Biology subjects

Osborne, A. J.

Publications and source records attributed to Osborne, A. J..

5 recordsLinked to original sources

bioRxiv2021

Hypomethylation in FASTKD1 detected in the association between in utero tobacco exposure and conduct problem in a New Zealand longitudinal study

Despite the known adverse effects of in utero tobacco exposure on offspring health, maternal tobacco use during pregnancy remains prevalent and is a major driver of health inequalities. One such health inequality is the development of conduct problem (CP) in exposed offspring which may be mediated by methylation changes that persist into adulthood. Here we apply a genome-wide approach to probe the association between maternal tobacco use during pregnancy and CP outcomes in exposed offspring. We examined maternal tobacco use during pregnancy (in utero exposure) in the Christchurch Health and Development Study, a longitudinal birth cohort studied for over 40 years. We then evaluated the interaction between methylation effects of in utero exposure and CP score. When modelling this interaction between in utero exposure and CP score we detected nominal DNA methylation differences, at FASTKD1 which has roles in early development. Our observations are consistent with DNA methylation mediating the development of CP following in utero tobacco exposure. In addition, we detected nominal significance in FRMDA4 and MYO1G between individuals exposed to tobacco in utero and those that were unexposed, however these did not reach significance after adjustment for multiple testing. However due to limited power in our analysis, further studies are needed to investigate the interaction between in utero tobacco exposure and high CP health outcomes.

genomics↗

bioRxiv2020

Epigenetic signatures associated with the observed link between maternal tobacco use during pregnancy, and offspring conduct problems in childhood and adolescence

Maternal tobacco smoking during pregnancy is a large driver of health inequalities and a higher prevalence of conduct problem has been observed in exposed offspring. Further, maternal tobacco use during pregnancy can also alter offspring DNA methylation. However, currently, limited molecular evidence have been found to support this observation. Thus we aim to examine the association between maternal tobacco use in pregnancy and whether offspring Conduct problems is mediated by tobacco exposure-induced via DNA methylation differences. Understanding the etiology of the causal link will be crucial in the early identification and treatment of CP in children and adolescents. DNA was sourced from the Christchurch Health and Development Study, a longitudinal birth cohort studied for over 40 years in New Zealand. Bisulfite-based amplicon sequencing of 10 loci known to play a role in neurodevelopment, or with associations with CP phenotypes, was undertaken. We identified nominally significant differential DNA methylation at specific CpG sites in CYP1A1, ASH2L and MEF2C in individuals with Conduct problems who were exposed to tobacco in utero. We conclude that environmentally-induced DNA methylation differences could play a role in the observed link between maternal tobacco use during pregnancy and childhood/adolescent Conduct problems However, larger sample sizes are needed to produce an adequate amount of power to investigate this interaction further.

genomics↗

bioRxiv2020

A validation of Illumina EPIC array system with bisulfite-based amplicon sequencing

The Illumina Infinium(R) MethylationEPIC BeadChip system (hereafter EPIC array) is considered to be the current gold standard detection method for assessing DNA methylation at the genome-wide level. EPIC arrays are used for hypothesis generation or pilot studies, the natural conclusion is to validate methylation candidates and expand these in a larger cohort, in a targeted manner. As such, an accurate smaller-scale, targeted technique, that generates data at the individual CpG level that is equivalent to the EPIC array, is needed. Here, we tested an alternative DNA methylation detection technique, known as bisulfite-based amplicon sequencing (BSAS), to determine its ability to validate CpG sites detected in EPIC array studies. BSAS was able to detect differential DNA methylation at CpG sites to a degree which correlates highly with the EPIC array system. However, BSAS correlated less well with EPIC array data when the magnitude of change via EPIC array was greater than 5%, suggesting that this lower specificity at larger differential methylation values is a consequence of PCR amplification that BSAS requires. However, our data suggests that BSAS does offer advantages that the EPIC array: BSAS amplifies a region of the genome (~500bp) around a CpG of interest, allowing analyses of other CpGs in the region that may not be present on the EPIC array, aiding discovery of novel CpG sites and differentially methylated regions of interest. We conclude that BSAS offers a valid investigative tool for specific regions of the genome that are currently not contained on the array system.

genomics↗

bioRxiv2019

Genome-wide DNA methylation analysis of heavy cannabis use in a New Zealand longitudinal cohort

Cannabis use is of increasing public health interest globally. Here we examined the effect of cannabis use, with and without tobacco, on genome-wide DNA methylation in a longitudinal birth cohort (Christchurch Health and Development Study). We found the most differentially methylated sites in cannabis with tobacco users were in the AHRR and F2RL3 genes, replicating previous studies on the effects of tobacco. Cannabis-only users had no evidence of differential methylation in these genes, or at any other loci at the epigenomewide significance level (P<10-7). However, there were 521 sites differentially methylated at P<0.001 which were enriched for genes involved in cardiomyopathy and neuronal signalling. Further, the most differentially methylated loci were associated with genes with reported roles in brain function (e.g. TMEM190, MUC3L, CDC20 and SP9). We conclude that the effects of cannabis use on the mature human blood methylome differ from, and are less pronounced than, the effects of tobacco use, and that larger sample sizes are required to investigate this further.

genomics↗

bioRxiv2017

A ‘phenotypic hangover’ – the predictive adaptive response and multigenerational effects of altered nutrition on the transcriptome of Drosophila melanogaster

The Developmental Origins of Health and Disease (DOHaD) hypothesis predicts that early-life environmental exposures can be detrimental to later-life health, and that mismatch between the pre- and postnatal environment may contribute to the growing non-communicable disease (NCD) epidemic. Within this is an increasingly recognised role for epigenetic mechanisms; epigenetic modifications can be influenced by, e.g., nutrition, and can alter gene expression in mothers and offspring. Currently, there are no whole-genome transcriptional studies of response to nutritional alteration. Thus, we sought to explore how nutrition affects the expression of genes involved in epigenetic processes in Drosophila melanogaster. We manipulated Drosophila food macronutrient composition at the F0 generation, mismatched F1 offspring back to a standard diet, and analysed the transcriptome of the F0 - F3 generations by RNA-sequencing. At F0, the altered (high protein, low carbohydrate, HPLC) diet increased expression of genes involved in epigenetic processes, with coordinated downregulation of genes involved in immunity, neurotransmission and neurodevelopment, oxidative stress and metabolism. Upon reversion to standard nutrition, mismatched F1 and F2 generations displayed multigenerational inheritance of altered gene expression. By the F3 generation, gene expression had reverted to F0 (matched) levels. These nutritionally-induced gene expression changes demonstrate that dietary alteration can upregulate epigenetic genes, which may influence the expression of genes with broad biological functions. Further, the multigenerational inheritance of the gene expression changes in F1 and F2 mismatched generations suggests a predictive adaptive response (PAR) to maternal nutrition. Our findings may help to understand the interaction between maternal diet and future offspring health, and have direct implications for the current NCD epidemic.

genomics↗