Genetics and epigenetics of early life development
| Jazyk: | angličtina |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
polygenic and DNA methylation scores
epigenetics breastfeeding aggression prenatal maternal smoking Apgar scores twins genetica early life development agressie tweelingen handedness epigenetica borstvoeding vroege ontwikkeling polygene en DNA-methylatie scores Apgar-scores genetics prenataal roken door de moeder handvoorkeur |
| Popis: | The PhD thesis Genetics and epigenetics of early life development by Veronika Odintsova (VU, Amsterdam) concerns traits and exposures associated with early life development. It contains a series of studies that have as a background the role of nature and nurture in human development. In these studies, the author used contemporary genetic epidemiological methods and the latest molecular biology advances, and applied these to early life traits in two large cohorts in the Netherlands and UK—the Netherlands Twin Register (NTR) and the Avon Longitudinal Study of Parents and Children (ALSPAC). The NTR samples comprises twins, which is a valuable resource in research on early life development and biomarkers, because the twin design allows one evaluate genetic and environmental influences on the phenotypes of interest. Studying early life outcomes and traits, such as a newborn state at birth assessed with Apgar scores (i.e., scores based on newborn appearance, pulse, grimace, activity, and respiration) or handedness, the author found a very small contribution of genetic influences to those traits, and hypothesized that epigenetic modifications could play a role. Most epigenetic programming is thought to take place within the first 1000 days of life. Epigenetic mechanisms are mechanisms that influence gene expression throughout the lifespan. Some epigenetic changes, such as DNA methylation, which are attributable to early life factors and exposures, can persist throughout childhood and into adulthood. This thesis focused on DNA methylation, as a source of variation, in addition to the genetic and environmental sources. It focused, inter alia, on epigenetic differences related to early life exposures – prenatal maternal smoking and breastfeeding – and complex traits – birth weight, BMI, left-handedness, and aggression. The research described in this thesis demonstrates that epigenetic data are a valuable addition to the genetic data, and which can play an important role in improving multi-omics prediction of health outcomes. Whereas DNA-based predictors are static and solely capture genomic information, epigenetic biomarkers are dynamic, and may capture both genetic and environmental information. The research in this thesis identified several promising new epigenetic signatures related to breastfeeding and handedness. Furthermore, it showed that epigenetic data summarized in epigenetic scores explained more variance in prenatal maternal smoking, current smoking, and in BMI than polygenic scores. Finally, this work identified novel methodologies associated with epigenetic and twin data in population-based and biomarker studies, and offered guidance on establishing a research twin register. The findings in this thesis contribute to the developing field of personalized medicine and epigenomics. |
| Databáze: | OpenAIRE |
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