scholarly journals Exposure to violence, chronic stress, nasal DNA methylation, and atopic asthma in children

Author(s):  
Qi Yan ◽  
Erick Forno ◽  
Andres Cardenas ◽  
Cancan Qi ◽  
Yueh-Ying Han ◽  
...  

ABSTRACTBackgroundExposure to violence (ETV) or stress may cause asthma through unclear mechanisms.MethodsEpigenome-wide association study (EWAS) of DNA methylation in nasal epithelium and four ETV or chronic stress measures in 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed measures of ETV or chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Each EWAS was conducted using linear regression, with CpGs as dependent variables and the stress/violence measure as a predictor, adjusting for age, sex, the top five principal components, and SVA latent factors. We then selected the top 100 CpGs (by P-value) associated with each stress/violence measure in EVA-PR and conducted a meta-analysis of the selected CpGs and atopic asthma using data from EVA-PR and two additional cohorts (Project Viva and PIAMA).ResultsIn the EWAS of stress/violence in EVA-PR, gun violence was associated with methylation of cg18961589 in LINC01164 (β=0.03, P=1.28×10−7), and maternal stress was associated with methylation of cg03402351 in SNN (β=0.04, P=1.69×10−7) and cg19064846 in PTPRN2 (β=0.03, P=3.36×10−7). In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence in EVA-PR, CpGs in STARD3NL, SLC35F4, TSR3, CDC42SE2, KLHL25, PLCB1, BUD13, OR2B3, GALR1, TMEM196, TEAD4 and ANAPC13 were associated with atopic asthma at FDR-P < 0.05.ConclusionsETV and chronic stress may increase the risk of atopic asthma through DNA methylation in airway epithelium, though this needs confirmation in future longitudinal studies.

2021 ◽  
Author(s):  
Qi Yan ◽  
Erick Forno ◽  
Andres Cardenas ◽  
Cancan Qi ◽  
Yueh‐Ying Han ◽  
...  

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii65-iii66
Author(s):  
M Q S Mosella ◽  
T S Sabedot ◽  
T M Malta ◽  
J Rock ◽  
M Felicella ◽  
...  

Abstract BACKGROUND Despite histologically benign, pituitary tumors (PT) may invade important adjacent neurovascular structures which can incur in significant comorbidities preventing a complete surgical resection and contributing to resistance to medical treatment. DNA methylation clearly stratified PT based on their functional status i.e. nonfunctioning PTs (NFPTs) from functioning PT (FPTs). However associations of methylation aberrations with invasive behavior is less clear. MATERIAL AND METHODS In order to evaluate whether DNA methylation alterations in regulatory regions other than promoter and coding regions are associated with invasive behavior we performed a meta-analysis of the genome-wide methylome of three public available PT cohorts plus our own (Illumina HumanMethylation platforms- 450K/EPIC). Pituitary specimens comprised of 43 invasive pituitary tumors (InvPT) and 37 noninvasive (NInvPT); 12 FPT and 68 NFPTs, in addition to 20 non-tumor pituitaries. RNA-seq data were available for one cohort (n=23, 12 InvPT,11NInvPT) and integrated with DNA methylation. Invasiveness criteria was based on Knosp grade >= 2 and/or sphenoid or dural invasion. RESULTS Wilcoxon Rank-sum test; Δβ=0.15; p-value <0.001 identified 58 differentially methylated CpG sites in InvPT that were mainly hypomethylated (95%) in relation to NInvPT. NInvPT methylation profile was similar to non-tumor specimens, despite its heterogeneity. Thirty-four percent (n=20) of the differentially methylated CpG sites were located within predicted enhancer regions distributed in intronic (40%), intergenic (40%) and promoter (20%) regions. Predicted enhancer-target genes were enriched for actin filament cell movement, response to starvation, growth factor stimulus and protein autophosporilation pathways. Among them, ZNF625 and INO80E were found mostly negative correlated among methylation and expression data (-0.50 and -0.48, respectively), besides DOC2A found to be one potentially differentially expressed gene under enhancer control (log2FC > 0.2, pvalue <0.05). CONCLUSION Our results suggest that methylation alterations in predicted regulatory regions, such as enhancers, annotated in non-promoter regions (introns and intergenic) may contribute to the invasive behavior of PT.


2021 ◽  
Author(s):  
Freida A Blostein ◽  
Jonah Fisher ◽  
John Dou ◽  
Lisa Schenper ◽  
Erin B Ware ◽  
...  

