BackgroundThe aim of this study was to explore the natural history of peanut allergy in childhood... more BackgroundThe aim of this study was to explore the natural history of peanut allergy in childhood in two birth cohorts from the same geographical region in the South of England.MethodsThe FAIR birth cohort was established on the Isle of Wight (UK) between 2001 and 2002 (n = 969). Children were followed up prospectively, skin prick tested (SPT) to peanut allergens at 1, 2, 3 and 10 years and food challenges performed. The Isle of Wight (IOW) birth cohort was established in 1989 (n = 1456). SPTs were performed at 1, 2, 4 and 10 years. Peanut allergy was based on positive SPT and a good clinical history.ResultsIn the FAIR cohort, the prevalence of sensitization to peanut was 0.4%, 2.0%, 2.0% and 2.4% at 1, 2, 3 and 10 years, respectively. At 10 years of age, 12 of 828 (1.5%) children were diagnosed with peanut allergy. One child (8%) outgrew her peanut allergy between 3 and 10 years and two children (15%) presented with new onset peanut allergy. Over the first 10 years of life, 13 of 9...
Background: To investigate the intergenerational effects of grandmaternal smoking during pregnanc... more Background: To investigate the intergenerational effects of grandmaternal smoking during pregnancy (GMSDP) on the DNA methylation of grandchildren. Methods: Data from the Isle of Wight birth cohort with information regarding GMSDP and DNA methylation profiling at the birth of grandchildren (n = 161) were used. Differentially methylated CpG sites related to GMSDP were identified using testing–training screening, analysis of variance and multivariate analysis of covariance. The association between identified CpG sites and expression levels of neighboring genes was tested by linear regression. Results: Twenty-three CpG sites were differentially methylated in grandchildren because of GMSDP, and eight of these were associated with expression levels of 13 neighboring genes. Conclusion: GMSDP has an intergenerational effect on the DNA methylation profile of grandchildren independent of maternal smoking during pregnancy.
Introduction: Maternal (M) and grandmaternal (GM) gestational smoking increase the risk of wheeze... more Introduction: Maternal (M) and grandmaternal (GM) gestational smoking increase the risk of wheeze in offspring. The aryl-hydrocarbon receptor repressor (AHRR) is involved in detoxification of tobacco smoke compounds. DNA methylation (DNA-M) at AHRR CpG site cg05575921 is lower on exposure to smoking. Aims: Proof-of-concept showing the role of DNA methylation in transgenerational effects of smoking. Effect of M and GM smoking on methlyation of AHRR cg05575921 in cord blood. Methods: The Isle of Wight birth cohort is an unselected birth cohort 1989-90 ( n =1456), children of the cohort were recruited in a third generation study. Smoking in pregnancy by M and GM during pregnancy was collected prospectively. The effect of gestational smoking on cg05575921 in F 2 cord blood ( n =96) was assessed by linear regression analysis. Results: DNA-M at cg05575921 was hypomethylated with either M or GM gestational smoking, though the effect of both M and GM smoking was greater. Infants exposed to both M and GM smoking had significantly lower cg05575921 methylation than unexposed infants (p= 0.002). Conclusion: Study shows that transgenerational gestational smoking influences cg05575921 methylation, the consequences of gestational smoking may compound across generations. Further studies are needed to confirm the role of epigenetics in transgenerational effects of environmental exposures.
Background: Gestational smoking is associated with eczema and asthma during adolescence. Prior st... more Background: Gestational smoking is associated with eczema and asthma during adolescence. Prior studies have shown that gestational smoking reduces the DNA methylation (DNA-M) of AHRR (Aryl-Hydrocarbon Receptor Repressor) CpG (cytosine-phosphate-guanine) sites. Objective: To assess the interaction of DNA-M of AHRR CpG cg05575921 and gestational smoking for the risk asthma and eczema in boys and girls at age 18. Methods: Blood samples, asthma and eczema status were obtained at age 18 from the Isle of Wight birth cohort, UK. Maternal smoking was ascertained at birth. DNA-M was assessed by Illumina Infinium HumanMethylation450 array. Using linear regression, residuals were calculated by excluding the effect of gestational smoking on DNA-M at cg05575921. Log-linear models were used to test interaction of residuals and gestational smoking with eczema and asthma. Results: At age 18, 10.3% of boys (n=648) and 10.1% of girls (n=653) had eczema if the mother smoked during pregnancy; and 7.8% of boys and 18.0% girls had eczema if the mother did not ( p -value 0.32 in boys; 0.02 in girls). In contrast, for asthma, the respective proportions in the same order were, 11.2% boys (n=643) and 21.4% girls (n=656); and 17.2% boys and 18.9% girls ( p -value 0.08 in boys; 0.49 in girls). The interaction of residuals and gestational smoking was significantly associated with eczema but not with asthma. The relative risk of eczema is 0.4 times lower when methylation of cg05575921 was higher and the mother smoked during pregnancy. Conclusion: AHRR DNA-M may explain the trend of eczema in boys and girls with gestational smoking. Future analysis should explore the pathway by which AHRR is associated with eczema.
