Evaluation of the usefulness of saliva for DNA methylation analysis in cohort studies

Murata, Y.; Fujii, Ayaka; Kanata, Sho; Fujikawa, Shinya; Ikegame, Tempei; Nakachi, Yutaka; Zhao, Zhilei; Jinde, Seiichiro; Kasai, Kiyoto; Bundo, Miki; Iwamoto, Kazuya

doi:10.1002/npr2.12075

Cited by 16 publications

(12 citation statements)

References 22 publications

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“…While mouse epigenetic studies of behavior can involve brain tissues, such tissues are impossible to collect in humans except from human brain banks. Instead, people who study epigenetic regulation of behavior in humans utilize a surrogate tissue such as blood or saliva which can be collected in non-invasive manners ( Solomon et al., 2018 ; Murata et al., 2019 ). Other tissues have been collected in humans for epigenetic studies, such as fat or muscle biopsies ( Taylor et al., 2019 ), but such collections are much more invasive than collecting blood or saliva and consequently more difficult to collect.…”

Section: Methodsmentioning

confidence: 99%

DNA methylation and exposure to violence among African American young adult males

Saadatmand

Gurdziel

Jackson

et al. 2021

Brain, Behavior, & Immunity - Health

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Exposure to violence (ETV) has been linked to epigenomics mechanisms such as DNA methylation (DNAm). We used epigenetic profiling of blood collected from 32 African American young adult males who lived in Washington DC to determine if changes in DNAm at CpG sites affiliated with nervous and immune system were associated with exposure to violence. Pathway analysis of differentially methylated regions comparing high and low ETV groups revealed an enrichment of gene sets annotated to nervous system and immune ontologies. Many of these genes are known to interact with each other which suggests DNAm alters gene function in the nervous and immune system in response to ETV. Using data from a unique age group, young African American adult males, we provide evidence that lifetime ETV could impact DNA methylation in genes impacted at Central Nervous System and Immune Function sites. Method Methylation analysis was performed on DNA collected from the blood of participants classified with either high or low lifetime ETV. Illumina®MethylationEPIC Beadchips (~850k CpG sites) were processed on the iScan System to examine whole-genome methylation differences. Differentially methylated CpG-sites between high (n = 19) and low (n = 13) groups were identified using linear regression with violence and substance abuse as model covariates. Gene ontology analysis was used to identify enrichment categories from probes annotated to the nearest gene. Results A total of 595 probes (279 hypermethylated; 316 hypomethylated) annotated to 383 genes were considered differentially methylated in association with ETV. Males with high ETV showed elevated methylation in several signaling pathways but were most impacted at Central Nervous System and Immune Function affiliated sites. Eight candidate genes were identified that play important biological roles in stress response to violence with HDAC4 (10%), NR4A3 (11%), NR4A2 (12%), DSCAML1(12%), and ELAVL3 (13%) exhibiting higher levels in the low ETV group and DLGAP1 (10%), SHANK2 (10%), and NRG1(11%) having increased methylation in the high ETV group. These findings suggest that individuals subjected to high ETV may be at risk for poor health outcomes that have not been reported previously.

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Section: Methodsmentioning

confidence: 99%

DNA methylation and exposure to violence among African American young adult males

Saadatmand

Gurdziel

Jackson

et al. 2021

Brain, Behavior, & Immunity - Health

View full text Add to dashboard Cite

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“…Moreover, saliva collection is clearly less invasive and without the risks potentially occurring when using blood [33]. Remarkably, good quality DNA can be easily isolated from saliva and used not only for genetic studies [34] but also for epigenetic analysis [35][36][37][38][39]. Finally, salivary microbiota is stable enough for analysis of its composition, partly overlaps with gut microbiota and is affected by diet and lifestyle [40,41].…”

Section: Introductionmentioning

confidence: 99%

Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis

et al. 2022

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Background Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies.

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“…These include all-cause mortality, cancers, health span, physical functioning and Alzheimer’s disease, above and beyond what is explained by chronological time [ 23 ]. We used saliva as a suitable, comparable and less invasive means of sample collection [ 24 ]. The PhenoAge clock is based on age-related DNAm levels at 513 CpG sites, more CpG sites than any other epigenetic clock, to estimate the biological age across multiple tissues and cells.…”

Section: Introductionmentioning

confidence: 99%

Reduction in Epigenetic Age Acceleration Is Related to Empathy in Mothers with Neglectful Caregiving

et al. 2021

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DNA methylation clocks are used as molecular estimators of epigenetic age, but with little evidence in mothers and none in neglectful mothering. We investigated differences in epigenetic age acceleration (EAA) and the role of empathy using the PhenoAge clock. We collected saliva samples from mothers with extreme disregard for their child’s needs (50 in the neglect group, NG) and mothers with non-neglectful caregiving (87 in the control group, CG). Mothers completed an empathy scale, along with questionnaires of their own childhood maltreatment, adverse life events and psychiatric disorders. Sociodemographic variables potentially affecting EAA were also measured. The ANCOVA solution showed a significant increase in EAA in the NG compared to the CG, after adjustment for maternal age, number of pregnancies, financial assistance, adverse events, childhood maltreatment and psychiatric disorder. The group interaction effects showed a reduction in EAA for greater empathic concern and for a higher education level both as positive factors, and an increment in EAA for mothers living in a two-parent family as a risk factor, all in the NG. Our findings open the search for protective factors of EAA associated with caregiver behavior to reduce health vulnerabilities and poor social functioning, especially for mothers at risk of maladaptive caregiving.

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Evaluation of the usefulness of saliva for DNA methylation analysis in cohort studies

Cited by 16 publications

References 22 publications

DNA methylation and exposure to violence among African American young adult males

DNA methylation and exposure to violence among African American young adult males

Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis

Reduction in Epigenetic Age Acceleration Is Related to Empathy in Mothers with Neglectful Caregiving

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