scholarly journals Interaction of prenatal maternal smoking, interleukin 13 genetic variants and DNA methylation influencing airflow and airway reactivity

2013 ◽  
Vol 5 (1) ◽  
Author(s):  
Veeresh K Patil ◽  
John W Holloway ◽  
Hongmei Zhang ◽  
Nelis Soto-Ramirez ◽  
Susan Ewart ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genetic Variants ◽  
Maternal Smoking ◽  
Airway Reactivity ◽  
Interleukin 13 ◽  
Prenatal Maternal Smoking

scholarly journals DNA methylation links prenatal smoking exposure to later life health outcomes in offspring

2018 ◽  
Author(s):  
Petri Wiklund ◽  
Ville Karhunen ◽  
Rebecca C Richmond ◽  
Alina Rodriguez ◽  
Maneka De Silva ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Health Outcomes ◽  
Maternal Smoking ◽  
Psychiatric Morbidity ◽  
Later Life ◽  
Prenatal Smoking ◽  
Smoking During Pregnancy ◽  
Mediation Analyses ◽  
Increased Risk ◽  
Prenatal Maternal Smoking

AbstractMaternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship. To test this, we examined the association of prenatal maternal smoking with DNA methylation in 2,821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess, whether methylation markers have causal effects on disease outcomes in the offspring. We identify 69 differentially methylated CpGs in 36 genomic regions (P < 1×10−7), and show that DNA methylation may represent a biological mechanism through which maternal smoking is associated with increased risk of psychiatric morbidity in the exposed offspring.

scholarly journals Polymethylation Scores for Prenatal Maternal Smoke Exposure Persist Until Age 15 and Are Detected in Saliva

2021 ◽  
Author(s):  
Freida A Blostein ◽  
Jonah Fisher ◽  
John Dou ◽  
Lisa Schenper ◽  
Erin B Ware ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Standard Deviation ◽  
Maternal Smoking ◽  
Meta Analysis ◽  
Smoke Exposure ◽  
Receiver Operating Curve ◽  
P Value ◽  
Full Sample ◽  
Clinical Biomarkers ◽  
Prenatal Maternal Smoking

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.

scholarly journals Predicting Complex Traits and Exposures From Polygenic Scores and Blood and Buccal DNA Methylation Profiles

2021 ◽  
Vol 12 ◽  
Author(s):  
Veronika V. Odintsova ◽  
Valerie Rebattu ◽  
Fiona A. Hagenbeek ◽  
René Pool ◽  
Jeffrey J. Beck ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Complex Traits ◽  
Maternal Smoking ◽  
Smoking Status ◽  
Association Studies ◽  
Methylation Data ◽  
Polygenic Scores ◽  
Prenatal Maternal Smoking ◽  
Variance Explained

We examined the performance of methylation scores (MS) and polygenic scores (PGS) for birth weight, BMI, prenatal maternal smoking exposure, and smoking status to assess the extent to which MS could predict these traits and exposures over and above the PGS in a multi-omics prediction model. MS may be seen as the epigenetic equivalent of PGS, but because of their dynamic nature and sensitivity of non-genetic exposures may add to complex trait prediction independently of PGS. MS and PGS were calculated based on genotype data and DNA-methylation data in blood samples from adults (Illumina 450 K; N = 2,431; mean age 35.6) and in buccal samples from children (Illumina EPIC; N = 1,128; mean age 9.6) from the Netherlands Twin Register. Weights to construct the scores were obtained from results of large epigenome-wide association studies (EWASs) based on whole blood or cord blood methylation data and genome-wide association studies (GWASs). In adults, MSs in blood predicted independently from PGSs, and outperformed PGSs for BMI, prenatal maternal smoking, and smoking status, but not for birth weight. The largest amount of variance explained by the multi-omics prediction model was for current vs. never smoking (54.6%) of which 54.4% was captured by the MS. The two predictors captured 16% of former vs. never smoking initiation variance (MS:15.5%, PGS: 0.5%), 17.7% of prenatal maternal smoking variance (MS:16.9%, PGS: 0.8%), 11.9% of BMI variance (MS: 6.4%, PGS 5.5%), and 1.9% of birth weight variance (MS: 0.4%, PGS: 1.5%). In children, MSs in buccal samples did not show independent predictive value. The largest amount of variance explained by the two predictors was for prenatal maternal smoking (2.6%), where the MSs contributed 1.5%. These results demonstrate that blood DNA MS in adults explain substantial variance in current smoking, large variance in former smoking, prenatal smoking, and BMI, but not in birth weight. Buccal cell DNA methylation scores have lower predictive value, which could be due to different tissues in the EWAS discovery studies and target sample, as well as to different ages. This study illustrates the value of combining polygenic scores with information from methylation data for complex traits and exposure prediction.

scholarly journals Mediation by Placental DNA Methylation of the Association of Prenatal Maternal Smoking and Birth Weight