Season of birth influences allergy risk, however the biological mechanisms underlying this observ... more Season of birth influences allergy risk, however the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long-lasting effects on gene expression and disease. This study examined whether DNA methylation could underlie the association between season of birth and allergy. In a subset of 18-year-old participants from the Isle of Wight (IoW) birth cohort (n=367), the risks of birth season on allergic outcomes were estimated. Whole blood epigenome-wide DNA methylation was measured, and season-associated CpGs detected using a training-and-testing-based technique. Validation examined the 8-year-old Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. The relationships between DNA methylation, season of birth and allergy were examined. CpGs were analysed in IoW third generation cohort newborns. Autumn birth increased risk of eczema, relative to spring birth. Methylation at 92 CpGs showed association with seas...
SummaryBackgroundWhile the prevalence of asthma in children is decreasing or remaining the same, ... more SummaryBackgroundWhile the prevalence of asthma in children is decreasing or remaining the same, time trends in the prevalence of rhinitis in children are not known. Understanding sensitisation trends may help inform about trends in asthma and rhinitis prevalence.ObjectiveTo assess time trends of wheeze, rhinitis and aero‐allergen sensitisation prevalence at 10 years of age, we compared two birth cohorts established 12 years apart. To gain insight into differences in disease prevalence, we assessed association of family history, early life exposures and sensitisation with wheeze and rhinitis in each cohort.MethodsThe IoW (Isle of Wight) and FAIR (Food Allergy and Intolerance Research) unselected birth cohorts were established in 1989 and 2001 respectively in IoW. Identical ISAAC questionnaire and skin prick test data were collected and compared at 10 years of age.ResultsOver the 12‐year period from 2001 to 2012, prevalence of lifetime wheeze, current wheeze and those ever treated fo...
BackgroundThe aim of this study was to explore the natural history of peanut allergy in childhood... more BackgroundThe aim of this study was to explore the natural history of peanut allergy in childhood in two birth cohorts from the same geographical region in the South of England.MethodsThe FAIR birth cohort was established on the Isle of Wight (UK) between 2001 and 2002 (n = 969). Children were followed up prospectively, skin prick tested (SPT) to peanut allergens at 1, 2, 3 and 10 years and food challenges performed. The Isle of Wight (IOW) birth cohort was established in 1989 (n = 1456). SPTs were performed at 1, 2, 4 and 10 years. Peanut allergy was based on positive SPT and a good clinical history.ResultsIn the FAIR cohort, the prevalence of sensitization to peanut was 0.4%, 2.0%, 2.0% and 2.4% at 1, 2, 3 and 10 years, respectively. At 10 years of age, 12 of 828 (1.5%) children were diagnosed with peanut allergy. One child (8%) outgrew her peanut allergy between 3 and 10 years and two children (15%) presented with new onset peanut allergy. Over the first 10 years of life, 13 of 9...
Background: To investigate the intergenerational effects of grandmaternal smoking during pregnanc... more Background: To investigate the intergenerational effects of grandmaternal smoking during pregnancy (GMSDP) on the DNA methylation of grandchildren. Methods: Data from the Isle of Wight birth cohort with information regarding GMSDP and DNA methylation profiling at the birth of grandchildren (n = 161) were used. Differentially methylated CpG sites related to GMSDP were identified using testing–training screening, analysis of variance and multivariate analysis of covariance. The association between identified CpG sites and expression levels of neighboring genes was tested by linear regression. Results: Twenty-three CpG sites were differentially methylated in grandchildren because of GMSDP, and eight of these were associated with expression levels of 13 neighboring genes. Conclusion: GMSDP has an intergenerational effect on the DNA methylation profile of grandchildren independent of maternal smoking during pregnancy.
