Modeling unobserved heterogeneity in susceptibility to ambient benzoapyrene concentration among children with allergic asthma using a mixture-based clustering approach

Current studies of gene × air pollution interaction typically seek to identify unknown heritability of common complex illnesses arising from variability in the host’s susceptibility to environmental pollutants of interest. Accordingly, a single component generalized linear models are often used to model the risk posed by an environmental exposure variable of interest in relation to a priori determined DNA variants. However, reducing the phenotypic heterogeneity may further optimize such approach, primarily represented by the modeled DNA variants. Here, we reduce phenotypic heterogeneity of asthma severity, and also identify single nucleotide polymorphisms (SNP) associated with phenotype subgroups. Specifically, we first apply an unsupervised learning algorithm method and a non-parametric regression to find a biclustering structure of children according to their allergy and asthma severity. We then identify a set of SNPs most closely correlated with each sub-group. We subsequently fit a logistic regression model for each group against the healthy controls using benzo[a]pyrene (B[a]P) as a representative airborne carcinogen. Application of such approach in a case-control data set shows that SNP clustering may help to partly explain heterogeneity in children’s asthma susceptibility in relation to ambient B[a]P concentration with greater efficiency.Peer ReviewedPostprint (published version

Effect of Polycyclic Aromatic Hydrocarbons Exposure on Cognitive Development in 5 Years Old Children

Objectives: To analyze the impact of polycyclic aromatic hydrocarbons (PAHs) in ambient air at the time of delivery and five years of age on cognitive development in five year old children. Materials and Methods: Two cohorts of children born in the years 2013 and 2014 from Karvina (Northern Moravia, n = 70) and Ceske Budejovice (Southern Bohemia, n = 99) were studied at the age of five years for their cognitive development related to the exposure to PAHs, determined in the ambient air as the concentration of benzo[a]pyrene (B[a]P) and OH–PAH (hydroxy-PAH) metabolites in urine of the newborns at the time of delivery. As psychological tests, the Bender Visual Motor Gestalt Test (BG test) and the Raven Colored Progressive Matrices (RCPM test) were used. Results: Concentrations of B[a]P in the third trimester of mother’s pregnancies were 6.1 ± 4.53 ng/m3 in Karvina, and 1.19 ± 1.28 ng/m3 (p < 0.001) in Ceske Budejovice. Neither the outcome of the RCPM test nor the BG test differed between children in Karvina vs. Ceske Budejovice, or boys vs. girls. Cognitive development in five year old children was affected by the higher exposure to PM2.5 during the third trimester in girls in Karvina. Conclusions: We did not observe any significant effect of prenatal PAH exposure on psychological cognitive tests in five year old children