Recent observations that disease risk can be transmitted across generations without the need for direct exposure of the child to the index environmental insult has sparked interest in ...transgenerational inheritance. Epigenetics describes processes that modify gene expression without a change in the nucleotide sequence. Epigenetic processes can be induced in response to environmental exposures, can influence disease risk, and might explain these multigenerational effects. In experimental models a number of epigenetic mechanisms have been identified that could mediate vertical transmission of epigenetic inheritance. However, relevance of these findings to human disease is not yet clear. An alternative model is one in which transgenerational inheritance of disease risk requires the presence of exposure-related diseases in the mother during pregnancy (termed induced epigenetic transmission model). A number of cross-sectional studies have investigated multigenerational effects in allergy and asthma. However, given the early-life origins of asthma and allergy, birth cohort studies are ideal to investigate the effect of genetic predisposition, epigenetics, and environmental exposures, avoiding pitfalls, such as recall bias and confounding by ongoing exposures, disease, and treatment. The well-characterized 3 generations of the Isle of Wight cohort include 2 consecutive birth cohorts, providing longitudinal data that can be studied for epigenetic transfer of information, such as the effect of grand parental smoking or exposure to other toxic compounds. Further large multigenerational birth cohorts are needed to establish the clinical relevance of this phenomenon and differentiate between vertical and induced transmission models, which might influence future preventive strategies.
Background The parent-of-origin effect is important in understanding the genetic basis of childhood allergic diseases and improving our ability to identify high-risk children. Objective We sought to ...investigate the parent-of-origin effect in childhood allergic diseases. Methods The Isle of Wight Birth Cohort (n = 1456) has been examined at 1, 2, 4, 10, and 18 years of age. Information on the prevalence of asthma, eczema, rhinitis, and environmental factors was obtained by using validated questionnaires. Skin prick tests were carried out at ages 4, 10, and 18 years, and total IgE measurement was carried out at 10 and 18 years. Parental history of allergic disease was assessed soon after the birth of the child, when maternal IgE levels were also measured. Prevalence ratios (PRs) and their 95% CIs were estimated, applying log-linear models adjusted for confounding variables. Results When stratified for sex of the child, maternal asthma was associated with asthma in girls (PR, 1.91; 95% CI, 1.34-2.72; P = .0003) but not in boys (PR, 1.29; 95% CI, 0.85-1.96; P = .23), whereas paternal asthma was associated with asthma in boys (PR, 1.99; 95% CI, 1.42-2.79; P < .0001) but not in girls (PR, 1.03; 95% CI, 0.59-1.80; P = .92). Maternal eczema increased the risk of eczema in girls (PR, 1.92; 95% CI, 1.37-2.68; P = .0001) only, whereas paternal eczema did the same for boys (PR, 2.07; 95% CI, 1.32-3.25; P = .002). Similar trends were observed when the effect of maternal and paternal allergic disease was assessed for childhood atopy and when maternal total IgE levels were related to total IgE levels in children at ages 10 and 18 years. Conclusions The current study indicates a sex-dependent association of parental allergic conditions with childhood allergies, with maternal allergy increasing the risk in girls and paternal allergy increasing the risk in boys. This has implications for childhood allergy prediction and prevention.
Background Rhinitis affects many young adults and often shows comorbidity with asthma. Objective We hypothesized that young adult rhinitis, like asthma, exhibits clinical heterogeneity identifiable ...by means of cluster analysis. Methods Participants in the Isle of Wight birth cohort (n = 1456) were assessed at 1, 2, 4, 10, and 18 years of age. Cluster analysis was performed on those with rhinitis at age 18 years (n = 468) by using 13 variables defining clinical characteristics. Results Four clusters were identified. Patients in cluster 1 (n = 128 27.4%; ie, moderate childhood-onset rhinitis) had high atopy and eczema prevalence and high total IgE levels but low asthma prevalence. They showed the best lung function at 18 years of age, with normal fraction of exhaled nitric oxide (F eno ), low bronchial hyperresponsiveness (BHR), and low bronchodilator reversibility (BDR) but high rhinitis symptoms and treatment. Patients in cluster 2 (n = 199 42.5%; ie, mild-adolescence-onset female rhinitis) had the lowest prevalence of comorbid atopy, asthma, and eczema. They had normal lung function and low BHR, BDR, F eno values, and total IgE levels plus low rhinitis symptoms, severity, and treatment. Patients in cluster 3 (n = 59 12.6%; ie, severe earliest-onset rhinitis with asthma) had the youngest rhinitis onset plus the highest comorbid asthma (of simultaneous onset) and atopy. They showed the most obstructed lung function with high BHR, BDR, and F eno values plus high rhinitis symptoms, severity, and treatment. Patient 4 in cluster 4 (n = 82 17.5%; ie, moderate childhood-onset male rhinitis with asthma) had high atopy, intermediate asthma, and low eczema. They had impaired lung function with high F eno values and total IgE levels but intermediate BHR and BDR. They had moderate rhinitis symptoms. Conclusion Clinically distinctive adolescent rhinitis clusters are apparent with varying sex and asthma associations plus differing rhinitis severity and treatment needs.
