ORCID Profile
0000-0002-3515-0557
Current Organisations
Deakin University
,
Murdoch Childrens Research Institute
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Publisher: Springer Science and Business Media LLC
Date: 25-09-2023
Publisher: Bentham Science Publishers Ltd.
Date: 05-2021
DOI: 10.2174/1567205018666210823100721
Abstract: There is strong evidence that epigenetic age acceleration is associated with increased risk of later-life diseases and all-cause mortality. However, there is currently limited evidence that suggests accelerated epigenetic age is associated with dementia risk. This study aims to clarify whether epigenetic biomarkers of accelerated aging can predict dementia risk, which is an important consideration as aging is the greatest risk factor for the disease. DNA methylation was measured in peripheral blood s les provided by 160 participants from the ASPirin in Reducing Events in the Elderly study, including 73 pre-symptomatic dementia cases and 87 controls matched for age, sex, and smoking and education status. Epigenetic age was calculated using Horvath, Hannum, GrimAge and PhenoAge DNA methylation clocks, and age acceleration (the disparity between chronological age and epigenetic age) was determined. There was no difference in age acceleration between dementia cases and controls. In males, only Hannum’s intrinsic epigenetic age acceleration was increased in pre-symptomatic dementia cases compared to controls (Δ +1.8 years, p = 0.03). These findings provide no strong evidence that accelerated epigenetic aging measured in peripheral blood can predict dementia risk.
Publisher: MDPI AG
Date: 06-04-2018
DOI: 10.3390/NU10040455
Publisher: Future Medicine Ltd
Date: 12-2020
Abstract: Aim: To investigate whether genes implicated in dementia pathogenesis are differently methylated in peripheral blood. Materials & methods: Participants included 160 cognitively healthy in iduals aged 70+ years: 73 who were subsequently diagnosed with dementia and 87 controls matched on age, gender, education, smoking and baseline cognition. A total of 49 participants also provided blood s les at diagnosis. Blood DNA methylation of APOE, APP, BDNF, PIN1, SNCA and TOMM40 was examined. Results: A total of 56 of 299 probes were differentially methylated in dementia compared with controls and 39 probes prior to diagnosis. The greatest effect size was in APP (cg19423170, Δ-8.32%, adjusted p = 0.009 at diagnosis cg19933173, Δ-4.18%, adjusted p 0.0001 prediagnosis). Conclusion: Genes implicated in dementia pathogenesis show differential blood methylation in dementia, even prior to diagnosis.
Publisher: Future Medicine Ltd
Date: 03-2017
Abstract: There is considerable interest in the potential nongenetic transmission of a suite of mental health conditions across generations, with epigenetics emerging as a candidate mediator of such effects. This review summarizes findings from 22 studies measuring candidate gene DNA methylation and seven epigenome-wide association studies of offspring epigenetic profile in women with adverse mental wellbeing measures (stress, depression or anxiety) in pregnancy. Despite some compelling evidence to suggest an association, there is a lack of reproducible findings, potentially linked to a number of limitations to this research and the field more broadly. Large cohorts with well characterized exposures across pregnancy are now needed. There is exciting potential that epigenetics may help explain some of the link between maternal wellbeing and child health outcomes, thereby informing novel interventions, but future studies must address current limitations to advance translational knowledge in this area.
Publisher: Future Medicine Ltd
Date: 31-10-2023
Publisher: Wiley
Date: 07-09-2019
DOI: 10.1016/J.JALZ.2019.05.011
Abstract: In iduals with homozygosity for the apolipoprotein E (APOE) ε4 allele are in the highest risk category for late-onset Alzheimer's disease (LOAD). However, some in iduals in this category do not develop LOAD beyond the age of 75 years, despite being at elevated genetic risk. These "resilient" in iduals may carry protective genetic factors. This study aimed to systematically review any previous studies that involved resilient APOE ε4 homozygotes and to identify possible modifying or protective genetic factors. Fifteen studies met our inclusion criteria and reported genetic factors contributing to reduced risk. We found that only two single nucleotide polymorphisms, CASP7 rs10553596 and SERPINA3 rs4934-A/A, had strong evidence. We found a paucity of studies adequately designed to discover protective genetic factors against LOAD. Many studies combined APOE ε4 homozygotes and heterozygotes together because of small s le sizes and used control populations too young to be clearly defined as controls for LOAD.
Publisher: Springer Science and Business Media LLC
Date: 11-04-2019
Publisher: Frontiers Media SA
Date: 19-06-2018
Publisher: Wiley
Date: 2020
DOI: 10.1002/DAD2.12056
Publisher: Oxford University Press (OUP)
Date: 17-04-2019
Abstract: DNA methylation (DNAm) algorithms of biological age provide a robust estimate of an in idual’s chronological age and can predict their risk of age-related disease and mortality. This study reviewed the evidence that environmental, lifestyle and health factors are associated with the Horvath and Hannum epigenetic clocks. A systematic search identified 61 studies. Chronological age was correlated with DNAm age in blood (median .83, range .13–.99). In a meta-analysis body mass index (BMI) was associated with increased DNAm age (Hannum β: 0.07, 95% CI 0.04 to 0.10 Horvath β: 0.06, 95% CI 0.02 to 0.10), but there was no association with smoking (Hannum β: 0.12, 95% CI −0.50 to 0.73 Horvath β:0.18, 95% CI −0.10 to 0.46). DNAm age was positively associated with frailty (three studies, n = 3,093), and education was negatively associated with the Hannum estimate of DNAm age specifically (four studies, n = 13,955). For most other exposures, findings were too inconsistent to draw conclusions. In conclusion, BMI was positively associated with biological aging measured using DNAm, with some evidence that frailty also increased aging. More research is needed to provide conclusive evidence regarding other exposures. This field of research has the potential to provide further insights into how to promote slower biological aging and ultimately prolong healthy life.