2019 ◽  
Vol 188 (11) ◽  
pp. 1878-1886 ◽  
Author(s):  
Andres Cardenas ◽  
Sharon M Lutz ◽  
Todd M Everson ◽  
Patrice Perron ◽  
Luigi Bouchard ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Maternal Smoking ◽  
Cell Types ◽  
Prenatal Smoking ◽  
Association Analyses ◽  
Lower Birth Weight ◽  
Cpg Sites ◽  
Prenatal Maternal Smoking ◽  
Infant Birth

Abstract Prenatal maternal smoking is a risk factor for lower birth weight. We performed epigenome-wide association analyses of placental DNA methylation (DNAm) at 720,077 cytosine-phosphate-guanine (CpG) sites and prenatal maternal smoking among 441 mother-infant pairs (2010–2014) and evaluated whether DNAm mediates the association between smoking and birth weight using mediation analysis. Mean birth weight was 3,443 (standard deviation, 423) g, and 38 mothers (8.6%) reported smoking at a mean of 9.4 weeks of gestation. Prenatal maternal smoking was associated with a 175-g lower birth weight (95% confidence interval (CI): −305.5, −44.8) and with differential DNAm of 71 CpGs in placenta, robust to latent-factor adjustment reflecting cell types (Bonferroni-adjusted P &lt; 6.94 × 10−8). Of the 71 CpG sites, 7 mediated the association between prenatal smoking and birth weight (on MDS2, PBX1, CYP1A2, VPRBP, WBP1L, CD28, and CDK6 genes), and prenatal smoking × DNAm interactions on birth weight were observed for 5 CpG sites. The strongest mediator, cg22638236, was annotated to the PBX1 gene body involved in skeletal patterning and programming, with a mediated effect of 301-g lower birth weight (95% CI: −543, −86) among smokers but no mediated effect for nonsmokers (β = −38 g; 95% CI: −88, 9). Prenatal maternal smoking might interact with placental DNAm at specific loci, mediating the association with lower infant birth weight.

scholarly journals Prenatal maternal smoking, maternal offending, and offspring behavioural and cognitive outcomes in early childhood

2018 ◽  
Vol 28 (5) ◽  
pp. 397-408 ◽  
Author(s):  
Stacy Tzoumakis ◽  
Vaughan J. Carr ◽  
Kimberlie Dean ◽  
Kristin R. Laurens ◽  
Maina Kariuki ◽  
...  
Keyword(s):  
Early Childhood ◽  
Maternal Smoking ◽  
Cognitive Outcomes ◽  
Prenatal Maternal Smoking

scholarly journals An integrative multi-omics approach in Sjögren’s Syndrome identifies novel genetic drivers with regulatory function and disease-specificity

2020 ◽  
Author(s):  
María Teruel ◽  
Guillermo Barturen ◽  
Manuel Martínez-Bueno ◽  
Miguel Barroso ◽  
Olivia Castelli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Sjögren’S Syndrome ◽  
Genetic Variants ◽  
Sjögren's Syndrome ◽  
Expression Patterns ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Regulatory Function ◽  
Sjögren‘S Syndrome

ABSTRACTPrimary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study we identified vast coordinated hypomethylation and overexpression effects, that also exhibit increased variability, in many already known IFN-regulated genes. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of novel genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified new genetic variants associated with SS that mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, DNA methylation, gene expression and SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population.

scholarly journals GSDMA drives the most replicated association with asthma in naïve CD4+ T cells

2019 ◽  
Author(s):  
Anne-Marie Madore ◽  
Lucile Pain ◽  
Anne-Marie Boucher-Lafleur ◽  
Jolyane Meloche ◽  
Andréanne Morin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
T Cells ◽  
Genetic Variants ◽  
Immune Cell ◽  
Cell Types ◽  
Sequencing Data ◽  
Opposite Pattern ◽  
Genetic Mechanisms ◽  
New Gene

AbstractBackgroundThe 17q12-21 locus is the most replicated association with asthma. However, no study had described the genetic mechanisms underlying this association considering all genes of the locus in immune cell samples isolated from asthmatic and non-asthmatic individuals.ObjectiveThis study takes benefit of samples from naïve CD4+ T cells and eosinophils isolated from the same 200 individuals to describe specific interactions between genetic variants, gene expression and DNA methylation levels for the 17q12-21 asthma locus.Methods and ResultsAfter isolation of naïve CD4+ T cells and eosinophils from blood samples, next generation sequencing was used to measure DNA methylation levels and gene expression counts. Genetic interactions were then evaluated considering genetic variants from imputed genotype data. In naïve CD4+ T cells but not eosinophils, 20 SNPs in the fourth and fifth haplotype blocks modulated both GSDMA expression and methylation levels, showing an opposite pattern of allele frequencies and expression counts in asthmatics compared to controls. Moreover, negative correlations have been measured between methylation levels of CpG sites located within the 1.5 kb region from the transcription start site of GSDMA and its expression counts.ConclusionAvailability of sequencing data from two key cell types isolated from asthmatic and non-asthmatic individuals allowed identifying a new gene in naïve CD4+ T cells that drives the association with the 17q12-21 locus, leading to a better understanding of the genetic mechanisms taking place in it.

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