Purpose: Body mass index (BMI) is associated with asthma but associations of BMI temporal patterns with asthma incidence are unclear. Previous studies suggest that DNA methylation (DNAm) is associated with asthma status and variation in DNAm is a consequence of BMI changes. This study assessed the direct and indirect (via DNAm) effects of BMI trajectories in childhood on asthma incidence at young adulthood. Methods: Data from the Isle of Wight (IoW) birth cohort were included in the analyses. Group-based trajectory modelling was applied to infer latent BMI trajectories from ages 1 to 10 years. An R package, ttscreening, was applied to identify differentially methylated CpGs at age 10 years associated with BMI trajectories, stratified for sex. Logistic regressions were used to further exclude CpGs with DNAm at age 10 years not associated with asthma incidence at 18 years. CpGs discovered via path analyses that mediated the association of BMI trajectories with asthma incidence in the IoW cohort were further tested in an independent cohort, the Avon Longitudinal Study of Children and Parents (ALSPAC). Results: Two BMI trajectories (high vs. normal) were identified. Of the 442,474 CpG sites, DNAm at 159 CpGs in males and 212 in females were potentially associated with BMI trajectories. Assessment of their association with asthma incidence identified 9 CpGs in males and 6 CpGs in females. DNAm at 4 of these 15 CpGs showed statistically significant mediation effects (p-value < 0.05). At two of the 4 CpGs (cg23632109 and cg10817500), DNAm completely mediated the association (i.e., only statistically significant indirect effects were identified). In the ALSPAC cohort, at all four CpGs, the same direction of mediating effects were observed as those found in the IoW cohort, although statistically insignificant. Conclusion: The association of BMI trajectory in childhood with asthma incidence at young adulthood is possibly mediated by DNAm.

DNA methylation (DNAm) patterns over time at 1146 CpGs on coronavirus-related genes were assessed to understand whether the varying differences in susceptibility, symptoms, and the outcomes of the SARS-CoV-2 infection in children and young adults could be explained through epigenetic alterations in a host cell’s transcriptional apparatus to coronaviruses. DNAm data from the Isle of Wight birth cohort (IOWBC) at birth, 10, 18, and 26 years of age were included. Linear mixed models with repeated measurements stratified by sex were used to examine temporal patterns, and cluster analysis was performed to identify CpGs following similar patterns. CpGs on autosomes and sex chromosomes were analyzed separately. The association of identified CpGs and expression of their genes were evaluated. Pathway enrichment analyses of the genes was conducted at FDR = 0.05. DNAm at 635 of the 1146 CpGs on autosomes showed statistically significant time effects (FDR = 0.05). The 635 CpGs were classified into five clusters with each representing a unique temporal pattern of DNAm. Of the 29 CpGs on sex chromosomes, DNAm at seven CpGs in males and eight CpGs in females showed time effects (FDR = 0.05). Sex-specific and non-specific associations of DNAm with gene expression were found at 24 and 93 CpGs, respectively. Genes which mapped the 643 CpGs represent 460 biological processes. We suggest that the observed variability in DNAm with advancing age may partially explain differing susceptibility, disease severity, and mortality of coronavirus infections among different age groups.

The purpose of this study is to examine the associations of neighborhood socioeconomic status, ethnic enclaves, and residential Black segregation with screening for breast, cervical, and colorectal cancers across the state of Texas. Using an ecologic study design, spatial clustering of low breast, cervical and colorectal cancer screening rates were identified across Texas census tracts using local Moran's I statistics. Binomial spatial probit regression was used to estimate the associations between nSES, Hispanic/Latino and Asian American ethnic enclave neighborhoods and residential Black segregation with geospatial clusters of low screening, adjusting for behavioral characteristics. Analysis was conducted in 2024. Of 5,186 tracts, 5.4%, 4.6%, and 8.7% tracts were in low screening clusters for colorectal, cervical, and breast cancer, respectively. Medium and high neighborhood socioeconomic status tracts had reduced odds of being part of low cervical cancer screening clusters. Medium neighborhood socioeconomic status tracts and Hispanic enclave tracts had increased odds of being within a low breast cancer screening cluster. Asian American enclave tracts displayed an increased odds of being in low colorectal cancer and low cervical cancer screening clusters. Tracts with high residential Black segregation demonstrated reduced odds of being in low colorectal cancer and low breast cancer screening clusters. Geospatial clusters of screening uptake are associated with neighborhood socioeconomic status and racial and ethnic neighborhood characteristics. This indicates a need for place-based culturally sensitive interventions to address the specific assets and needs of communities with low screening uptake.

Cox proportional hazard regression analyses for associations of Hispanic enclave status and nSES with OS and EFS.

Demographic and clinical characteristics of children treated for ALL between 2005 and 2017, overall and by treating institutions within the REDIAL Consortium.