scholarly journals Neonatal DNA methylation and early-onset conduct problems: A genome-wide, prospective study

2017 ◽  
Vol 30 (2) ◽  
pp. 383-397 ◽  
Author(s):  
Charlotte A. M. Cecil ◽  
Esther Walton ◽  
Sara R. Jaffee ◽  
Tom O'Connor ◽  
Barbara Maughan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Conduct Problems ◽  
Early Onset ◽  
Pain Perception ◽  
Poor Mental Health ◽  
Monoamine Oxidase A ◽  
Fk506 Binding Protein ◽  
Parents And Children ◽  
A Genome ◽  
Using Data

AbstractEarly-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4–13 years), using data drawn from the Avon Longitudinal Study of Parents and Children. Methylomic variation at seven loci across the genome (false discovery rate < 0.05) differentiated children who go on to develop early-onset (n= 174) versus low (n= 86) CP, including sites in the vicinity of the monoglyceride lipase (MGLL) gene (involved in endocannabinoid signaling and pain perception). Subthreshold associations in the vicinity of three candidate genes for CP (monoamine oxidase A [MAOA], brain-derived neurotrophic factor [BDNF], and FK506 binding protein 5 [FKBP5]) were also identified. Within the early-onset CP group, methylation levels of the identified sites did not distinguish children who will go on to persist versus desist in CP behavior over time. Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic methylation quantitative trait loci. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP.

scholarly journals Epigenetic signatures associated with the observed link between maternal tobacco use during pregnancy, and offspring conduct problems in childhood and adolescence

2020 ◽  
Author(s):  
Alexandra J. Noble ◽  
John F. Pearson ◽  
Alasdair D. Noble ◽  
Joseph M. Boden ◽  
L. John Horwood ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Conduct Problems ◽  
Tobacco Use ◽  
Epigenetic Regulation ◽  
Tobacco Smoking ◽  
Maternal Smoking ◽  
In Utero ◽  
Smoking During Pregnancy ◽  
A Genome ◽  
Maternal Tobacco Use

AbstractBackgroundMetastable epialleles (MEs) are loci at which epigenetic regulation is established during development and subsequently maintained throughout life. Consequently, individuals can have the same genetic sequence, yet their epigenetic regulation of the underlying sequence can vary. MEs can be independent of genetic variation and may be induced by environmental exposures. Maternal tobacco smoking during pregnancy can alter offspring DNA methylation, hence there is potential for MEs to be induced during development in response to maternal tobacco smoking during pregnancy. Furthermore, associations between maternal tobacco use during pregnancy and conduct problems (CP) in offspring exposed to tobacco smoke in utero, have been observed. However, currently, we do not know what molecular mechanism may link these associations.ResultsWe investigated the observed link between maternal tobacco use during pregnancy and CP outcomes in exposed offspring. Individuals who were exposed to tobacco in utero via maternal smoking, and unexposed individuals, both with and without CP, were selected from the Christchurch Health and Development Study (CHDS), a longitudinal birth cohort studied for over 40 years in New Zealand. Bisulfite-based amplicon sequencing (BSAS) was used to investigate DNA methylation differences and potential MEs between the groups at high risk loci. We identified nominally significant differential DNA methylation at specific CpG sites in individuals with CP who were exposed to tobacco in utero. This differential methylation appears to be specific to in utero tobacco exposure, and interacts with CP. Given its association with the in utero environment we hypothesise that these methylation changes may represent MEs.ConclusionWe conclude that environmentally-induced DNA methylation differences may play a role in the observed link between maternal smoking during pregnancy and childhood/adolescent CP, potentially via the generation of MEs. Larger sample sizes and a genome-wide approach are required to investigate this association further.

scholarly journals Associations Between Developmental Timing of Child Abuse and Conduct Problem Trajectories

2020 ◽  
Author(s):  
Andreas Bauer ◽  
Gemma Hammerton ◽  
Abigail Fraser ◽  
Graeme Fairchild ◽  
Sarah L. Halligan
Keyword(s):  
Child Abuse ◽  
Conduct Problems ◽  
Early Onset ◽  
Latent Class ◽  
Developmental Stages ◽  
Developmental Trajectories ◽  
Conduct Problem ◽  
Self Report ◽  
Birth Cohort Study ◽  
Parents And Children

