scholarly journals The EWAS Catalog: a database of epigenome-wide association studies

2021 ◽  
Author(s):  
Thomas Battram ◽  
Paul Yousefi ◽  
Gemma Crawford ◽  
Claire Prince ◽  
Mahsa Sheikhali Babei ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Association Studies ◽  
R Package ◽  
Population Based ◽  
Case Control Studies ◽  
Web Based ◽  
Parents And Children ◽  
The Impact ◽  
Avon Longitudinal Study ◽  
Insight Into

Epigenome-wide association studies (EWAS) seek to quantify associations between traits/exposures and DNA methylation measured at thousands or millions of CpG sites across the genome. In recent years, the increase in availability of DNA methylation measures in population-based cohorts and case-control studies has resulted in a dramatic expansion of the number of EWAS being performed and pub-lished. To make this rich source of results more accessible, we have manually curated a database of CpG-trait associations (with p<1x10-4) from published EWAS, each assaying over 100,000 CpGs in at least 100 individuals. From 2021-01-29, The EWAS Catalog contained 1,045,303 associations from over 1000 EWAS. This includes 652,530 associations from 264 peer-reviewed publications. In addi-tion, it also contains summary statistics for 392,773 associations from 428 EWAS, performed in data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Gene Expression Om-nibus (GEO). The database is accompanied by a web-based tool and R package, giving researchers the opportunity to quickly and easily query EWAS associations and gain insight into the molecular under-pinnings of disease as well as the impact of traits and exposures on the DNA methylome. The EWAS Catalog is available at: http://www.ewascatalog.org.

scholarly journals The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Generation 2 questionnaire data capture May-July 2020

2021 ◽  
Vol 5 ◽  
pp. 278
Author(s):  
Daniel Smith ◽  
Kate Northstone ◽  
Claire Bowring ◽  
Nicholas Wells ◽  
Michael Crawford ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
School Attendance ◽  
Population Based ◽  
Children's Health ◽  
Children’S Health ◽  
Questionnaire Data ◽  
Contact Patterns ◽  
Parents And Children ◽  
The Impact ◽  
Avon Longitudinal Study

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 from the Bristol area (UK). ALSPAC has followed these women, their partners (Generation 0; G0) and their offspring (Generation 1; G1) ever since. From 2012, ALSPAC has identified G1 participants who were pregnant (or their partner was) or had become parents, and enrolled them, their partners, and children in the ALSPAC-Generation 2 (ALSPAC-G2) study, providing a unique multi-generational cohort. At present, approximately 1,100 G2 children (excluding those in utero) from 810 G1 participants have been enrolled. In response to the COVID-19 pandemic, ALSPAC rapidly deployed two online questionnaires; one during the initial lockdown phase in 2020 (9th April-15th May), and another when national lockdown restrictions were eased (26th May-5th July). As part of this second questionnaire, G1 parents completed a questionnaire about each of their G2 children. This covered: parental reports of children’s feelings and behaviour since lockdown, school attendance, contact patterns, and health. A total of 289 G1 participants completed this questionnaire on behalf of 411 G2 children. This COVID-19 G2 questionnaire data can be combined with pre-pandemic ALSPAC-G2 data, plus ALSPAC-G1 and -G0 data, to understand how children’s health and behaviour has been affected by the pandemic and its management. Data from this questionnaire will be complemented with linkage to health records and results of biological testing as they become available. Prospective studies are necessary to understand the impact of this pandemic on children’s health and development, yet few relevant studies exist; this resource will aid these efforts. Data has been released as: 1) a freely-available dataset containing participant responses with key sociodemographic variables; and 2) an ALSPAC-held dataset which can be combined with existing ALSPAC data, enabling bespoke research across all areas supported by the study.

scholarly journals The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Questionnaire data capture April-May 2020

2020 ◽  
Vol 5 ◽  
pp. 127 ◽  
Author(s):  
Kate Northstone ◽  
Simown Howarth ◽  
Daniel Smith ◽  
Claire Bowring ◽  
Nicholas Wells ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Sociodemographic Factors ◽  
Population Based ◽  
Online Questionnaire ◽  
Health Records ◽  
Parents And Children ◽  
Seasonal Flu ◽  
The Impact ◽  
Avon Longitudinal Study

