Identifying intergenerational patterns of correlated methylation sites

Mou, Xichen; Zhang, Hongmei; Arshad, S.H.

doi:10.1214/21-aoas1511

Cited by 2 publications

(3 citation statements)

References 28 publications

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“…Other epigenetic factors may also be passed in sperm, such as non‐coding RNAs and retained histones. 12 Recent epidemiological studies based on probabilistic models examined and supported intergenerational epigenetic inheritance, 13 , 14 where it was shown that at some CpG sites, the association of DNA methylation between mothers and offspring was stronger compared to the association between fathers and offspring. The number of CpGs with fathers being dominant in DNA methylation transmission is much smaller.…”

Section: Epigenetic Transfer Of Informationmentioning

confidence: 99%

“… 61 Data analyses in transgenerational epigenetic research mainly focus on DNA methylation transmission from one generation to the next and transgenerational association studies. 13 , 14 , 67 , 68 Further development of multiple‐exposure, multiple‐mediator and multiple‐outcome framework in studies of multi‐generational epigenetic inheritance is needed.…”

Section: Data Analysis In Epigenetic Research and Critical Review Of ...mentioning

confidence: 99%

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The role of epigenetics in multi‐generational transmission of asthma: An NIAID workshop report‐based narrative review

Wheatley

Holloway

Svanes

et al. 2022

Clin Experimental Allergy

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There is mounting evidence that environmental exposures can result in effects on health that can be transmitted across generations, without the need for a direct exposure to the original factor, for example, the effect of grandparental smoking on grandchildren. Hence, an individual's health should be investigated with the knowledge of cross‐generational influences. Epigenetic factors are molecular factors or processes that regulate genome activity and may impact cross‐generational effects. Epigenetic transgenerational inheritance has been demonstrated in plants and animals, but the presence and extent of this process in humans are currently being investigated. Experimental data in animals support transmission of asthma risk across generations from a single exposure to the deleterious factor and suggest that the nature of this transmission is in part due to changes in DNA methylation, the most studied epigenetic process. The association of father's prepuberty exposure with offspring risk of asthma and lung function deficit may also be mediated by epigenetic processes. Multi‐generational birth cohorts are ideal to investigate the presence and impact of transfer of disease susceptibility across generations and underlying mechanisms. However, multi‐generational studies require recruitment and assessment of participants over several decades. Investigation of adult multi‐generation cohorts is less resource intensive but run the risk of recall bias. Statistical analysis is challenging given varying degrees of longitudinal and hierarchical data but path analyses, structural equation modelling and multilevel modelling can be employed, and directed networks addressing longitudinal effects deserve exploration as an effort to study causal pathways.

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Section: Epigenetic Transfer Of Informationmentioning

confidence: 99%

Section: Data Analysis In Epigenetic Research and Critical Review Of ...mentioning

confidence: 99%

The role of epigenetics in multi‐generational transmission of asthma: An NIAID workshop report‐based narrative review

Wheatley

Holloway

Svanes

et al. 2022

Clin Experimental Allergy

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“…Generalized beta distribution fits the definition of DNAm defined as beta values, and in addition, accounts for the correlation structures among adjacent CpG sites. It has been used to model the distribution of nominal family income and stock indexes in economics [ 21 ] and to identify the intergenerational patterns of DNAm levels [ 22 ] in the epigenetic study.…”

Section: Introductionmentioning

confidence: 99%

Gbdmr: identifying differentially methylated CpG regions in the human genome via generalized beta regressions

Wu,

Mou,

Zhang

2024

BMC Bioinformatics

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Background DNA methylation is a biochemical process in which a methyl group is added to the cytosine-phosphate-guanine (CpG) site on DNA molecules without altering the DNA sequence. Multiple CpG sites in a certain genome region can be differentially methylated across phenotypes. Identifying these differentially methylated CpG regions (DMRs) associated with the phenotypes contributes to disease prediction and precision medicine development. Results We propose a novel DMR detection algorithm, gbdmr. In contrast to existing methods under a linear regression framework, gbdmr assumes that DNA methylation levels follow a generalized beta distribution. We compare gbdmr to alternative approaches via simulations and real data analyses, including dmrff, a new DMR detection approach that shows promising performance among competitors, and the traditional EWAS that focuses on single CpG sites. Our simulations demonstrate that gbdmr is superior to the other two when the correlation between neighboring CpG sites is strong, while dmrff shows a higher power when the correlation is weak. We provide an explanation of these phenomena from a theoretical perspective. We further applied the three methods to multiple real DNA methylation datasets. One is from a birth cohort study undertaken on the Isle of Wight, United Kingdom, and the other two are from the Gene Expression Omnibus database repository. Overall, gbdmr identifies more DMR CpGs linked to phenotypes than dmrff, and the simulated results support the findings. Conclusions Gbdmr is an innovative method for detecting DMRs based on generalized beta regression. It demonstrated notable advantages over dmrff and traditional EWAS, particularly when adjacent CpGs exhibited moderate to strong correlations. Our real data analyses and simulated findings highlight the reliability of gbdmr as a robust DMR detection tool. The gbdmr approach is accessible and implemented by R on GitHub: https://github.com/chengzhouwu/gbdmr.

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Identifying intergenerational patterns of correlated methylation sites

Cited by 2 publications

References 28 publications

The role of epigenetics in multi‐generational transmission of asthma: An NIAID workshop report‐based narrative review

The role of epigenetics in multi‐generational transmission of asthma: An NIAID workshop report‐based narrative review

Gbdmr: identifying differentially methylated CpG regions in the human genome via generalized beta regressions

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