Epigenetics, heritability and longitudinal analysis
MetadataShow full item record
© 2018 The Author(s). Background: Longitudinal data and repeated measurements in epigenome-wide association studies (EWAS) provide a rich resource for understanding epigenetics. We summarize 7 analytical approaches to the GAW20 data sets that addressed challenges and potential applications of phenotypic and epigenetic data. All contributions used the GAW20 real data set and employed either linear mixed effect (LME) models or marginal models through generalized estimating equations (GEE). These contributions were subdivided into 3 categories: (a) quality control (QC) methods for DNA methylation data; (b) heritability estimates pretreatment and posttreatment with fenofibrate; and (c) impact of drug response pretreatment and posttreatment with fenofibrate on DNA methylation and blood lipids. Results: Two contributions addressed QC and identified large statistical differences with pretreatment and posttreatment DNA methylation, possibly a result of batch effects. Two contributions compared epigenome-wide heritability estimates pretreatment and posttreatment, with one employing a Bayesian LME and the other using a variance-component LME. Density curves comparing these studies indicated these heritability estimates were similar. Another contribution used a variance-component LME to depict the proportion of heritability resulting from a genetic and shared environment. By including environmental exposures as random effects, the authors found heritability estimates became more stable but not significantly different. Two contributions investigated treatment response. One estimated drug-associated methylation effects on triglyceride levels as the response, and identified 11 significant cytosine-phosphate-guanine (CpG) sites with or without adjusting for high-density lipoprotein. The second contribution performed weighted gene coexpression network analysis and identified 6 significant modules of at least 30 CpG sites, including 3 modules with topological differences pretreatment and posttreatment. Conclusions: Four conclusions from this GAW20 working group are: (a) QC measures are an important consideration for EWAS studies that are investigating multiple time points or repeated measurements; (b) application of heritability estimates between time points for individual CpG sites is a useful QC measure for DNA methylation studies; (c) drug intervention demonstrated strong epigenome-wide DNA methylation patterns across the 2 time points; and (d) new statistical methods are required to account for the environmental contributions of DNA methylation across time. These contributions demonstrate numerous opportunities exist for the analysis of longitudinal data in future epigenetic studies.
Showing items related by title, author, creator and subject.
Patterns of DNA methylation across the leptin core promoter in four diverse Asian and north American populationsMosher, M.; Melton, Phillip; Stapleton, P.; Schanfield, M.; Crawford, M. (2017)© 2017 Wayne State University Press. DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments of methyl groups along the DNA that are capable ...
Zahir, Aishath Zehereen (2008)E-glass has been widely used as a reinforcing material for years, especially as a plastic reinforcer in the production of GRP (Glass Reinforced Plastic). Failure of GRP materials under stress came in to the picture quite ...
Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the pregnancy and childhood epigenetics (PACE) consortiumSharp, G.; Salas, L.; Monnereau, C.; Allard, C.; Yousefi, P.; Everson, T.; Bohlin, J.; Xu, Z.; Huang, R.; Reese, S.; Xu, C.; Baïz, N.; Hoyo, C.; Agha, G.; Roy, R.; Holloway, J.; Ghantous, A.; Merid, S.; Bakulski, K.; Küpers, L.; Zhang, H.; Richmond, R.; Page, C.; Duijts, L.; Lie, R.; Melton, Phillip; Vonk, J.; Nohr, E.; Williams-DeVane, C.; Huen, K.; Rifas-Shiman, S.; Ruiz-Arenas, C.; Gonseth, S.; Rezwan, F.; Herceg, Z.; Ekström, S.; Croen, L.; Falahi, F.; Perron, P.; Karagas, M.; Quraishi, B.; Suderman, M.; Magnus, M.; Jaddoe, V.; Taylor, J.; Anderson, D.; Zhao, S.; Smit, H.; Josey, M.; Bradman, A.; Baccarelli, A.; Bustamante, M.; Håberg, S.; Pershagen, G.; Hertz-Picciotto, I.; Newschaffer, C.; Corpeleijn, E.; Bouchard, L.; Lawlor, D.; Maguire, R.; Barcellos, L.; Smith, G.; Eskenazi, B.; Karmaus, W.; Marsit, C. (2017)© The Author 2017. Published by Oxford University Press. All rights reserved. Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that ...