RESUMO
Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (PFDR = 6.92 × 10-8) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (PFDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.
Assuntos
Metilação de DNA , Idade Materna , Metilação de DNA/genética , Humanos , Feminino , Recém-Nascido , Criança , Adulto , Masculino , Pré-Escolar , Ilhas de CpG/genética , GravidezRESUMO
Agricultural intensification is a well-known driver of biodiversity loss. Crop diversity and its changes over space and time drive land use intensity and impact biodiversity of agricultural landscapes, while meeting the growing demand for human food and nutrition resources. Loss of biodiversity in agricultural landscapes reduces primary productivity and soil health and erodes a range of other ecosystem services. At present, while having partial understanding of many processes, we lack a general synthesis of our knowledge of the links between crop diversity and biodiversity. We will therefore conduct a systematic review by searching multiple agriculture, ecology and environmental science databases (e.g. Web of Science, Geobase, Agris, AGRICOLA, GreenFILE) to identify studies reporting the impacts of crop diversity and crop type on the biological diversity of fauna and flora in agricultural landscapes. Response variables will include metrics of species richness, abundance, assemblage, community composition and species rarity. Screening, data coding and data extraction will be carried out by one researcher and a subset will be independently carried out by a second researcher for quality control. Study quality and risk of bias will be assessed. Evidence will first be mapped to species/taxa then assessed for further narrative or statistical synthesis based on comparability of results and likely robustness. Gaps in the evidence base will also be identified with a view toward future research and policy directions for nutrition, food systems and ecology.