Epigenome-wide exploratory study of monozygotic twins suggests differentially methylated regions to associate with hand grip strength

Soerensen, Mette; Li, Weilong; Debrabant, Birgit; Nygaard, Marianne; Mengel‐From, Jonas; Frost, Morten; Christensen, Kaare; Christiansen, Lene; Tan, Qihua

doi:10.1007/s10522-019-09818-1

Cited by 15 publications

(13 citation statements)

References 57 publications

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“…Given that AD is a typical disease of the nervous system that is associated with aging, we can reasonably predict the potential relationships between DLPFC and AD. On the basis of a monozygotic twin model, a study suggested that the demethylation of AMZ1 in DLPFC is associated with dyskinesia, another potential symptom of AD ( Soerensen et al, 2019 ). This report further confirmed the pathogenesis and downstream pathogenic regions of this methylation alteration.…”

Section: Discussionmentioning

confidence: 99%

Detecting Brain Structure-Specific Methylation Signatures and Rules for Alzheimer’s Disease

Guo

Zeng

et al. 2022

Front. Neurosci.

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Alzheimer’s disease (AD) is a progressive disease that leads to irreversible behavioral changes, erratic emotions, and loss of motor skills. These conditions make people with AD hard or almost impossible to take care of. Multiple internal and external pathological factors may affect or even trigger the initiation and progression of AD. DNA methylation is one of the most effective regulatory roles during AD pathogenesis, and pathological methylation alterations may be potentially different in the various brain structures of people with AD. Although multiple loci associated with AD initiation and progression have been identified, the spatial distribution patterns of AD-associated DNA methylation in the brain have not been clarified. According to the systematic methylation profiles on different structural brain regions, we applied multiple machine learning algorithms to investigate such profiles. First, the profile on each brain region was analyzed by the Boruta feature filtering method. Some important methylation features were extracted and further analyzed by the max-relevance and min-redundancy method, resulting in a feature list. Then, the incremental feature selection method, incorporating some classification algorithms, adopted such list to identify candidate AD-associated loci at methylation with structural specificity, establish a group of quantitative rules for revealing the effects of DNA methylation in various brain regions (i.e., four brain structures) on AD pathogenesis. Furthermore, some efficient classifiers based on essential methylation sites were proposed to identify AD samples. Results revealed that methylation alterations in different brain structures have different contributions to AD pathogenesis. This study further illustrates the complex pathological mechanisms of AD.

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Section: Discussionmentioning

confidence: 99%

Detecting Brain Structure-Specific Methylation Signatures and Rules for Alzheimer’s Disease

Guo

Zeng

et al. 2022

Front. Neurosci.

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“…DNA methylation levels for the cg05429895 (TLR4) probe were extracted from an existing methylation data set. DNA extraction, sample preparation, data processing, and DNA methylation using the Infinium Human Methylation 450K BeadChip was performed as descripted in [62]. Complete data was obtained for 140 samples.…”

Section: Replication Of the Correlation Between Methylation Grade Of Tlr4 And Depressive Symptom Gradementioning

confidence: 99%

“…Complete data was obtained for 140 samples. Blood leukocyte cell subtypes were counted using a Coulter LH 750 Haematology as previously described [62]. Gene expression levels for probes in the gene TLR4 (2 probes) were extracted from an existing genome-wide transcriptome data set.…”

Section: Replication Of the Correlation Between Methylation Grade Of Tlr4 And Depressive Symptom Gradementioning

confidence: 99%

Toll-like receptor 4 methylation grade is linked to depressive symptom severity

et al. 2021

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This study explores potential associations between the methylation of promoter-associated CpG sites of the toll-like receptor (TLR)-family, plasma levels of pro-inflammatory proteins and depressive symptoms in young female psychiatric patients. Ratings of depressive symptoms and blood samples were obtained from 92 young women seeking psychiatric care. Methylation of 32 promoter-associated CpG sites in TLR1 to TLR10 was analysed using the Illumina Infinium Methylation EPIC BeadChip. Expression levels of 91 inflammatory proteins were determined by proximity extension assay. Statistical correlations between depressive state, TLR1-10 methylation and inflammatory proteins were investigated. Four additional cohorts were studied to evaluate the generalizability of the findings. In the discovery cohort, methylation grade of cg05429895 (TLR4) in blood was inversely correlated with depressive symptoms score in young adults. After correction for multiple testing, plasma levels of macrophage inflammatory protein 1β (MIP-1β/CCL4) were associated with both TLR4 methylation and depressive symptom severity. A similar inverse association between TLR4 methylation in blood and affective symptoms score was also found in a cohort of 148 both males and females (<40 years of age) from the Danish Twin Registry. These findings were not, however, replicated in three other external cohorts; which differed from the first two cohorts by a higher age and mixed ethnicities, thus limiting the generalizability of our findings. However, TLR4 methylation inversely correlated with TLR4 mRNA expression in the Danish Twin Study indicating a functional significance of methylation at this particular CpG. Higher depression scores in young Scandinavian adults was associated with decreased methylation of TLR4 in blood.

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“…Anthropometric measures and whole blood samples were taken over the period from 2008 to 2011. Blood cell counts of 449 individuals were available and the blood cell counts of the other 9 individuals were imputed by the estimate CellCounts function in the R package minfi using DNA methylation data collected on the same blood samples [9,10].…”

Section: Samplesmentioning

confidence: 99%

Global Gene Expression Profiling of Body-Mass Index in Middle-Aged Danish Twins

Baumbach

Mohammadnejad³

et al. 2020

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Objective: The body mass index (BMI) measured as weight in relation to height is an important monitor for obesity and diabetes, with individual variation under control by genetic and environmental factors. In transcriptome-wide association studies on BMI, the genetic contribution calls for controlling of genetic confounding that affects both BMI and gene expression. We performed a global gene expression profiling of BMI on peripheral blood cells using monozygotic twins for efficient handling of genetic make-ups. Methods: We applied a generalized association method to genome-wide gene expression data on 229 pairs of monozygotic twins (age 56-80 years) for detecting diverse patterns of correlation between BMI and gene expression. Results: We detected seven probes associated with BMI with p<1e-04, among them two probes with p<1e05 (p=2.83e-06 AAK1; p=7.83e-06 LILRA3). In total, the analysis found 1579 probes with nominal p<0.05. Biological pathway analysis of enriched pathways found 50 KEGG and 45 Reactome pathways (FDR<0.05). The identified top functional pathways included immune function, JAK-STAT signalling, insulin signalling and regulation of energy metabolism. Conclusion: This transcriptome-wide association study using monozygotic twins and generalized correlation identified differentially expressed genes and a broad spectrum of enriched biological pathways that may implicate metabolic health.

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Epigenome-wide exploratory study of monozygotic twins suggests differentially methylated regions to associate with hand grip strength

Cited by 15 publications

References 57 publications

Detecting Brain Structure-Specific Methylation Signatures and Rules for Alzheimer’s Disease

Detecting Brain Structure-Specific Methylation Signatures and Rules for Alzheimer’s Disease

Toll-like receptor 4 methylation grade is linked to depressive symptom severity

Global Gene Expression Profiling of Body-Mass Index in Middle-Aged Danish Twins

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