A5061089999- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Child and Adolescent Psychosocial and Emotional Development
- Adolescent and Pediatric Healthcare
- Genetic Syndromes and Imprinting
- Genetic Associations and Epidemiology
- Cannabis and Cannabinoid Research
- Birth, Development, and Health
- Tryptophan and brain disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Child Development and Digital Technology
- Child Abuse and Trauma
- Adolescent Sexual and Reproductive Health
- RNA modifications and cancer
- Neuroendocrine regulation and behavior
- Family Support in Illness
- Genomic variations and chromosomal abnormalities
- Retirement, Disability, and Employment
- Sleep and related disorders
- Homelessness and Social Issues
- Genomics and Chromatin Dynamics
- Family Caregiving in Mental Illness
- Employment and Welfare Studies
- Neonatal Respiratory Health Research
King's College London
2015-2025
South London and Maudsley NHS Foundation Trust
2018
University of Exeter
2015
Abstract Background As the most stable and experimentally accessible epigenetic mark, DNA methylation is of great interest to research community. The landscape across tissues, through development in disease pathogenesis not yet well characterized. Thus there a need for rapid cost effective methods assessing genome-wide levels methylation. Illumina Infinium HumanMethylation450 (450K) BeadChip very useful addition available analysis but its complex design, incorporating two different assay...
Autism spectrum disorder (ASD) defines a group of common, complex neurodevelopmental disorders. Although the aetiology ASD has strong genetic component, there is considerable monozygotic (MZ) twin discordance indicating role for non-genetic factors. Because MZ twins share an identical DNA sequence, disease-discordant pairs provide ideal model examining contribution environmentally driven epigenetic factors in disease. We performed genome-wide analysis methylation sample 50 (100 individuals)...
DNA methylation is a key epigenetic mechanism involved in the developmental regulation of gene expression. Alterations are established contributors to inter-individual phenotypic variation and have been associated with disease susceptibility. The degree which changes loci-specific under influence heritable environmental factors largely unknown. In this study, we quantitatively measured across promoter regions dopamine receptor 4 (DRD4), serotonin transporter (SLC6A4/SERT) X-linked monoamine...
The association of histone modification changes with autism spectrum disorder (ASD) has not been systematically examined. We conducted a acetylome-wide study (HAWAS) by performing H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) on 257 postmortem samples from ASD and matched control brains. Despite etiological heterogeneity, ≥68% syndromic idiopathic cases shared common acetylome signature at >5,000 cis-regulatory elements in prefrontal temporal cortex. Similarly, multiple genes...
Epigenetic processes play a key role in orchestrating transcriptional regulation during development. The importance of DNA methylation fetal brain development is highlighted by the dynamic expression de novo methyltransferases perinatal period and neurodevelopmental deficits associated with mutations methyl-CpG binding protein 2 ( MECP2 ) gene. However, our knowledge about temporal changes to epigenome has, date, been limited. We quantified genome-wide patterns at ∼400,000 sites 179 human...
Abstract Monoamine oxidase A (MAOA) harbours a polymorphic upstream variable-number tandem repeat (u-VNTR). The MAOA-L allele of the u-VNTR leads to decreased gene expression levels in vitro and has been found increase risk conduct disorder males with childhood adversities. Early-life adversities have associated hypermethylation glucocorticoid receptor (NR3C1). In this study, we first performed genetic association analysis MAOA using individuals depression (n = 392) controls 1276). Next, DNA...
Variation in DNA methylation is being increasingly associated with health and disease outcomes. Although hypothesized to be a mechanism by which both genetic non-genetic factors can influence the regulation of gene expression, little known about extent at specific sites influenced heritable as well environmental factors. We quantified whole blood age 18 birth cohort 1,464 individuals comprising 426 monozygotic (MZ) 306 same-sex dizygotic (DZ) twin pairs. Site-specific levels were more...
Background Childhood adverse experiences are known to induce persistent changes in the hypothalamic–pituitary–adrenal (HPA) axis reactivity stress. However, mechanisms by which these shape neuroendocrine response stress remain unclear. Method We tested whether bullying victimization influenced serotonin transporter gene ( SERT ) DNA methylation using a discordant monozygotic (MZ) twin design. A subsample of 28 MZ pairs for victimization, with data on cortisol and methylation, were identified...
Objective: DNA methylation has been proposed as an epigenetic mechanism by which early-life experiences become “embedded” in the genome and alter transcriptional processes to compromise health. The authors sought investigate whether victimization stress is associated with genome-wide methylation. Method: tested hypothesis that Environmental Risk (E-Risk) Longitudinal Study, a nationally representative 1994–1995 birth cohort of 2,232 twins born England Wales assessed at ages 5, 7, 10, 12, 18...
