Epigenome-wide change and variation in DNA methylation in childhood: Trajectories from birth to late adolescence

DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5019 blood samples collected at multiple time-points from birth to late adolescence from 2348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for nonlinear change and inter-individual variation in nonlinear trajectories was somewhat less common (11% and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. By contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often nonlinear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu.ac.uk.

Full Analysis of Lung Cancer Mortality/Radon Relationship with Simple Nonlinear Concepts

We analyze the relationship between the lung cancer mortality and the indoor radon intensity from the viewpoint of nonlinear mathematics. We conclude that their relationship is governed by the proportionality law where the cumulative lung cancer mortality Y is negatively proportional to the cumulative radon intensity X; or specifically, the nonlinear change of nonlinear face value (qYu – qY) is negatively proportional to the nonlinear change of nonlinear face value (X – Xb). The author obtained a set of data from late Professor Cohen on the lung-cancer mortality rate versus indoor radon level collected from 1,597 counties and territory of the USA. We initially presented the data as various primitive elementary graphs; then extended them to the primary graphs, leading graphs, and the proportionality graphs. The article emphasizes the building of a straight-line proportionality relationship for the dose-response data in a log-linear and/or log-log graphs. It demonstrates a straightforward methodology for solving the key upper asymptotes (Yu) for the proportionality equation using the Microsoft Excel via determining the “coefficient of determination”. (Note: q = log, Yu = upper asymptote of Y, Xb = bottom asymptote of X)

Reconversion and Retrieval: Nonlinear Change in African Catholic Practice

Against models of conversion that presume a trajectory or a progression from one religion to another, this article proposes a less linear, more complex, and ultimately more empirical understanding of religious change in Africa. It does so by foregrounding the particularities of Roman Catholicism—its privileging of materiality and practice, and of community and tradition. In the course of so doing, this article explores the overlaps between modernist thinking, Protestant ideals, and teleological trajectories; the factors behind reconversion and religious oscillation in sub-Saharan African contexts; inculturation and other continuity paradigms in Catholicism; the significance of the Renaissance for early modern Catholic missions; and the ministry of a contemporary Italian Catholic missionary serving in northern Mozambique. This article proposes that Catholic history and Catholic assumptions offer valuable resources for thinking beyond and thinking against linear models of religious conversion.

Epigenome-wide change and variation in DNA methylation from birth to late adolescence

DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5,019 blood samples collected at multiple time-points from birth to late adolescence from 2,348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for nonlinear change and inter-individual variation in nonlinear trajectories was somewhat less common (11% and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. By contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often nonlinear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu.ac.uk.