Background: Prenatal maternal smoking has negative implications for child health. DNA methylation signatures can function as biomarkers of prenatal maternal smoking. However little work has assessed how DNA methylation signatures of prenatal maternal smoking vary across ages, ancestry groups, or tissues. In the Fragile Families and Child Wellbeing study, we tested whether prenatal maternal smoking was associated with salivary polymethylation scores for smoking in participants. We assessed the consistency of associations at ages 9 and 15, their portability across participants from African, European, and Hispanic genetic ancestries and the accuracy of exposure classification using area under the curve (AUC) from receiver operating curve analyses. Results: We created saliva polymethylation scores using coefficients from a meta-analysis of prenatal maternal smoke exposure and DNA methylation in newborn cord blood. In the full sample at age 9 (n=753), prenatal maternal smoke exposure was associated with a 0.52 (95%CI: 0.36, 0.67) standard deviation higher polymethylation score for prenatal smoke exposure The direction and magnitude of the association was consistent when stratified by genetic ancestries. In the full sample at age 15 (n=746), prenatal maternal smoke exposure was associated with a 0.46 (95%CI: 0.3, 0.62) standard deviation higher polymethylation score for prenatal smoke exposure, and the effect size was attenuated among the European and Hispanic genetic ancestry samples. The polymethylation score was reasonably accurate at classifying prenatal maternal smoke exposure (AUC age 9=0.77, P value<0.001, age 15=0.77, P value<0.001). The polymethylation score showed higher classification accuracy than using a single a priori site in the AHRR gene (cg05575921 AUC=0.74, P value=0.03; age 15=0.73, P value=0.01). Conclusions: Prenatal maternal smoking was associated with DNA methylation signatures in saliva samples, a clinically practical tissue. Polymethylation scores for prenatal maternal smoking were portable across genetic ancestries and more accurate than individual DNA methylation sites. DNA polymethylation scores from saliva samples could serve as robust and practical clinical biomarkers of prenatal maternal smoke exposure.


2018 ◽  
Author(s):  
Jun Liu ◽  
Elena Carnero-Montoro ◽  
Jenny van Dongen ◽  
Samantha Lent ◽  
Ivana Nedeljkovic ◽  
...  

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of the functional relevance of the phenomenon remains limited. Because obesity is the main risk factor for T2D and a driver of methylation from previous study, we aimed to explore the effect of DNA methylation in the early phases of T2D pathology while accounting for body mass index (BMI). We performed a blood-based epigenome-wide association study (EWAS) of fasting glucose and insulin among 4,808 non-diabetic European individuals and replicated the findings in an independent sample consisting of 11,750 non-diabetic subjects. We integrated blood-based in silico cross-omics databases comprising genomics, epigenomics and transcriptomics collected by BIOS project of the Biobanking and BioMolecular resources Research Infrastructure of the Netherlands (BBMRI-NL), the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium, and the tissue-specific Genotype-Tissue Expression (GTEx) project. We identified and replicated nine novel differentially methylated sites in whole blood (P-value < 1.27 × 10-7): sites in LETM1, RBM20, IRS2, MAN2A2 genes and 1q25.3 region were associated with fasting insulin; sites in FCRL6, SLAMF1, APOBEC3H genes and 15q26.1 region were associated with fasting glucose. The association between SLAMF1, APOBEC3H and 15q26.1 methylation sites and glucose emerged only when accounted for BMI. Follow-up in silico cross-omics analyses indicate that the cis-acting meQTLs near SLAMF1 and SLAMF1 expression are involved in glucose level regulation. Moreover, our data suggest that differential methylation in FCRL6 may affect glucose level and the risk of T2D by regulating FCLR6 expression in the liver. In conclusion, the present study provided nine new DNA methylation sites associated with glycemia homeostasis and also provided new insights of glycemia related loci into the genetics, epigenetics and transcriptomics pathways based on the integration of cross-omics data in silico.


2020 ◽  
Author(s):  
Doretta Caramaschi ◽  
James Jungius ◽  
Christian M. Page ◽  
Boris Novakovic ◽  
Richard Saffery ◽  
...  