Abstract Background Although there is strong evidence for a relationship between child maltreatment and conduct problems, associations between child abuse experienced at different developmental stages and developmental trajectories of conduct problems have not been examined. We sought to investigate effects of timing of child abuse on conduct problem trajectories in a large UK-based birth cohort study. Methods We applied latent class growth analysis to identify conduct problem trajectories in the Avon Longitudinal Study of Parents and Children, using parent-rated conduct problems from ages 4-17 years (N=10648). Childhood-only and adolescence-only abuse, in addition to abuse in both developmental periods (‘persistent’ abuse), were assessed by retrospective self-report at age 22 years (N=3345). Results We identified four developmental trajectories: early-onset persistent (4.8%), adolescence-onset (4.5%), childhood-limited (15.4%), and low (75.3%) conduct problems. Childhood-only abuse and ‘persistent’ abuse were associated with increased odds of being on the early-onset persistent and adolescence-onset conduct problem trajectories compared to the low conduct problems trajectory. Adolescence-only abuse was not predictive of trajectory membership. There were no associations between abuse and childhood-limited trajectory membership.Conclusions Early-onset persistent and adolescence-onset conduct problems showed similar patterns of associations with abuse exposure, challenging developmental theories that propose qualitative, as opposed to quantitative, differences in environmental risk factors between these trajectories. The results also highlight that childhood-only and ‘persistent’ abuse were more strongly linked to elevated conduct problem trajectories than adolescence-only abuse, and that ‘persistent’ abuse is particularly detrimental.

scholarly journals Association between maladaptive parenting and child self-control over time: cross-lagged study using a monozygotic twin difference design

2012 ◽  
Vol 201 (4) ◽  
pp. 291-297 ◽  
Author(s):  
Charlotte A. M. Cecil ◽  
Edward D. Barker ◽  
Sara R. Jaffee ◽  
Essi Viding
Keyword(s):  
Conduct Problems ◽  
Parenting Practices ◽  
Community Sample ◽  
Monozygotic Twin ◽  
Self Control ◽  
Harsh Parenting ◽  
Early Interventions ◽  
Parents And Children ◽  
Using Data ◽  
Low Self Control

BackgroundHarsh parenting practices and negative parental feelings may be environmental risk factors for low self-control in children. Children may also evoke certain parenting reactions.AimsTo investigate the longitudinal relationship between parenting and self-control, as well as associated outcomes within the monozygotic (MZ) twin differences framework.MethodLongitudinal MZ twin differences analysis was conducted on a community sample of 5184 twins using data from ages 3, 4, 7 and 9 years. Outcomes related to self-control and parenting were analysed at age 12 years.ResultsNon-shared environmental effects of parenting on the development of self-control and an evocative effect of child self-control on parenting were found. Harsh parenting predicted conduct problems for both boys and girls. Self-control at age 9 predicted conduct problems and emotional difficulties at age 12.ConclusionsParenting and child self-control affect one another, highlighting the potential of early interventions that target parents and children simultaneously.

scholarly journals Grandmothers’ smoking in pregnancy is associated with a reduced prevalence of early-onset myopia

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Cathy Williams ◽  
Matthew Suderman ◽  
Jeremy A. Guggenheim ◽  
Genette Ellis ◽  
Steve Gregory ◽  
...  
Keyword(s):  
Early Onset ◽  
Late Onset ◽  
Prenatal Smoking ◽  
Vision Disorder ◽  
Smoking In Pregnancy ◽  
Parents And Children ◽  
Paternal Grandmother ◽  
Using Data ◽  
Methylation Patterns ◽  
In Pregnancy

Abstract Myopia (near sightedness) is the most common vision disorder resulting in visual impairment worldwide. We tested the hypothesis that intergenerational, non-genetic heritable effects influence refractive development, using grandparental prenatal smoking as a candidate exposure. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we found that the prevalence of myopia at age 7 was lower if the paternal grandmother had smoked in pregnancy, an association primarily found among grandsons compared to granddaughters. There was a weaker, non-sex-specific, reduction in the prevalence of myopia at age 7 if the maternal grandmother had smoked in pregnancy. For children who became myopic later (between 7 and 15 years of age) there were no associations with either grandmother smoking. Differences between early and late-onset myopia were confirmed with DNA methylation patterns: there were very distinct and strong associations with methylation for early-onset but not later-onset myopia.