Introduction: Maternal (M) and grandmaternal (GM) gestational smoking increase the risk of wheeze... more Introduction: Maternal (M) and grandmaternal (GM) gestational smoking increase the risk of wheeze in offspring. The aryl-hydrocarbon receptor repressor (AHRR) is involved in detoxification of tobacco smoke compounds. DNA methylation (DNA-M) at AHRR CpG site cg05575921 is lower on exposure to smoking. Aims: Proof-of-concept showing the role of DNA methylation in transgenerational effects of smoking. Effect of M and GM smoking on methlyation of AHRR cg05575921 in cord blood. Methods: The Isle of Wight birth cohort is an unselected birth cohort 1989-90 ( n =1456), children of the cohort were recruited in a third generation study. Smoking in pregnancy by M and GM during pregnancy was collected prospectively. The effect of gestational smoking on cg05575921 in F 2 cord blood ( n =96) was assessed by linear regression analysis. Results: DNA-M at cg05575921 was hypomethylated with either M or GM gestational smoking, though the effect of both M and GM smoking was greater. Infants exposed to both M and GM smoking had significantly lower cg05575921 methylation than unexposed infants (p= 0.002). Conclusion: Study shows that transgenerational gestational smoking influences cg05575921 methylation, the consequences of gestational smoking may compound across generations. Further studies are needed to confirm the role of epigenetics in transgenerational effects of environmental exposures.
Background: Gestational smoking is associated with eczema and asthma during adolescence. Prior st... more Background: Gestational smoking is associated with eczema and asthma during adolescence. Prior studies have shown that gestational smoking reduces the DNA methylation (DNA-M) of AHRR (Aryl-Hydrocarbon Receptor Repressor) CpG (cytosine-phosphate-guanine) sites. Objective: To assess the interaction of DNA-M of AHRR CpG cg05575921 and gestational smoking for the risk asthma and eczema in boys and girls at age 18. Methods: Blood samples, asthma and eczema status were obtained at age 18 from the Isle of Wight birth cohort, UK. Maternal smoking was ascertained at birth. DNA-M was assessed by Illumina Infinium HumanMethylation450 array. Using linear regression, residuals were calculated by excluding the effect of gestational smoking on DNA-M at cg05575921. Log-linear models were used to test interaction of residuals and gestational smoking with eczema and asthma. Results: At age 18, 10.3% of boys (n=648) and 10.1% of girls (n=653) had eczema if the mother smoked during pregnancy; and 7.8% of boys and 18.0% girls had eczema if the mother did not ( p -value 0.32 in boys; 0.02 in girls). In contrast, for asthma, the respective proportions in the same order were, 11.2% boys (n=643) and 21.4% girls (n=656); and 17.2% boys and 18.9% girls ( p -value 0.08 in boys; 0.49 in girls). The interaction of residuals and gestational smoking was significantly associated with eczema but not with asthma. The relative risk of eczema is 0.4 times lower when methylation of cg05575921 was higher and the mother smoked during pregnancy. Conclusion: AHRR DNA-M may explain the trend of eczema in boys and girls with gestational smoking. Future analysis should explore the pathway by which AHRR is associated with eczema.
Season of birth influences allergy risk, however the biological mechanisms underlying this observ... more Season of birth influences allergy risk, however the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long-lasting effects on gene expression and disease. This study examined whether DNA methylation could underlie the association between season of birth and allergy. In a subset of 18-year-old participants from the Isle of Wight (IoW) birth cohort (n=367), the risks of birth season on allergic outcomes were estimated. Whole blood epigenome-wide DNA methylation was measured, and season-associated CpGs detected using a training-and-testing-based technique. Validation examined the 8-year-old Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. The relationships between DNA methylation, season of birth and allergy were examined. CpGs were analysed in IoW third generation cohort newborns. Autumn birth increased risk of eczema, relative to spring birth. Methylation at 92 CpGs showed association with seas...
SummaryBackgroundWhile the prevalence of asthma in children is decreasing or remaining the same, ... more SummaryBackgroundWhile the prevalence of asthma in children is decreasing or remaining the same, time trends in the prevalence of rhinitis in children are not known. Understanding sensitisation trends may help inform about trends in asthma and rhinitis prevalence.ObjectiveTo assess time trends of wheeze, rhinitis and aero‐allergen sensitisation prevalence at 10 years of age, we compared two birth cohorts established 12 years apart. To gain insight into differences in disease prevalence, we assessed association of family history, early life exposures and sensitisation with wheeze and rhinitis in each cohort.MethodsThe IoW (Isle of Wight) and FAIR (Food Allergy and Intolerance Research) unselected birth cohorts were established in 1989 and 2001 respectively in IoW. Identical ISAAC questionnaire and skin prick test data were collected and compared at 10 years of age.ResultsOver the 12‐year period from 2001 to 2012, prevalence of lifetime wheeze, current wheeze and those ever treated fo...
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