A5042511675- Epigenetics and DNA Methylation
- Birth, Development, and Health
- Health, Environment, Cognitive Aging
- Genetic Associations and Epidemiology
- Folate and B Vitamins Research
- RNA modifications and cancer
- Neonatal Respiratory Health Research
- Gestational Diabetes Research and Management
- Childhood Cancer Survivors' Quality of Life
- Genetic Syndromes and Imprinting
- Pregnancy and preeclampsia studies
- Cancer-related molecular mechanisms research
- Nutritional Studies and Diet
- Obesity, Physical Activity, Diet
- Adolescent and Pediatric Healthcare
- Tryptophan and brain disorders
- Nutrition, Genetics, and Disease
- Smoking Behavior and Cessation
- Asthma and respiratory diseases
- Bioinformatics and Genomic Networks
- COVID-19 and Mental Health
- Cancer-related gene regulation
- Cleft Lip and Palate Research
- COVID-19 epidemiological studies
- Genetic and phenotypic traits in livestock
MRC Epidemiology Unit
2015-2024
University of Bristol
2015-2024
London School of Hygiene & Tropical Medicine
2012-2024
NIHR Bristol Biomedical Research Centre
2018-2024
Manufacturas Serviplast (Spain)
2024
Institut Català d'Oncologia
2024
Newcastle University
2012-2023
University Hospitals Bristol NHS Foundation Trust
2018-2023
National Institute for Health Research
2018-2023
University College London
2012-2023
Results from genome-wide association studies (GWAS) can be used to infer causal relationships between phenotypes, using a strategy known as 2-sample Mendelian randomization (2SMR) and bypassing the need for individual-level data. However, 2SMR methods are evolving rapidly GWAS results often insufficiently curated, undermining efficient implementation of approach. We therefore developed MR-Base ( http://www.mrbase.org ): platform that integrates curated database complete (no restrictions...
<ns4:p>This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, journal editors reviewers assess manuscripts. The are divided into nine sections: motivation scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary sensitivity (one section on robust methods one other approaches), presentation, interpretation. These will be updated...
<ns4:p>This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, journal editors reviewers assess manuscripts. The are divided into nine sections: motivation scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary sensitivity (one section on robust statistical methods one other approaches), presentation, interpretation. These will...
Background Assessing the relationship between lung cancer and metabolic conditions is challenging because of confounding effect tobacco. Mendelian randomization (MR), or use genetic instrumental variables to assess causality, may help identify drivers cancer. Methods findings We identified instruments for potential risk factors evaluated these in relation using 29,266 cases (including 11,273 adenocarcinomas, 7,426 squamous cell 2,664 small cases) 56,450 controls. The MR analysis suggested a...
Mitochondrial DNA (mtDNA) mutations are a major cause of genetic disease, but their prevalence in the general population is not known. We determined frequency ten mitochondrial point 3168 neonatal-cord-blood samples from sequential live births, analyzing matched maternal-blood to estimate de novo mutation rate. mtDNA were detected 15 offspring (0.54%, 95% CI = 0.30–0.89%). Of these 0.00107% (95% 0.00087–0.0127) harbored mother's blood, providing an The most common was m.3243A→G. m.14484T→C...
The influence of genetic variation on complex diseases is potentially mediated through a range highly dynamic epigenetic processes exhibiting temporal during development and later life. Here we present catalogue the influences DNA methylation (methylation quantitative trait loci (mQTL)) at five different life stages in human blood: children birth, childhood, adolescence their mothers pregnancy middle age. We show that effects are stable across course developmental change contribution to...
Mendelian randomization (MR) is an increasingly important tool for appraising causality in observational epidemiology. The technique exploits the principle that genotypes are not generally susceptible to reverse causation bias and confounding, reflecting their fixed nature Mendel’s first second laws of inheritance. approach is, however, subject limitations assumptions that, if unaddressed or compounded by poor study design, can lead erroneous conclusions. Nevertheless, advent 2-sample...
The burgeoning interest in the field of epigenetics has precipitated need to develop approaches strengthen causal inference when considering role epigenetic mediators environmental exposures on disease risk. Epigenetic markers, like any other molecular biomarker, are vulnerable confounding and reverse causation. Here, we present a strategy, based well-established framework Mendelian randomization, interrogate relationships between exposure, DNA methylation outcome. two-step approach first...
Maternal smoking during pregnancy has been found to influence newborn DNA methylation in genes involved fundamental developmental processes. It is pertinent understand the degree which offspring methylome sensitive intensity and duration of prenatal smoking. An investigation persistence associated with maternal relative roles intrauterine postnatal environment also warranted. In Avon Longitudinal Study Parents Children, we investigated associations between exposure at multiple time points...
<ns3:p>This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, journal editors reviewers assess manuscripts. The are divided into ten sections: motivation scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary sensitivity (one section on robust statistical methods one other approaches), extensions additional analyses,...
Data Resource Profile: Accessible for Integrated Epigenomic Studies (ARIES) Caroline L Relton, Tom Gaunt, Wendy McArdle, Karen Ho, Aparna Duggirala, Hashem Shihab, Geoff Woodward, Oliver Lyttleton, David M Evans, Wolf Reik, Yu-Lee Paul, Gabriella Ficz, Susan E Ozanne, Anil Wipat, Keith Flanagan, Allyson Lister, Bastiaan T Heijmans, Ring and George Davey Smith MRC Integrative Epidemiology Unit, School of Social Community Medicine, University Bristol, UK, Institute Genetic Newcastle...
DNA methylation datasets are growing ever larger both in sample size and genome coverage. Novel computational solutions required to efficiently handle these data.We have developed meffil, an R package designed for efficient quality control, normalization epigenome-wide association studies of large samples Illumina Methylation BeadChip microarrays. A complete re-implementation functional minimizes memory without increasing running time. Incorporating fixed random effects within normalization,...
DNA methylation is strongly associated with smoking status at multiple sites across the genome. Studies have largely been restricted to European origin individuals yet greatest increase in occurring low income countries, such as Indian subcontinent. We determined whether there are differences between South Asians and Europeans related loci, if a score, combining all scores, could differentiate smokers from non-smokers. Illumina HM450k BeadChip arrays were performed on 192 samples Southall...
Background: Evidence suggests that in utero exposure to undernutrition and overnutrition might affect adiposity later life. Epigenetic modification is suggested as a plausible mediating mechanism. Methods: We used multivariable linear regression negative control design examine offspring epigenome-wide DNA methylation relation maternal 1018 participants. Results: Compared with neonatal of normal weight mothers, 28 1621 CpG sites were differentially methylated obese underweight respectively...
DNA methylation-based biomarkers of aging are highly correlated with actual age. Departures methylation-estimated age from can be used to define epigenetic measures child development or acceleration (AA) in adults. Very little is known about genetic environmental determinants these aging. We obtained methylation profiles using Infinium HumanMethylation450 BeadChips across five time-points 1018 mother–child pairs the Avon Longitudinal Study Parents and Children. Using Horvath estimation...
Abstract DNA hypomethylation in certain genes is associated with tobacco exposure but it unknown whether these methylation changes translate into increased lung cancer risk. In an epigenome-wide study of from pre-diagnostic blood samples 132 case–control pairs the NOWAC cohort, we observe that most significant associations risk are for cg05575921 AHRR (OR 1 s.d.=0.37, 95% CI: 0.31–0.54, P -value=3.3 × 10 −11 ) and cg03636183 F2RL3 s.d.=0.40, 0.31–0.56, -value=3.9 −10 ), previously shown to...