AbstractStudy questionIs DNA methylation at birth associated with having been conceived by assisted reproductive technologies (ART)?Summary answerThis study shows does not provide strong evidence of an association of conception by ART with variation in infant blood cell DNA methylation.What is known alreadyAssisted reproductive technologies (ART) are procedures used to help infertile/subfertile couples conceive. Due to its importance in gene regulation during early development programming, DNA methylation and its perturbations associated with ART could reveal new insights into the biological effects of ART and potential adverse offspring outcomes.Study designWe investigated the association of DNA methylation and ART using a case-control study design (N=205 ART cases and N=2439 non-ART controls in discovery cohorts; N=149 ART cases and N=58 non-ART controls in replication cohort).Participants/materials, settings, methodWe assessed the association between ART and DNA methylation at birth in cord blood (205 ART conceptions and 2439 naturally conceived controls) at >450000 CpG sites across the genome in two sub-samples of the UK Avon Longitudinal Study of Parents and Children (ALSPAC) and two sub-samples of the Norwegian Mother, Father and Child Cohort Study (MoBa) by meta-analysis. We explored replication of findings in the Australian Clinical review of the Health of adults conceived following Assisted Reproductive Technologies (CHART) study (N=149 ART conceptions and N=58 controls).Main results and the role of chanceThe ALSPAC and MoBa meta-analysis revealed evidence of association between conception by ART and DNA methylation (false-discovery-rate-corrected p-value < 0.05) at 5 CpG sites which are annotated to 2 genes. Methylation at 3 of these sites has been previously linked to cancer, aging, HIV infection and neurological diseases. None of these associations replicated in the CHART cohort. There was evidence of a functional role of ART-induced hypermethylation at CpG sites located within regulatory regions as shown by putative transcription factor binding and chromatin remodelling.Limitations, reasons for cautionsWhile insufficient power is likely, heterogeneity in types of ART and between populations may also contribute. Larger studies might identify replicable variation in DNA methylation at birth due to ART.Wider implications of the findingsART-conceived newborns present with divergent DNA methylation in cord blood white cells. If these associations are true and causal, they might have long-term consequences for offspring health.


2008 ◽  
Vol 31 (4) ◽  
pp. 11
Author(s):  
Manda Ghahremani ◽  
Courtney W Hannah ◽  
Maria Peneherrera ◽  
Karla L Bretherick ◽  
Margo R Fluker ◽  
...  

Background/Purpose: Premature ovarian failure (POF) affects 1% of women with a largely idiopathic and poorly understood etiology. The objective of this study was to identify specific epigenetic alterations by measuring DNA methylation of gene regulatory regions in women with POF vs. controls. Methods: Blood samples were collected from idiopathic POFpatients (Amenorrhea for at least 3 months and 2 serum FSH levels of > 40mIU/ml obtained > 1 month apart prior to age 40) and control women (CW) (healthy pregnancy after age 37 with out a pregnancy loss). Genomic DNA was extracted from EDTA anticoagulated blood and bisulfite converted for analysis using the Illumina Golden Gate Methylation Panel which measures DNA methylation at 1506 CpG sites in the promoter regions of 807 genes in 10 POF and 12 CW. Candidate genes with altered epigenetic marks between POF and CW at a nominal P-value < 0.05 were identified using a t-testcomparison within the Illumina bead studio software. Genes of interest were further analyzed for quantitative methylation at specific CpG sites using pyrosequencing in 30 POF and 30 CW. Results: Comparison of DNA methylation profiles of our initial POF and CW groups identified several genes with statistically significanthyper- or hypo- methylation in the POF group (P < 0.05), including the Androgen Receptor (AR)promoter region, which was significantly hypermethylated. To further validate these results, DNA methylation of the AR gene promoter was quantified bypryosequencing in a larger group of POF and CW. Pyrosequencing further confirmed a significantly higher DNA methylation of the AR promoter region inPOF vs. CW (P=0.007). Conclusions: This is a novel study identifying epigenetic alterations in POF. The hypermethylation of the AR gene in POF patients may cause decreased level of the AR in these women. This is especially interesting given a recent report of induced POF in AR deficient mice^1. Specific epigenetic markers, as identified by DNA methylation array profiling in blood, may serve as useful biomarkers for POF and other fertility disorders. However, it will need to be determined if these methylation changes are present prior to diagnosis, or are a consequence of menopause itself. Reference: 1.Hiroko S. et al. Premature ovarian failure in androgenreceptor deficient mice. PNAS;103:224-9


2020 ◽  
Vol 17 (1) ◽  
pp. 82-93
Author(s):  
Mary-Joe Youssef ◽  
Antoine Aoun ◽  
Aline Issa ◽  
Lana El-Osta ◽  
Nada El-Osta ◽  
...  