Publisher: Wiley
Date: 10-02-2022
DOI: 10.1002/SMI.3131
Abstract: Maternal stress during pregnancy is associated with differential DNA methylation in offspring and disrupted cortisol secretion. This study aimed to determine methylation signatures of cortisol levels in children, and whether associations differ based on maternal post‐traumatic stress disorder (PTSD). Blood epigenome‐wide methylation and fasting cortisol levels were measured in 118 offspring of mothers recruited from the Kosovo Rehabilitation Centre for Torture Victims. Mothers underwent clinically administered assessment for PTSD using Diagnostic and Statistical Manual of Mental Disorders. Correlations between offspring methylation and cortisol levels were examined using epigenome‐wide analysis, adjusting for covariates. Subsequent analysis focussed on a priori selected genes involved in the hypothalamic–pituitary–adrenal (HPA) axis stress signalling. Methylation at four sites were correlated with cortisol levels (cg15321696, r = −0.33, cg18105800, r = +0.33, cg00986889, r = −0.25, and cg15920527, r = −0.27). In adjusted multivariable regression, when stratifying based on prenatal PTSD status, significant associations were only found for children born to mothers with prenatal PTSD ( p 0.001). Several sites within HPA axis genes were also associated with cortisol levels in the maternal PTSD group specifically. There is evidence that methylation is associated with cortisol levels, particularly in offspring born to mothers with prenatal PTSD. However, larger studies need to be carried out to independently validate these findings.
Publisher: Informa UK Limited
Date: 27-04-2017
Publisher: Wiley
Date: 08-11-2017
Publisher: Future Medicine Ltd
Date: 06-2021
Abstract: Aim: To investigate the association between maternal post-traumatic stress disorder (PTSD) during pregnancy and offspring DNA methylation and cortisol levels. Materials & methods: Blood genome-wide DNA methylation and cortisol was measured in the youngest child of 117 women who experienced sexual violence/torture during the Kosovo war. Results: Seventy-two percent of women had PTSD symptoms during pregnancy. Their children had higher cortisol levels and differential methylation at candidate genes ( NR3C1, HTR3A and BNDF) . No methylation differences reached epigenome-wide corrected significance levels. Conclusion: Identifying the biological processes whereby the negative effects of trauma are passed across generations and defining groups at high risk is a key step to breaking the intergenerational transmission of the effects of mental disorders.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.CLINBIOCHEM.2018.05.020
Abstract: As the prevalence of Alzheimer's disease (AD) increases, the search for a definitive, easy to access diagnostic biomarker has become increasingly important. Micro RNA (miRNA), involved in the epigenetic regulation of protein synthesis, is a biological mark which varies in association with a number of disease states, possibly including AD. Here we comprehensively review methods and findings from 26 studies comparing the measurement of miRNA in blood between AD cases and controls. Thirteen of these studies used receiver operator characteristic (ROC) analysis to determine the diagnostic accuracy of identified miRNA to predict AD, and three studies did this with a machine learning approach. Of 8098 in idually measured miRNAs, 23 that were differentially expressed between AD cases and controls were found to be significant in two or more studies. Only six of these were consistent in their direction of expression between studies (miR-107, miR-125b, miR-146a, miR-181c, miR-29b, and miR-342), and they were all shown to be down regulated in in iduals with AD compared to controls. Of these directionally concordant miRNAs, the strongest evidence was for miR-107 which has also been shown in previous studies to be involved in the dysregulation of proteins involved in aspects of AD pathology, as well as being consistently downregulated in studies of AD brains. We conclude that imperative to the discovery of reliable and replicable miRNA biomarkers of AD, standardised methods of measurements, appropriate statistical analysis, utilization of large datasets with machine learning approaches, and comprehensive reporting of findings is urgently needed.
Publisher: Informa UK Limited
Date: 22-07-2019
DOI: 10.1080/10408363.2019.1639129
Abstract: Dementia is an overarching term which describes a group of symptoms that result in long-term decline in cognitive functioning that is significant enough to affect daily function. It is caused by a number of different diseases, the most common of which is Alzheimer's disease. Currently, there are no definitive biomarkers for preclinical or diagnostic use, or which differentiate between underlying disease types. The purpose of this review is to highlight several important areas of research on blood-based biomarkers of dementia, with a specific focus on epigenetic biomarkers. A systematic search of the literature identified 77 studies that compared blood DNA methylation between in iduals with dementia and controls and 45 studies that measured microRNA. Very few studies were identified that focused on histone modifications. There were many promising findings from studies in the field of blood-based epigenetic biomarkers of dementia, however, a lack of consistency in study design, technologies, and platforms used for the biomarker measurement, as well as statistical analysis methods, have h ered progress. To date, there are very few findings that have been independently replicated across more than one study, indicating a preponderance of false-positive findings and the field has likely been plagued by positive publication bias. Here, we highlight and discuss several of the limitations of existing studies and provide recommendations for how these could be overcome in future research. A robust framework should be followed to enable development of the most valid and reproducible biomarkers with the strongest clinical utility. Defining a series of biomarkers that may be complimentary to each other could permit a stronger multifactorial biomarker to be developed that would allow for not only accurate dementia diagnosis but preclinical detection.
Publisher: Oxford University Press (OUP)
Date: 12-2016
DOI: 10.1093/EEP/DVW023
Publisher: Frontiers Media SA
Date: 09-04-2019
No related grants have been discovered for Peter Fransquet.