Parent–Child Construction of Personal Memories in Reminiscing Conversations: Implications for the Development and Treatment of Childhood Psychopathology

2018 ◽  
Author(s):  
Karen Salmon
Keyword(s):  
Autobiographical Memory ◽  
Conduct Problems ◽  
Childhood Psychopathology ◽  
Relevant Research ◽  
The Past ◽  
Parents And Children ◽  
Emotion Competence ◽  
Critical Skills ◽  
Clinical Populations ◽  
Parent Child

Strong theory and research implicates parent–child conversations about the past in the child’s development of critical skills, including autobiographical memory and understanding of emotion and minds. Yet very little research has focused on associations between reminiscing and the development of childhood psychopathology. This chapter considers what is known about reminiscing between parents and children where there is anxiety or conduct problems. These findings provide clues as to how children come to manifest difficulties in autobiographical memory and emotion competence. Thereafter, the text reviews studies that have attempted to alter the style and content of parent–child reminiscing in clinical populations. The full implications of parent–child reminiscing, as a rich context for children’s development, have yet to be realized in clinically relevant research.

scholarly journals Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Pinpin Long ◽  
Qiuhong Wang ◽  
Yizhi Zhang ◽  
Xiaoyan Zhu ◽  
Kuai Yu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Coronary Syndrome ◽  
Methylation Level ◽  
Meta Analysis ◽  
Regulation Of Gene Expression ◽  
Density Lipoprotein ◽  
Blood Leukocytes ◽  
Coronary Syndrome ◽  
A Genome ◽  
Increased Risk

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.

scholarly journals Identification of DNA methylation signatures associated with poor outcome in lower-risk Stage, Size, Grade and Necrosis (SSIGN) score clear cell renal cell cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Louis Y. El Khoury ◽  
Shuang Fu ◽  
Ryan A. Hlady ◽  
Ryan T. Wagner ◽  
Liguo Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Renal Cell ◽  
Lower Risk ◽  
Clear Cell ◽  
Cell Cancer ◽  
Low Risk ◽  
Cell Renal Cell Carcinoma ◽  
A Genome ◽  
Size Grade ◽  
Prognostic Power

Abstract Background Despite using prognostic algorithms and standard surveillance guidelines, 17% of patients initially diagnosed with low risk clear cell renal cell carcinoma (ccRCC) ultimately relapse and die of recurrent disease, indicating additional molecular parameters are needed for improved prognosis. Results To address the gap in ccRCC prognostication in the lower risk population, we performed a genome-wide analysis for methylation signatures capable of distinguishing recurrent and non-recurrent ccRCCs within the subgroup classified as ‘low risk’ by the Mayo Clinic Stage, Size, Grade, and Necrosis score (SSIGN 0–3). This approach revealed that recurrent patients have globally hypermethylated tumors and differ in methylation significantly at 5929 CpGs. Differentially methylated CpGs (DMCpGs) were enriched in regulatory regions and genes modulating cell growth and invasion. A subset of DMCpGs stratified low SSIGN groups into high and low risk of recurrence in independent data sets, indicating that DNA methylation enhances the prognostic power of the SSIGN score. Conclusions This study reports a global DNA hypermethylation in tumors of recurrent ccRCC patients. Furthermore, DMCpGs were capable of discriminating between aggressive and less aggressive tumors, in addition to SSIGN score. Therefore, DNA methylation presents itself as a potentially strong biomarker to further improve prognostic power in patients with low risk SSIGN score (0–3).

scholarly journals Blood-Based Detection of Colorectal Cancer Using Cancer-Specific DNA Methylation Markers

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 51
Author(s):  
Nam-Yun Cho ◽  
Ji-Won Park ◽  
Xianyu Wen ◽  
Yun-Joo Shin ◽  
Jun-Kyu Kang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Sensitivity And Specificity ◽  
Stage Iv ◽  
High Sensitivity ◽  
Liquid Biopsies ◽  
Blood Leukocytes ◽  
Marker Panel ◽  
A Genome ◽  
Methylight Assay

Cancer tissues have characteristic DNA methylation profiles compared with their corresponding normal tissues that can be utilized for cancer diagnosis with liquid biopsy. Using a genome-scale DNA methylation approach, we sought to identify a panel of DNA methylation markers specific for cell-free DNA (cfDNA) from patients with colorectal cancer (CRC). By comparing DNA methylomes between CRC and normal mucosal tissues or blood leukocytes, we identified eight cancer-specific methylated loci (ADGRB1, ANKRD13, FAM123A, GLI3, PCDHG, PPP1R16B, SLIT3, and TMEM90B) and developed a five-marker panel (FAM123A, GLI3, PPP1R16B, SLIT3, and TMEM90B) that detected CRC in liquid biopsies with a high sensitivity and specificity with a droplet digital MethyLight assay. In a set of cfDNA samples from CRC patients (n = 117) and healthy volunteers (n = 60), a panel of five markers on the platform of the droplet digital MethyLight assay detected stages I–III and stage IV CRCs with sensitivities of 45.9% and 95.7%, respectively, and a specificity of 95.0%. The number of detected markers was correlated with the cancer stage, perineural invasion, lymphatic emboli, and venous invasion. Our five-marker panel with the droplet digital MethyLight assay showed a high sensitivity and specificity for the detection of CRC with cfDNA samples from patients with metastatic CRC.

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