A5020002548- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Genetic Associations and Epidemiology
- Diet and metabolism studies
- Intergenerational Family Dynamics and Caregiving
- Schizophrenia research and treatment
- Genetics and Neurodevelopmental Disorders
- Birth, Development, and Health
- Pancreatic function and diabetes
- Family Caregiving in Mental Illness
- Dementia and Cognitive Impairment Research
- Identity, Memory, and Therapy
- Neonatal Respiratory Health Research
- Cannabis and Cannabinoid Research
- Health, Environment, Cognitive Aging
- Cancer-related gene regulation
- Single-cell and spatial transcriptomics
- Congenital heart defects research
- Cognitive Abilities and Testing
- Adolescent and Pediatric Healthcare
- Pluripotent Stem Cells Research
- Mitochondrial Function and Pathology
- Child and Adolescent Psychosocial and Emotional Development
- DNA and Nucleic Acid Chemistry
- Tryptophan and brain disorders
University of Exeter
2015-2024
Royal Devon and Exeter Hospital
2019-2024
South London and Maudsley NHS Foundation Trust
2018
King's College London
2018
University of Bristol
2018
University of Edinburgh
1897-2012
Wellcome Centre for Cell Biology
2012
Schizophrenia is a highly heritable, neuropsychiatric disorder characterized by episodic psychosis and altered cognitive function. Despite success in identifying genetic variants associated with schizophrenia, there remains uncertainty about the causal genes involved disease pathogenesis how their function regulated.We performed multi-stage epigenome-wide association study, quantifying genome-wide patterns of DNA methylation total 1714 individuals from three independent sample cohorts. We...
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...
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...
Characterizing the complex relationship between genetic, epigenetic, and transcriptomic variation has potential to increase understanding about mechanisms underpinning health disease phenotypes. We undertook a comprehensive analysis of common genetic on DNA methylation (DNAm) by using Illumina EPIC array profile samples from UK Household Longitudinal study. identified 12,689,548 significant quantitative trait loci (mQTL) associations (p < 6.52 × 10-14) occurring 2,907,234 variants 93,268...
Abstract Human DNA methylation data have been used to develop biomarkers of ageing, referred as ‘epigenetic clocks’, which widely identify differences between chronological age and biological in health disease including neurodegeneration, dementia other brain phenotypes. Existing clocks shown be highly accurate blood but are less precise when older samples or tissue types not included training the model, brain. We aimed a novel epigenetic clock that performs optimally human cortex has...
Inflammatory bowel diseases (IBDs) are heterogeneous disorders with complex aetiology. Quantitative genetic studies suggest that only a small proportion of the disease variance observed in IBD is accounted for by variation, indicating potential role differential epigenetic regulation The aim this study was to assess genome-wide DNA methylation changes specifically associated ulcerative colitis (UC), Crohn's (CD) and activity.DNA quantified peripheral blood mononuclear cells (PBMCs) from 149...
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 Background The Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile unknown samples and has been used to calculate “age acceleration” various tissues environments. Results model systematically underestimates older people. This seen all examined but most strongly cerebellum consistently observed multiple datasets. Age acceleration thus age-dependent, this can lead spurious associations. current literature includes...
Alzheimer's disease is a progressive neurodegenerative disorder that hypothesized to involve epigenetic dysfunction. Previous studies of DNA modifications in have been unable distinguish between methylation and hydroxymethylation. hydroxymethylation has shown be enriched the human brain, although its role not yet fully explored. Here, we utilize oxidative bisulfite conversion, conjunction with Illumina Infinium Human Methylation 450K microarray, identify neuropathology-associated...
Accelerated DNA methylation age is linked to all-cause mortality and environmental factors, but studies of associations with socioeconomic position are limited. Researchers generally use small selected samples, it unclear how findings obtained 2 commonly used methods for calculating (the Horvath method the Hannum method) translate general population samples including younger older adults. Among 1,099 United Kingdom adults aged 28-98 years in 2011-2012, we assessed relationship acceleration a...
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...
Abstract Alzheimer’s disease (AD) is a chronic neurodegenerative characterized by the progressive accumulation of amyloid-beta and neurofibrillary tangles tau in neocortex. We profiled DNA methylation two regions cortex from 631 donors, performing an epigenome-wide association study multiple measures AD neuropathology. meta-analyzed our results with those previous studies (total n = 2013 donors), identifying 334 cortical differentially methylated positions (DMPs) associated pathology...
LSH, a member of the SNF2 family chromatin remodeling ATPases encoded by Hells gene, is essential for normal levels DNA methylation in mammalian genome. While role LSH repetitive sequences well characterized, its contribution to regulation and expression protein-coding genes has not been studied detail. In this report we investigate genome-wide patterns at gene promoters −/− mouse embryonic fibroblasts (MEFs). We find that absence lost or significantly reduced ∼20% all normally methylated...
Major depressive disorder (MDD) represents a major social and economic health issue constitutes risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the both MDD suicidality. In this study, genome-wide patterns DNA methylation were assessed depressed suicide completers (n=20) compared with non-psychiatric, sudden-death controls using tissue from two cortical brain...
Aim: The present study investigated the link between peripheral DNA methylation (DNAm), cognitive impairment and brain aging. Methods: We tested association blood genome-wide DNAm profiles using Illumina 450K arrays, dysfunction MRI measures in selected participants of Whitehall II imaging sub-study. Results: Eight differentially methylated regions were associated with impairment. Accelerated aging based on Hannum epigenetic clock was mean diffusivity global fractional anisotropy. also...
The datasets generated by DNA methylation analyses are getting bigger. With the release of HumanMethylationEPIC micro-array and containing thousands samples, these large using R becoming impractical due to memory requirements. As a result there is an increasing need for computationally efficient methodologies perform meaningful analysis on high dimensional data.Here we introduce bigmelon package, which provides workflow that enables users complex, scale required in epigenome wide association...
Most epigenome-wide association studies (EWAS) quantify DNA methylation (DNAm) in peripheral tissues such as whole blood to identify positions the genome where variation is statistically associated with a trait or exposure. As comprises mix of cell types, it unclear whether trait-associated DNAm specific an individual cellular population. We collected three (whole blood, buccal epithelial and nasal cells) from thirty individuals. Whole samples were subsequently processed using...
Due to interindividual variation in the cellular composition of human cortex, it is essential that covariates capture these differences are included epigenome-wide association studies using bulk tissue. As experimentally derived cell counts often unavailable, computational solutions have been adopted estimate proportion different types DNA methylation data. Here, we validate and profile use an expanded reference dataset incorporating two neuronal three glial subtypes for quantifying cortex.
LSH, a protein related to the SNF2 family of chromatin-remodelling ATPases, is essential for correct establishment DNA methylation levels and patterns in plants mammalian cells. However, some phenotypes resulting from LSH deficiency cannot be explained easily by defects methylation. Here we show that LSH-deficient mouse human fibroblasts reduced viability after exposure ionizing radiation repair double-strand breaks less efficiently than wild-type A more detailed characterisation this...
The age profile of populations fundamentally affects their conservation status. Yet, is frequently difficult to assess in wild animals. Here, we assessed the use DNA methylation homologous genes establish structure a rare and elusive mammal: Bechstein's bat (Myotis bechsteinii). We collected 62 wing punches from individuals whose ages were known as result long-term banding study. was measured at seven CpG sites three genes, which have previously shown age-associated changes humans laboratory...