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Environmental Health PHGKB

Specific PHGKB|Environmental Health PHGKB|PHGKB

Last Posted: Jan 31, 2023
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Molecular mechanisms of environmental exposures and human disease
H Wu et al, Nature Rev Genetics, January 30, 2023

We review evidence showing the environmental impact on gene expression through epigenetic modifications, including DNA methylation, histone modification and non-coding RNAs. We also highlight recent studies that evaluate recently discovered molecular processes through which the environment can exert its effects, including extracellular vesicles, the epitranscriptome and the mitochondrial genome. Finally, we discuss current challenges when studying the exposome — the cumulative measure of environmental influences over the lifespan — and its integration into future environmental health research.

Diet modulates genetic effects on longevity.
et al. Nature genetics 2023 1

Why some individuals live longer than others is of major interest across a range of scientific disciplines, from evolutionary biology to human health. Evolutionary theory tells us that lifespan-reducing alleles should be purged from the gene pool1, yet decades of genome-wide association studies (GWAS) and model organism studies have shown that such alleles persist. Here, we address one potential explanation for this conundrum, the idea that alleles that regulate lifespan do so only in certain contexts (known as ‘genotype-by-environment’ (GxE) effects).

A DNA methylation atlas of normal human cell types
N Loyfer et al, Nature, January 4, 2023

We describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39?cell types sorted from 205?healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development.

Improved two-step testing of genome-wide gene–environment interactions
ES Kawagushi et al, Genetic Epidemiology, December 26, 2022

We introduce a new significance-based allocation into bins for Step-2 testing that overcomes the displacement issue and propose a computationally efficient approach to account for multiple testing within bins. Simulation results demonstrate that these simple improvements can provide substantially greater power than current methods under several scenarios. An application to a multistudy collaboration for understanding colorectal cancer reveals a G?×?Sex interaction located near the SMAD7 gene.

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