Background: The prevalence of gastroesophageal reflux disease (GERD) is increasing worldwide and the related chronic symptoms can be associated with morbidity and poor quality of life. Objective: The objective of this study was to identify foods and beverages consumed by the Lebanese population, dietary habits, socio-demographic and lifestyle factors, health parameters and perceived stress, implicated in increasing GERD symptoms. Methods: This observational cross-sectional study was carried among Lebanese adults in 2016. A convenient sample of 264 participants was equally divided into a GERD group and a control group. Data on socio-demographic characteristics, lifestyle, health status and dietary habits including Lebanese traditional dishes were collected. The perceived stress scale (PSS) was also used to assess the participants’ perception of stress. Logistic regression analyses were conducted with GERD symptoms (presence or absence) being the dependent variable. Results: The GERD symptoms were significantly associated with age (-p-value=0.017), family history of GERD symptoms (-p-value<0.001), smoking (-p-value=0.003) and chronic medical conditions (-p-value<.001). Regarding the dietary factors, participants who ate three meals or less/day, between meals and outside homes were 2.5, 2.9 and 2.4 times at a higher risk of experiencing GERD symptoms than others, respectively. Moreover, the logistic regression model showed that the GERD symptoms were significantly associated with the consumption of coffee (-p-value=0.037), Lebanese sweets (-p-value=0.027), fried foods (-p-value=0.031), ‘Labneh’ with garlic (-p-value<0.001), pomegranate molasses (-p-value=0.011), and tomatoes (-p-value=0.007). Conclusion: Some specific lifestyle factors and components of the Lebanese Mediterranean diet could be associated with GERD symptoms.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Pinpin Long ◽  
Qiuhong Wang ◽  
Yizhi Zhang ◽  
Xiaoyan Zhu ◽  
Kuai Yu ◽  
...  

Abstract Background Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear. Methods We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study. Results We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02–1.48; P = 0.03). Conclusions We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.


Author(s):  
Manuel Chavarrias ◽  
Santos Villafaina ◽  
Ana Myriam Lavín-Pérez ◽  
Jorge Carlos-Vivas ◽  
Eugenio Merellano-Navarro ◽  
...  

Background and objectives: Obesity or overweight is associated with many health risk factors and preventable mortality. Even people with normal weight and without history of obesity or overweight should avoid weight gain to reduce health risks factors. In this regard Latin aerobic dances involved in Zumba® practice make this modality motivating for people. Apart from weight loss and VO2peak benefits, Zumba practice is also interesting by the increase in adherence which can also avoid weight regain. The aim was to systematically review the scientific literature about the effects of any randomized intervention of Zumba® practice on total fat mass (%) and maximum oxygen consumption (VO2peak), besides establishing directions for the clinical practice. Evidence acquisition: Two systematic searches were conducted in two electronic databases following the PRISMA guidelines. The eligibility criteria were (a) outcomes: body mass or VO2peak data including mean and standard deviation (SD) before and after Zumba® intervention, (b) study design: randomized controlled trial (RCT) and (c) language: English. GRADE guidelines were used to assess the quality of evidence. A meta-analysis was performed to determine mean differences. Nine and four studies were selected for fat mass percentage and VO2peak in the systematic review, respectively. However, only eight studies for fat mass percentage and three for VO2peak could be included in the meta-analysis. Evidence synthesis: The overall standardized mean difference for fat mass was −0.25 with a 95% CI from −0.67 to 0.16 with a p-value of 0.69, with large heterogeneity. On the other hand, the overall effect size for VO2peak was 0.53 (95% CI from 0.04 to 1.02 with a p-value of 0.03) with large heterogeneity. Conclusions: Based on the evidence, we cannot conclude that Zumba® is effective at reducing body mass but it may improve VO2peak. However, the limited number of studies that met the inclusion criteria makes it too early to reach a definite conclusion, so more research is needed.


2021 ◽  
pp. 1-5
Author(s):  
Richard W. Bohannon

BACKGROUND AND OBJECTIVE: Numerous studies have addressed the relationship between paretic knee extension strength and comfortable walking speed after stroke. However, the correlations reported are highly variable. This review sought to summarize the correlational data using meta-analysis. METHODS: Relevant literature was identified via a search of 3 bibliographic databases. Articles were screened and perused for inclusion. Included articles were examined for information on the sample studied, procedures for measuring strength and gait speed, and correlations reported between the 2 variables. Meta-analysis was used to calculate a summary correlation. RESULTS: Of 299 unique articles, 18 met inclusion criteria. Articles were diverse in regard to samples studied, procedures described, and correlations reported. Meta-analysis using data from all included studies revealed a summary correlation of 0.51. For studies using hand-held or isokinetic dynamometry, the summary correlation was 0.46 and 0.59 respectively. CONCLUSIONS: This study provides a better indication of the correlation between paretic knee extension strength and comfortable gait speed than individual studies. The correlation is high enough to provide support for the routine measurement of paretic knee extension force for individuals who have experienced a stroke.


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