Background Labour market disengagement among youths has lasting negative economic and social consequences, yet is poorly understood. We compared four types of work‐related self‐perceptions, as well vulnerability to mental health substance abuse problems, not in education, employment or training ( NEET ) their peers. Methods Participants were from the Environmental Risk (E‐Risk) longitudinal study, a nationally representative UK cohort 2,232 twins born 1994–1995. measured commitment work,...
Adolescent depression is a common neuropsychiatric disorder that often continues into adulthood and associated with wide range of poor outcomes including suicide. Although numerous studies have looked at genetic markers depression, the role epigenetic variation remains relatively unexplored.Monozygotic (MZ) twins were selected from an adolescent twin study designed to investigate interplay environmental factors in development emotional behavioral difficulties. There 18 pairs MZ identified...
Abstract Anxiety disorders that are the most commonly occurring psychiatric in childhood, associated with a range of social and educational impairments often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for majority cases, although up to 35–45% children do not achieve remission. Recent research suggests some genetic variants may be more beneficial response psychological therapy. Epigenetic mechanisms such as DNA methylation work at interface...
DNA methylation plays an important role in both normal human development and risk of disease. The most utilized method assessing uses BeadChips, generating epigenome-wide "snapshot" >450,000 observations (probe measurements) per assay. However, the reliability each these measurements is not equal, little consideration paid to consequences for research. We correlated repeat same samples using Illumina HumanMethylation450K Infinium MethylationEPIC BeadChips 350 blood samples. Probes that were...
This paper presents multilevel findings on adolescents' victimization exposure from a large longitudinal cohort of twins. Data were obtained the Environmental Risk (E-Risk) Longitudinal Twin Study, an epidemiological study 2,232 children (1,116 twin pairs) followed to 18 years age (with 93% retention). To assess adolescent victimization, we combined best practices in survey research with optimal approaches measuring life stress and traumatic experiences, introduce reliable system for coding...
Epigenetic processes such as DNA methylation have been implicated in the pathophysiology of neurodevelopmental disorders including schizophrenia and autism. changes can be induced by environmental exposures inflammation. Here we tested hypothesis that prenatal inflammation, a recognized risk factor for related conditions, alters key brain regions linked to schizophrenia, namely dopamine rich striatum endocrine regulatory centre, hypothalamus. across highly repetitive elements (long...
Background Hypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed investigate association between genetic epigenetics HPA cognitive behavior therapy (CBT). Methods Children with anxiety disorders were recruited into Genes for Treatment project (GxT, N = 1,152). Polymorphisms FKBP5 GR analyzed CBT. Percentage DNA methylation at promoter regions was measured...
The most widely utilized approaches for quantifying DNA methylation involve the treatment of genomic with sodium bisulfite; however, this method cannot distinguish between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Previous studies have shown that 5hmC is enriched in brain, although little known about its distribution how it differs anatomical regions individuals. In study, we combine oxidative bisulfite (oxBS) Illumina Infinium 450K BeadArray to quantify genome-wide patterns...
Autism spectrum disorder (ASD) is a phenotypically and genetically heterogeneous neurodevelopmental disorder. Despite this heterogeneity, previous studies have shown patterns of molecular convergence in post-mortem brain tissue from autistic subjects. Here, we integrate genome-wide measures mRNA expression, miRNA DNA methylation, histone acetylation ASD control brains to identify convergent subtype with shared dysregulation across both the epigenome transcriptome. Focusing on subtype,...
Autism spectrum disorder (ASD) encompasses a collection of complex neuropsychiatric disorders characterized by deficits in social functioning, communication and repetitive behaviour. Building on recent studies supporting role for developmentally moderated regulatory genomic variation the molecular aetiology ASD, we quantified genome-wide patterns DNA methylation 223 post-mortem tissues samples isolated from three brain regions [prefrontal cortex, temporal cortex cerebellum (CB)] dissected 43...
Abstract Research investigating associations between specific genes and individual differences with regards to the quality timing of sleep has primarily focussed on serotonin‐related clock genes. However, there are only a few studies this type most those date have not considered possibility gene–environment interaction. Here, we describe diurnal preference three functional polymorphisms: 5HTTLPR , PERIOD3 CLOCK 3111 . Furthermore, assessed whether genotypes phenotypes were moderated by...
Abstract Large-scale epigenome-wide association meta-analyses have identified multiple ‘signatures’’ of smoking. Drawing on these findings, we describe the construction a polyepigenetic DNA methylation score that indexes smoking behavior and can be utilized for purposes in population health research. To validate score, use data from two birth cohort studies: The Dunedin Longitudinal Study, followed to age-38 years, Environmental Risk age-18 years. show changes accumulate with increased...
Abstract Female somatic X-chromosome inactivation (XCI) balances the X-linked transcriptional dosages between sexes. Skewed XCI toward one parental X has been observed in several complex human traits, but extent to which genetics and environment influence skewed is largely unexplored. To address this, we quantify XCI-skew multiple tissues immune cell types a twin cohort. Within an individual, differs blood, fat skin tissue, shared across types. skew increases with age not other tissues,...