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992. The resource provides an informative and efficient setting for collecting data on the current coronavirus 2019 (COVID-19) pandemic. In early March 2020, a questionnaire was developed in collaboration with other longitudinal population studies to ensure cross-cohort comparability. It targeted retrospective and current COVID-19 infection information (exposure assessment, symptom tracking and reported clinical outcomes) and the impact of both disease and mitigating measures implemented to manage the COVID-19 crisis more broadly. Data were collected on symptoms of COVID-19 and seasonal flu, travel prior to the pandemic, mental health and social, behavioural and lifestyle factors. The online questionnaire was deployed across the parent and offspring generations between the 9th April and 15th May 2020. 6807 participants completed the questionnaire (2706 original mothers, 1014 original fathers/partners, 2973 offspring (mean age ~28 years) and 114 partners of offspring). Eight (0.01%) participants (4 G0 and 4 G1) reported a positive test for COVID-19, 77 (1.13%; 28 G0 and 49 G1) reported that they had been told by a doctor they likely had COVID-19 and 865 (12.7%; 426 G0 and 439 G1) suspected that they have had COVID-19.  Using algorithmically defined cases, we estimate that the predicted proportion of COVID-19 cases fell between 1.03% - 4.19% depending on timing of measurement during the period of reporting. Data from this first questionnaire will be complemented with at least two more follow-up questionnaires, linkage to health records and results of biological testing as they become available. Data has been released as: 1) a standard dataset containing all participant responses with key sociodemographic factors and 2) as a composite release coordinating data from the existing resource, thus enabling bespoke research across all areas supported by the study.

scholarly journals Updates to data versions and analytic methods influence the reproducibility of results from epigenome-wide association studies

2021 ◽  
Author(s):  
Alexandre A. Lussier ◽  
Yiwen Zhu ◽  
Brooke J. Smith ◽  
Andrew J. Simpkin ◽  
Andrew D.A.C. Smith ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Association Studies ◽  
Childhood Adversity ◽  
Reference Points ◽  
Time Dependent ◽  
P Value ◽  
Prenatal Smoking ◽  
Parents And Children ◽  
Successful Replication ◽  
The Impact

ABSTRACTIntroductionBiomedical research has grown increasingly cooperative, with several large consortia compiling and sharing epigenomic data. Since data are typically preprocessed by consortia prior to distribution, the implementation of new pipelines can lead to different versions of the same dataset. Analytic frameworks also constantly evolve to incorporate cutting-edge methods and shifting best practices. However, it remains unknown how differences in data and analytic versions alter the results of epigenome-wide analyses, which has broad implications for the replicability of epigenetic associations. Thus, we assessed the impact of these changes using a subsample of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.MethodsWe analyzed two versions of DNA methylation data, processed using separate preprocessing and analytic pipelines, to examine associations between childhood adversity and prenatal smoking exposure on DNA methylation at age 7. We performed two sets of analyses: (1) epigenome-wide association studies (EWAS); (2) Structured Life Course Modeling Approach (SLCMA), a two-stage method that models time-dependent effects. We also compared results from the SLCMA using more recent methodological recommendations.ResultsDifferences between ALSPAC data versions impacted both EWAS and SLCMA analyses, yielding different sets of associations at conventional p-value thresholds. However, the magnitude and direction of associations was generally consistent between data versions, regardless of significance thresholds. Updating the SLCMA analytic version similarly altered top associations, but time-dependent effects remained concordant.ConclusionsChanges to data and analytic versions influenced the results of epigenome-wide studies, particularly when using p-value thresholds as reference points for successful replication and stability.

scholarly journals The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Generation 2 questionnaire data capture May-July 2020

2020 ◽  
Vol 5 ◽  
pp. 278
Author(s):  
Daniel Smith ◽  
Kate Northstone ◽  
Claire Bowring ◽  
Nicholas Wells ◽  
Michael Crawford ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
School Attendance ◽  
Population Based ◽  
Children's Health ◽  
Children’S Health ◽  
Questionnaire Data ◽  
Contact Patterns ◽  
Parents And Children ◽  
The Impact ◽  
Avon Longitudinal Study

