linked to explanations of analytical methods, thus enabling knowledge transfer. eLab facilitates the iterative interdisciplinary dialogue between clinicians, statisticians, computer scientists, mathematicians, geneticists and basic scientists, capturing collective thought behind the interpretations of findings.
International journal of molecular epidemiology and genetics, 2013
To determine whether DNA methylation (DNA-M) of the leptin receptor genotype (LEPR/LEPROT) links ... more To determine whether DNA methylation (DNA-M) of the leptin receptor genotype (LEPR/LEPROT) links gestational smoking and leptin serum levels and BMI later in life, we focused on female offspring, 18 years of age, from the Isle of Wight Birth Cohort (IOWBC). Leptin binds to the leptin receptor encoded by the LEPR/LEPROT genotype. Using general linear models, we tested a two-stage model. First, we investigated whether single nucleotide polymorphisms (SNPs) acting as methylation quantitative trait loci (methQTLs) depending on gestational smoking were related to differentially methylated cytosine-phosphate-guanine (CpG) sites. In stage 2, we tested whether the selected CpG sites, in interaction with other SNPs (modifiable genetic variants, modGV), are associated with serum leptin and BMI (stage 2). Children from the IOWBC were followed from birth to age 18. Information on gestational smoking was gathered upon delivery. SNPs tagging LEPR and LEPROT genes were genotyped. Data on LEPR/LEPR...
Asthma is a chronic disease that often starts in childhood. The key risk factors are a child'... more Asthma is a chronic disease that often starts in childhood. The key risk factors are a child's environment and their genetic characteristics. The aim of this study was to evaluate the efficacy of environmental modification in the first 12 months of life on the prevalence of asthma in high-risk individuals. Children (n=120) considered at high risk of allergic disorders (either dual heredity or single heredity and a high cord total IgE), were enrolled in a single-blinded, randomised controlled trial. Infants in the intervention arm were either breast fed with the mother on a low allergen diet or given an extensively hydrolysed formula. Exposure to house dust mite allergen was reduced. The control group followed standard advice. Children were assessed at ages 1, 2, 4, 8 and 18 years for the presence of asthma and atopy. At 18 years of age, there was a significantly lower prevalence of asthma in the prevention group compared with the control group (OR: 0.23, 95% CI 0.08 to 0.70, p=0...
The protective effects of breastfeeding on early life respiratory infections are established, but... more The protective effects of breastfeeding on early life respiratory infections are established, but there have been conflicting reports on protection from asthma in late childhood. The association of breastfeeding duration and lung function was assessed in 10-year-old children. In the Isle of Wight birth cohort (n = 1456), breastfeeding practices and duration were prospectively assessed at birth and at subsequent follow-up visits (1 and 2 years). Breastfeeding duration was categorised as "not breastfed" (n = 196); "<2 months" (n = 243); "2 to <4 months" (n = 142) and ">or=4 months" (n = 374). Lung function was measured at age 10 years (n = 1033): forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)), FEV(1)/FVC ratio and peak expiratory flow (PEF). Maternal history of asthma and allergy was assessed at birth. The effect of breastfeeding on lung function was analysed using general linear models, adjusting for birth weight...
There is a great body of evidence that siblings have a protective effect against atopic manifesta... more There is a great body of evidence that siblings have a protective effect against atopic manifestations such as hay fever, atopic eczema, allergic sensitization, or asthma. Factors that may explain this association remain largely unknown. One hypothesis is that siblings promote early infections in childhood, and repeated infections protect against atopic disorders. Another hypothesis, the potential in utero programming, has
Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic f... more Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic factors including DNA methylation. We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989. Logistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18...
Several studies have demonstrated that early intervention may modulate the natural course of atop... more Several studies have demonstrated that early intervention may modulate the natural course of atopic disease. Our objective was to prevent sensitization to house-dust mite and food allergens, as well as the development of atopic symptoms during infancy, by the combination of an educational package and the use of mite allergen-impermeable mattress encasings. A multicentre European, population-based, randomized, controlled study of children at increased atopic risk [Study on the Prevention of Allergy in Children in Europe (SPACE)] was performed in five countries (Austria, Germany, Greece, the UK, and Lithuania), and included three cohorts – schoolchildren, toddlers, and newborns. We report on the newborn cohort. A total of 696 newborns were included from Austria, the UK, and Germany. Inclusion criteria were: a positive history of parental allergy; and a positive skin-prick test or specific immunoglobulin E (IgE) (IgE ≥ 1.43 kU/L) against at least one out of a panel of common aeroallerg...