Methods A total of 48-cord blood samples from Taiwan Maternal and Infant Cohort Study were analyzed using the Infinium Human Beadchip to obtain DNA methylation at ~450K Cytosine-phosphate-Guanine ...(CpG) sites.
Conclusions The results suggest that gestational eczema in healthy women may be predictable based on the eczema history of their mothers and the level of methylation of a CpG site in the filaggrin ...gene.
Methods Blood samples were collected in first (weeks 8-21) and second (weeks 22-38) halves of pregnancy from the Isle of Wight birth cohort to measure DNA-M using Illumina Infinium Human ...Methylation450 beadchip.
Abstract Background The International Agency for Research on Cancer has concluded that exposure to outdoor fine particles (PM2·5 ) is a risk factor for lung cancer. China is experiencing ...unprecedentedly high levels of PM2·5 air pollution and has the highest lung cancer burden in the world. However, until now, no study has assessed the association between ambient PM2·5 and lung cancer incidence in China. Methods Data of lung cancer incidence between 1990 and 2009 were obtained from the National Cancer Registration of China. The annual concentrations of PM2·5 at 0·1°×0·1° spatial resolution between 1990 and 2005 were estimated by combining remote sensing, global chemical transport models, and ground monitoring air pollution data. A spatial age–period cohort model was used to examine the relative risks (RR) and 95% CI for incident lung cancer associated with increments in 2-year mean PM2·5 concentrations after adjusting for age, period, birth cohort, sex, community type (rural and urban), smoking rate at the community level, as well as the spatial variation in lung cancer incidence. This study was approved by the University of Queensland's behaviour and social sciences ethical review committee (2013000739). Findings During study period, there were 368 762 cases of lung cancer, including 247 533 men and 312 678 cases living in urban areas. The mean concentration of PM2·5 was 69·4 ug/m3 . Incident lung cancer was positively associated with increments in 2-year mean PM2·5 , and the risk was more pronounced in women (RR 1·149, 95% CI 1·120–1·178) than in men (RR 1·055, 95% CI 1·038–1·072; psex interaction <0·0001). The association was smaller in rural areas (RR 1·037, 95% CI 0·998–1·078) than in urban areas (RR 1·060, 95%CI 1·044–1·075; pinteraction =0·03) and stronger in elderly people (>75 years of age; 1·111 95% CI 1·077–1·146) than young people (30–65 years of age; RR 1·074 95% CI 1·052–1·096; pinteraction =0.007). Interpretation In China, lung cancer incidence is associated with PM2·5 air pollution. Effective control measures to reduce levels of air pollution are likely to reduce the incidence of lung cancer in the Chinese population. Further studies are still needed to examine causality of the association between PM2·5 and lung cancer incidence, as this study is an observational epidemiology investigation. This study used community-level incidence and air pollution exposure, but not individual-level information on exposure and outcome. We only had air pollution data for the years 1990 and 2005, and interpolated the data to 1990–2009. These might underestimate the association between air pollution and lung cancer incidence, because random measurement error in exposure will bias the effect estimates towards the null. Funding Hope Run Malathon Fund (Cancer Institute & Hospital, Chinese Academy of Medical Sciences, LC2011Y41), and University of Queensland Research Fellowship (YG).
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