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 from the Bristol area (UK). ALSPAC has followed these women, their partners (Generation 0; G0) and their offspring (Generation 1; G1) ever since. From 2012, ALSPAC has identified G1 participants who were pregnant (or their partner was) or had become parents, and enrolled them, their partners, and children in the ALSPAC-Generation 2 (ALSPAC-G2) study, providing a unique multi-generational cohort. At present, approximately 1,100 G2 children (excluding those in utero) from 810 G1 participants have been enrolled. In response to the COVID-19 pandemic, ALSPAC rapidly deployed two online questionnaires; one during the initial lockdown phase in 2020 (9th April-15th May), and another when national lockdown restrictions were eased (26th May-5th July). As part of this second questionnaire, G1 parents completed a questionnaire about each of their G2 children. This covered: parental reports of children’s feelings and behaviour since lockdown, school attendance, contact patterns, and health. A total of 289 G1 participants completed this questionnaire on behalf of 411 G2 children. This COVID-19 G2 questionnaire data can be combined with pre-pandemic ALSPAC-G2 data, plus ALSPAC-G1 and -G0 data, to understand how children’s health and behaviour has been affected by the pandemic and its management. Data from this questionnaire will be complemented with linkage to health records and results of biological testing as they become available. Prospective studies are necessary to understand the impact of this pandemic on children’s health and development, yet few relevant studies exist; this resource will aid these efforts. Data has been released as: 1) a freely-available dataset containing participant responses with key sociodemographic variables; and 2) an ALSPAC-held dataset which can be combined with existing ALSPAC data, enabling bespoke research across all areas supported by the study.

scholarly journals The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Questionnaire data capture April-May 2020

2020 ◽  
Vol 5 ◽  
pp. 127 ◽  
Author(s):  
Kate Northstone ◽  
Simown Howarth ◽  
Daniel Smith ◽  
Claire Bowring ◽  
Nicholas Wells ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Sociodemographic Factors ◽  
Population Based ◽  
Online Questionnaire ◽  
Health Records ◽  
Parents And Children ◽  
Seasonal Flu ◽  
The Impact ◽  
Avon Longitudinal Study

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992. The resource provides an informative and efficient setting for collecting data on the current coronavirus 2019 (COVID-19) pandemic. In early March 2020, a questionnaire was developed in collaboration with other longitudinal population studies to ensure cross-cohort comparability. It targeted retrospective and current COVID-19 infection information (exposure assessment, symptom tracking and reported clinical outcomes) and the impact of both disease and mitigating measures implemented to manage the COVID-19 crisis more broadly. Data were collected on symptoms of COVID-19 and seasonal flu, travel prior to the pandemic, mental health and social, behavioural and lifestyle factors. The online questionnaire was deployed across parent (G0) and offspring (G1) generations between 9th April and 15th May 2020. 6807 participants completed the questionnaire (2706 original mothers, 1014 original fathers/partners, 2973 offspring (mean age ~28 years) and 114 offspring partners). Eight (0.01%) participants (4 G0 and 4 G1) reported a positive test for COVID-19, 77 (1.13%; 28 G0 and 49 G1) reported that they had been told by a doctor they likely had COVID-19 and 865 (12.7%; 426 G0 and 439 G1) suspected that they have had COVID-19.  Using algorithmically defined cases, we estimate that the predicted proportion of COVID-19 cases ranged from 1.03% - 4.19% depending on timing during the period of reporting (October 2019-March 2020). Data from this first questionnaire will be complemented with at least two more follow-up questionnaires, linkage to health records and results of biological testing as they become available. Data has been released as: 1) a standard dataset containing all participant responses with key sociodemographic factors and 2) as a composite release coordinating data from the existing resource, thus enabling bespoke research across all areas supported by the study.

scholarly journals Epigenome-wide associations between observed maternal sensitivity and offspring DNA methylation: a population-based prospective study in children

2020 ◽  
pp. 1-11
Author(s):  
Lorenza Dall’ Aglio ◽  
Jolien Rijlaarsdam ◽  
Rosa H. Mulder ◽  
Alexander Neumann ◽  
Janine F. Felix ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stress Responses ◽  
Association Studies ◽  
Maternal Sensitivity ◽  
Population Based ◽  
Epigenetic Mechanism ◽  
Developmental Problems ◽  
Maternal Caregiving ◽  
Typical Variation