Several studies have demonstrated that early intervention may modulate the natural course of atop... more Several studies have demonstrated that early intervention may modulate the natural course of atopic disease. The objective of this study was to prevent sensitization to house dust mite and food allergens, as well as development of atopic symptoms, during infancy. To achieve this we employed the combination of an educational package with the use of mite allergen-impermeable mattress encasings. A multi-center European, population-based, randomized controlled study of children at increased atopic risk [study on the prevention of Allergy in Children in Europe (SPACE)] was performed in five countries (Austria, Germany, Greece, Great Britain, Lithuania) and included three cohorts of schoolchildren, toddlers and newborns. We report on the newborn cohort. A total of 696 newborns were included in Austria, Great Britain and Germany. Inclusion criteria were a positive history of parental allergy and a positive skin-prick test or specific immunoglobulin E (IgE) of >or= 1.43 kU/l against at l...
We created Asthma e-Lab, a secure web-based research environment to support consistent recording,... more We created Asthma e-Lab, a secure web-based research environment to support consistent recording, description and sharing of data, computational/statistical methods and emerging findings across the five UK birth cohorts. The e-Lab serves as a data repository for our unified dataset and provides the computational resources and a scientific social network to support collaborative research. All activities are transparent, and emerging findings are shared via the e-Lab, linked to explanations of analytical methods, thus enabling knowledge transfer. eLab facilitates the iterative interdisciplinary dialogue between clinicians, statisticians, computer scientists, mathematicians, geneticists and basic scientists, capturing collective thought behind the interpretations of findings.
International journal of molecular epidemiology and genetics, 2013
To determine whether DNA methylation (DNA-M) of the leptin receptor genotype (LEPR/LEPROT) links ... more To determine whether DNA methylation (DNA-M) of the leptin receptor genotype (LEPR/LEPROT) links gestational smoking and leptin serum levels and BMI later in life, we focused on female offspring, 18 years of age, from the Isle of Wight Birth Cohort (IOWBC). Leptin binds to the leptin receptor encoded by the LEPR/LEPROT genotype. Using general linear models, we tested a two-stage model. First, we investigated whether single nucleotide polymorphisms (SNPs) acting as methylation quantitative trait loci (methQTLs) depending on gestational smoking were related to differentially methylated cytosine-phosphate-guanine (CpG) sites. In stage 2, we tested whether the selected CpG sites, in interaction with other SNPs (modifiable genetic variants, modGV), are associated with serum leptin and BMI (stage 2). Children from the IOWBC were followed from birth to age 18. Information on gestational smoking was gathered upon delivery. SNPs tagging LEPR and LEPROT genes were genotyped. Data on LEPR/LEPR...
Asthma is a chronic disease that often starts in childhood. The key risk factors are a child'... more Asthma is a chronic disease that often starts in childhood. The key risk factors are a child's environment and their genetic characteristics. The aim of this study was to evaluate the efficacy of environmental modification in the first 12 months of life on the prevalence of asthma in high-risk individuals. Children (n=120) considered at high risk of allergic disorders (either dual heredity or single heredity and a high cord total IgE), were enrolled in a single-blinded, randomised controlled trial. Infants in the intervention arm were either breast fed with the mother on a low allergen diet or given an extensively hydrolysed formula. Exposure to house dust mite allergen was reduced. The control group followed standard advice. Children were assessed at ages 1, 2, 4, 8 and 18 years for the presence of asthma and atopy. At 18 years of age, there was a significantly lower prevalence of asthma in the prevention group compared with the control group (OR: 0.23, 95% CI 0.08 to 0.70, p=0...
The protective effects of breastfeeding on early life respiratory infections are established, but... more The protective effects of breastfeeding on early life respiratory infections are established, but there have been conflicting reports on protection from asthma in late childhood. The association of breastfeeding duration and lung function was assessed in 10-year-old children. In the Isle of Wight birth cohort (n = 1456), breastfeeding practices and duration were prospectively assessed at birth and at subsequent follow-up visits (1 and 2 years). Breastfeeding duration was categorised as "not breastfed" (n = 196); "<2 months" (n = 243); "2 to <4 months" (n = 142) and ">or=4 months" (n = 374). Lung function was measured at age 10 years (n = 1033): forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)), FEV(1)/FVC ratio and peak expiratory flow (PEF). Maternal history of asthma and allergy was assessed at birth. The effect of breastfeeding on lung function was analysed using general linear models, adjusting for birth weight...
There is a great body of evidence that siblings have a protective effect against atopic manifesta... more There is a great body of evidence that siblings have a protective effect against atopic manifestations such as hay fever, atopic eczema, allergic sensitization, or asthma. Factors that may explain this association remain largely unknown. One hypothesis is that siblings promote early infections in childhood, and repeated infections protect against atopic disorders. Another hypothesis, the potential in utero programming, has
Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic f... more Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic factors including DNA methylation. We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989. Logistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18...
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Papers by Hasan Arshad