Browsing by Subject "Epigenetics"
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(2019)Sleep difficulties have been on the rise for the past decade. Insomnia and sleep difficulties have associations with an increased risk of overall mortality, as well as with a diverse array of complex diseases, such as coronary heart disease, major depressive disorder, fibromyalgia and Alzheimer’s disease. Epigenomics provides information on how environmental factors influence the genome via epigenetic mechanisms, such as DNA methylation. Thus far, epigenome-wide association studies looking at the effects of sleep disturbances on the methylome have provided evidence of distinctive methylation patterns in insufficient sleep, involving biological processes related to neuroplasticity and neurodegeneration. However, more knowledge is needed to determine how the severity of sleeping difficulties influence the methylome. This thesis investigates the effects of increasing sleep difficulties on DNA methylation with an epigenome-wide association study. The study sample is derived from the Health 2000 general population survey. Subjects were divided into three different groups by their self-reported level of sleeping difficulty, and methylation measurements performed from whole blood samples utilizing the Illumina Infinium MethylationEPIC kit, encompassing >850,000 CpG sites. To identify differentially methylated sites, a multivariable regression model was used with age, gender, smoking, alcohol use, cell type distribution and plate and array data as covariates. None of the differentially methylated CpG sites identified remained significant after multiple testing correction. To gain more information regarding which biological processes the methylated sites may be part of, those CpG sites with an uncorrected p-value of <0.0005 were subjected to pathway analysis. Notable significant pathways included oxytocin- and serotonin receptor-mediated signalling pathways and Alzheimer’s disease-amyloid secretase pathway. Altogether, six pathways remained significant after multiple testing correction, with a total of 12 different genes appearing in them. Furthermore, a post-hoc regression analysis was conducted between these 12 genes and their corresponding CpG sites, and health-related quality of life questionnaire responses. Significant results included associations between sleep, and discomfort and symptoms (including pain). As an additional analysis, a database search was conducted to learn more about the genes’ functionality at the level of phenotype. Results included some variant trait associations to sleep, Alzheimer’s disease and cognitive performance. The associations to Alzheimer’s disease and cognitive performance warrant further research with a similar additive model, perhaps with a larger sample.
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(2021)Epigenetics is the study of changes in gene function without affecting the DNA sequence. Epigenetics studies the effects of the environment and behavior on the genome. Researchers have been able to detect several epigenetic modifications such as –DNA methylation, histone acetylation, and microRNA-associated gene silencing. Changes in the epigenome are essential for proper cell function and normal development and can also be induced by environmental factors. Stress is defined as a biological response to physiological and psychological demands which can affect cellular homeostasis. Factors such as prenatal life stress can affect gene function without directly altering the DNA nucleotide sequence. Elevated levels of stress can immobilize with the ability to impair cognitive function. There is evidence that suggests the involvement of epigenetic regulation in disorders such as addiction, depression, schizophrenia, and cognitive dysfunction. Therefore, this systematic review discusses recent findings of the role of epigenetics in prenatal exposure to stress. To achieve this, the thesis will cover different subtopics from genetics, neurobiology, and diseases, neuroscience, biological psychiatry, life sciences, medicine, behavioral brain research, biochemistry & molecular biology, as well as neuroendocrinology. Research questions are 1) Is there an association between epigenetics and prenatal stress? 2) What kind of mechanisms have been found? 3) What kind of techniques have been used in the identification of potential epigenetic mechanisms? What genes are associated with these epigenetic changes?. This study followed the "The Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guideline checklist. Eligibility criteria and search terms where be selected and documented to offer the widest range of articles covering the subjects of this study. A literature search was done using PubMed/Medline, Google scholar, and gray literature. The last sample comprised 59 articles. Data were extracted so that the participants, intervention, comparisons, and outcomes were included. The literature search conducted in this systematic review identified a few findings. First is that the majority of animal and human studies found a significant or moderate association between epigenetics and prenatal stress. Second, DNA methylation is the most studied epigenetic mechanism in maternal exposure to stress Third, genome-wide studies were more common in human studies than in animals and the most widely used method used is Infinium HumanMethylation450 Bead Chip. However, the common methods used in human and animal studies are most likely because of the small sample size and causation cannot be determined. Finally, NR3C1 and FKBP5 genes were the most studied in human studies where they showed the strongest association between prenatal stress and epigenetic modifications. While in animal studies, the most studied genes were Bdnf and Dnmt1 as they showed a significant methylation level after maternal prenatal stress exposure. In conclusion, maternal prenatal stress could trigger epigenetic alterations in neonates in both animals and humans. This holistic review detailed and evaluated locus-specific and studies exploring current knowledge about associations between maternal prenatal stress and epigenetic changes.
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