Abstract Background Experimental work in animals has shown that DNA methylation (DNAm), an epigenetic mechanism regulating gene expression, is influenced by typical variation in maternal care. While emerging research in humans supports a similar association, studies to date have been limited to candidate gene and cross-sectional approaches, with a focus on extreme deviations in the caregiving environment. Methods Here, we explored the prospective association between typical variation in maternal sensitivity and offspring epigenome-wide DNAm, in a population-based cohort of children (N = 235). Maternal sensitivity was observed when children were 3- and 4-years-old. DNAm, quantified with the Infinium 450 K array, was extracted at age 6 (whole blood). The influence of methylation quantitative trait loci (mQTLs), DNAm at birth (cord blood), and confounders (socioeconomic status, maternal psychopathology) was considered in follow-up analyses. Results Genome-wide significant associations between maternal sensitivity and offspring DNAm were observed at 13 regions (p < 1.06 × 10−07), but not at single sites. Follow-up analyses indicated that associations at these regions were in part related to genetic factors, confounders, and baseline DNAm levels at birth, as evidenced by the presence of mQTLs at five regions and estimate attenuations. Robust associations with maternal sensitivity were found at four regions, annotated to ZBTB22, TAPBP, ZBTB12, and DOCK4. Conclusions These findings provide novel leads into the relationship between typical variation in maternal caregiving and offspring DNAm in humans, highlighting robust regions of associations, previously implicated in psychological and developmental problems, immune functioning, and stress responses.

scholarly journals Ewastools: Infinium Human Methylation BeadChip pipeline for population epigenetics integrated into Galaxy

GigaScience ◽  
2020 ◽  
Vol 9 (5) ◽  
Author(s):  
Katarzyna Murat ◽  
Björn Grüning ◽  
Paulina Wiktoria Poterlowicz ◽  
Gillian Westgate ◽  
Desmond J Tobin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Association Studies ◽  
Methylation Analysis ◽  
Web Based ◽  
Array Platform ◽  
Complex Evaluation ◽  
The Galaxy ◽  
Population Epigenetics ◽  
Analyse Data ◽  
Dna Methylation Analysis

Abstract Background Infinium Human Methylation BeadChip is an array platform for complex evaluation of DNA methylation at an individual CpG locus in the human genome based on Illumina’s bead technology and is one of the most common techniques used in epigenome-wide association studies. Finding associations between epigenetic variation and phenotype is a significant challenge in biomedical research. The newest version, HumanMethylationEPIC, quantifies the DNA methylation level of 850,000 CpG sites, while the previous versions, HumanMethylation450 and HumanMethylation27, measured &gt;450,000 and 27,000 loci, respectively. Although a number of bioinformatics tools have been developed to analyse this assay, they require some programming skills and experience in order to be usable. Results We have developed a pipeline for the Galaxy platform for those without experience aimed at DNA methylation analysis using the Infinium Human Methylation BeadChip. Our tool is integrated into Galaxy (http://galaxyproject.org), a web-based platform. This allows users to analyse data from the Infinium Human Methylation BeadChip in the easiest possible way. Conclusions The pipeline provides a group of integrated analytical methods wrapped into an easy-to-use interface. Our tool is available from the Galaxy ToolShed, GitHub repository, and also as a Docker image. The aim of this project is to make Infinium Human Methylation BeadChip analysis more flexible and accessible to everyone.

scholarly journals Meffil: efficient normalisation and analysis of very large DNA methylation samples

2017 ◽  
Author(s):  
Josine Min ◽  
Gibran Hemani ◽  
George Davey Smith ◽  
Caroline Relton ◽  
Matthew Suderman
Keyword(s):  
Dna Methylation ◽  
Association Studies ◽  
R Package ◽  
Individual Level ◽  
Technological Advances ◽  
Level Data ◽  
Fixed And Random Effects ◽  
R Packages ◽  
Meta Analyses ◽  
Dramatic Growth

AbstractBackgroundTechnological advances in high throughput DNA methylation microarrays have allowed dramatic growth of a new branch of epigenetic epidemiology. DNA methylation datasets are growing ever larger in terms of the number of samples profiled, the extent of genome coverage, and the number of studies being meta-analysed. Novel computational solutions are required to efficiently handle these data.MethodsWe have developed meffil, an R package designed to quality control, normalize and perform epigenome-wide association studies (EWAS) efficiently on large samples of Illumina Infinium HumanMethylation450 and MethylationEPIC BeadChip microarrays. We tested meffil by applying it to 6000 450k microarrays generated from blood collected for two different datasets, Accessible Resource for Integrative Epigenomic Studies (ARIES) and The Genetics of Overweight Young Adults (GOYA) study.ResultsA complete reimplementation of functional normalization minimizes computational memory requirements to 5% of that required by other R packages, without increasing running time. Incorporating fixed and random effects alongside functional normalization, and automated estimation of functional normalisation parameters reduces technical variation in DNA methylation levels, thus reducing false positive associations and improving power. We also demonstrate that the ability to normalize datasets distributed across physically different locations without sharing any biologically-based individual-level data may reduce heterogeneity in meta-analyses of epigenome-wide association studies. However, we show that when batch is perfectly confounded with cases and controls functional normalization is unable to prevent spurious associations.Conclusionsmeffil is available online (https://github.com/perishky/meffil/) along with tutorials covering typical use cases.

