Identifying heterogeneous transgenerational DNA methylation sites via clustering in beta regression

Han, Shengtong; Zhang, Hongmei; Lockett, Gabrielle A.; Mukherjee, Nandini; Holloway, John W.; Karmaus, Wilfried

doi:10.1214/15-aoas865

Cited by 6 publications

(10 citation statements)

References 29 publications

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“…When comparing the findings from the proposed method and the results of HAN (Han et al (2015)), patterns of clusters 4 and 5 are consistent with the patterns of clusters 6 and 4 in the Table 7 from Han's work, which indicates that transmission patterns of these two clusters are insensitive overall with respect to the use of blocks. More importantly, it is interesting to see that a much larger number of CpGs showing paternal-predominance in DNA methylation transmission are identified, using the proposed method, especially when we use approach two to determine dependent blocks.…”

Section: Real Data Analysissupporting

confidence: 78%

“…We use results from block-determination approach two (the less restrictive approach) to illustrate the differences. In Table 8 from Han et al (2015), 53 CpGs were identified as paternal-predominated transmission sites. Our approach identified three clusters (clusters 1 to 3; Table 5) with in total 794 out of 4063 CpG sites (around 15 times as in Han's work) such that DNA methylation transmission at those CpGs was mainly from paternal transmission and each cluster showed different levels of dominance with cluster 1 demonstrating the strongest paternal predominance and cluster 3 the weakest.…”

Section: Real Data Analysismentioning

confidence: 99%

“…Some effort has contributed to understanding DNA methylation transmission patterns. For instance, the methods developed by Han et al (2015), referred to as HAN for the rest of the article, is based on a beta regression to examine DNA methylation inheritance heterogeneity at different CpG sites between mothers, fathers, and their offspring. HAN grouped CpG sites based on beta regression coefficients.…”

Section: Introductionmentioning

confidence: 99%

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Identifying intergenerational patterns of correlated methylation sites

2022

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DNA methylation can be transmitted through generations. This paper proposes a clustering method to identify the intergenerational patterns from parents to their offspring. Motivated by the potential of correlation between DNA methylation sites, we use the multivariate generalized beta distribution to model the blockwise correlation structure among the sites. A stochastic EM algorithm is implemented to estimate the parameters, and BIC is applied to determine the optimal number of clusters. Simulations demonstrate the feasibility of the proposed method. We further applied the approach to cluster DNA methylation data generated from a cohort study on asthma and allergic conditions.

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Section: Real Data Analysissupporting

confidence: 78%

Section: Real Data Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identifying intergenerational patterns of correlated methylation sites

2022

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“…The linear mixed model is more flexible in adjusting for covariates, accounting different types of study designs, and explicity addressing environmental variation (123, 126). In addition to studying epigenetic inheritance at level of individual CpGs, transgenerational inheritance can also be evaluated for groups of CpGs that share similar pattern of DNAm transmission (127). This approach, which incorporates unsupervised cluster into beta regression, was recently developed by Han et al (127), and was able to identify sets of CpGs that have same/different inheritance patterns between mother-offspring and father-offspring.…”

Section: Epigenetic Transmission Across Generations In Allergic Diseasementioning

confidence: 99%

Transgenerational and intergenerational epigenetic inheritance in allergic diseases

Knudsen

Rezwan

Jiang

et al. 2018

Journal of Allergy and Clinical Immunology

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It has become clear that early life (including in utero exposures) is a key window of vulnerability during which environmental exposures can alter developmental trajectories and initiate allergic disease development. However, recent evidence suggests that there might be additional windows of vulnerability to environmental exposures in the parental generation before conception or even in previous generations. There is evidence suggesting that information of prior exposures can be transferred across generations, and experimental animal models suggest that such transmission can be conveyed through epigenetic mechanisms. Although the molecular mechanisms of intergenerational and transgenerationational epigenetic transmission have yet to be determined, the realization that environment before conception can alter the risks of allergic diseases has profound implications for the development of public health interventions to prevent disease. Future research in both experimental models and in multigenerational human cohorts is needed to better understand the role of intergenerational and transgenerational effects in patients with asthma and allergic disease. This will provide the knowledge basis for a new approach to efficient intervention strategies aimed at reducing the major public health challenge of these conditions.

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“…Among these 1% CpG sites, most (~98%) DNA-M transmission is either dominated by the mother or transmitted evenly from mother and father. 23 …”

Section: Isle Of Wight 3rd Generation Cohortmentioning

confidence: 99%

Multigenerational cohorts in patients with asthma and allergy

Arshad

Karmaus

Zhang

et al. 2017

Journal of Allergy and Clinical Immunology

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Recent observations that disease risk can be transmitted across generations, without the need for a direct exposure of the child to the index environmental insult, has sparked interest in transgenerational inheritance. Epigenetic describes processes that modify gene expression without a change in the nucleotide sequence. Epigenetic processes can be induced in response to environmental exposures and can influence disease risk, and may explain these multigenerational effects. In experimental models, a number of epigenetic mechanisms have been identified that could mediate vertical transmission of epigenetic inheritance. However, relevance of these findings to human disease is not yet clear. An alternative model is where transgenerational inheritance of disease risk requires the presence of exposure-related diseases in the mother during pregnancy (termed 'induced epigenetic transmission model').A number of cross-sectional studies have investigated multigenerational effects in allergy and asthma. However, given early life origins of asthma and allergy, birth cohort studies are ideal to investigate the impact of genetic predisposition, epigenetics, and environmental exposures avoiding pitfalls such as recall bias and confounding by ongoing exposures, disease and treatment. The well characterized, three generations of the Isle of Wight cohort includes two consecutive birth cohorts, providing longitudinal data that can be studied for epigenetic transfer of information, e.g., the effect of grand parental smoking or exposure to other toxic compounds. Further large multigenerational birth cohorts are needed to establish the clinical relevance of this phenomenon and differentiate between vertical and induced transmission models, which may influence future preventive strategies.

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Identifying heterogeneous transgenerational DNA methylation sites via clustering in beta regression

Cited by 6 publications

References 29 publications

Identifying intergenerational patterns of correlated methylation sites

Identifying intergenerational patterns of correlated methylation sites

Transgenerational and intergenerational epigenetic inheritance in allergic diseases

Multigenerational cohorts in patients with asthma and allergy

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