scholarly journals Have associations between mental health and health related behaviours changed between 2005 and 2015? A population based cross-cohort study

2020 ◽  
Author(s):  
Suzanne H. Gage ◽  
Praveetha Patalay
Keyword(s):  
Mental Health ◽  
Substance Use ◽  
Cohort Study ◽  
Mental Health Problems ◽  
Weight Perception ◽  
Population Based ◽  
Parents And Children ◽  
Health Related ◽  
Avon Longitudinal Study ◽  
Over Time

AbstractBackgroundPoor adolescent mental health is a growing concern over recent decades with evidence of increasing internalising mental health problems corresponding with decrease in anti-social, smoking and alcohol behaviours. However, understanding whether and how the associations between mental health and health-related behaviours such as substance use, anti-social behaviour and obesity have changed over time is less well-understood.ObjectivesWe investigate whether the associations between different health-related outcomes in adolescence are stable or changing over time in two recent cohorts of adolescents born ten years apart.MethodData from two UK birth cohort studies, the Avon Longitudinal Study of Parents and Children (ALSPAC, born 1991-92, N=5627, 50.7% female) and Millennium Cohort Study (MCS, born 2000-1, N=11318, 50.6% female) at age 14 sweeps are used. The health outcomes of focus are depressive symptom score, substance use (alcohol, smoking, cannabis and other drugs), antisocial behaviours (assault, graffiti, vandalism, shoplifting and rowdy behaviour), weight (BMI), weight perception (perceive self as overweight) and sexual activity (had sexual intercourse).ResultsOur results suggest although directions of associations between mental-health and health-related behaviours (eg smoking) are similar over time, their strength across the distribution has changed. While smoking and alcohol use behaviours are decreasing in adolescents, those that endorse these behaviours in 2015 are more likely to have co-occurring mental-health and other problems than those born in 2005. Similarly, higher body mass index is more strongly associated with depressive symptoms in 2015.ConclusionsOur findings suggest that associations between these factors has changed over time, which has implications for public health and our understanding of the mechanisms underlying their observed associations in the population.

scholarly journals Epigenome-wide association study of seizures in childhood and adolescence

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Doretta Caramaschi ◽  
Charlie Hatcher ◽  
Rosa H. Mulder ◽  
Janine F. Felix ◽  
Charlotte A. M. Cecil ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Independent Study ◽  
Childhood And Adolescence ◽  
Parents And Children ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
The Brain ◽  
Avon Longitudinal Study

AbstractThe occurrence of seizures in childhood is often associated with neurodevelopmental impairments and school underachievement. Common genetic variants associated with epilepsy have been identified and epigenetic mechanisms have also been suggested to play a role. In this study, we analyzed the association of genome-wide blood DNA methylation with the occurrence of seizures in ~ 800 children from the Avon Longitudinal Study of Parents and Children, UK, at birth (cord blood), during childhood, and adolescence (peripheral blood). We also analyzed the association between the lifetime occurrence of any seizures before age 13 with blood DNA methylation levels. We sought replication of the findings in the Generation R Study and explored causality using Mendelian randomization, i.e., using genetic variants as proxies. The results showed five CpG sites which were associated cross-sectionally with seizures either in childhood or adolescence (1–5% absolute methylation difference at pFDR < 0.05), although the evidence of replication in an independent study was weak. One of these sites was located in the BDNF gene, which is highly expressed in the brain, and showed high correspondence with brain methylation levels. The Mendelian randomization analyses suggested that seizures might be causal for changes in methylation rather than vice-versa. In conclusion, we show a suggestive link between seizures and blood DNA methylation while at the same time exploring the limitations of conducting such study.

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