scholarly journals Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time

Epigenetics ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. 19-32 ◽  
Author(s):  
Marie Forest ◽  
Kieran J. O'Donnell ◽  
Greg Voisin ◽  
Helene Gaudreau ◽  
Julia L. MacIsaac ◽  
...  
Keyword(s):  
Dna Methylation ◽  
450K Array ◽  
Illumina 450K ◽  
Illumina 450K Array

scholarly journals Apolipoprotein E DNA methylation and late-life disease

2018 ◽  
Vol 47 (3) ◽  
pp. 899-907 ◽  
Author(s):  
Ida K Karlsson ◽  
Alexander Ploner ◽  
Yunzhang Wang ◽  
Margaret Gatz ◽  
Nancy L Pedersen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Apolipoprotein E ◽  
Promoter Region ◽  
Allelic Variation ◽  
450K Array ◽  
Blood Draw ◽  
Standard Deviation Increase ◽  
Illumina 450K ◽  
Apoe Locus ◽  
Illumina 450K Array

Abstract Background This study aims to investigate if DNA methylation of the apolipoprotein E (APOE) locus affects the risks of dementia, Alzheimeŕs disease (AD) or cardiovascular disease (CVD). Methods DNA methylation across theAPOE gene has previously been categorized into three distinct regions: a hypermethylated region in the promoter, a hypomethylated region in the first two introns and exons and a hypermethylated region in the 3′exon that also harbours theAPOE ε2 and ε4 alleles. DNA methylation levels in leukocytes were measured using the Illumina 450K array in 447 Swedish twins (mean age 78.1 years). We used logistic regression to investigate whether methylation levels in those regions affect the odds of disease. Results We found that methylation levels in the promoter region were associated with dementia and AD after adjusting for sex, age at blood draw, education, smoking and relatedness among twins [odds ratio (OR) 1.32 per standard deviation increase in methylation levels, 95% confidence interval (CI) 1.08–1.62 for dementia; OR 1.38, 95% CI 1.07–1.78 for AD). We did not detect any difference in methylation levels between CVD cases and controls. Results were similar when comparing within discordant twin pairs, and did not differ as a function ofAPOE genotype. Conclusions We found that higher DNA methylation levels in the promoter region ofAPOE increase the odds of dementia and AD, but not CVD. The effect was independent ofAPOE genotype, indicating that allelic variation and methylation variation inAPOE may act independently to increase the risk of dementia.

scholarly journals Integrative analysis with expanded DNA methylation data reveals common key regulators and pathways in cancers

2018 ◽  
Author(s):  
Shicai Fan ◽  
Jianxiong Tang ◽  
Nan Li ◽  
Ying Zhao ◽  
Rizi Ai ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Therapeutic Targets ◽  
Integrative Analysis ◽  
Axonal Guidance ◽  
Methylation Data ◽  
450K Array ◽  
Diagnosis And Prognosis ◽  
Illumina 450K ◽  
Illumina 450K Array

AbstractThe integration of genomic and DNA methylation data has been demonstrated as a powerful strategy in understanding cancer mechanisms and identifying therapeutic targets. The TCGA consortium has mapped DNA methylation in thousands of cancer samples using Illumina Infinium Human Methylation 450K BeadChip (Illumina 450K array) that only covers about 1.5% of CpGs in the human genome. Therefore, increasing the coverage of the DNA methylome would significantly leverage the usage of the TCGA data. Here, we present a new model called EAGLING that can expand the Illumina 450K array data 18 times to cover about 30% of the CpGs in the human genome. We applied it to analyze 13 cancers in TCGA. By integrating the expanded methylation, gene expression and somatic mutation data, we identified the genes showing differential patterns in each of the 13 cancers. Many of the triple-evidenced genes identified in the majority of the cancers are biomarkers or potential biomarkers. Pan-cancer analysis also revealed the pathways in which the triple-evidenced genes are enriched, which include well known ones as well as new ones such as axonal guidance signaling pathway and pathways related to inflammatory processing or inflammation response. Triple-evidenced genes, particularly TNXB, RRM2, CELSR3, SLC16A3, FANCI, MMP9, MMP11, SIK1, TRIM59, showed superior predictive power in both tumor diagnosis and prognosis. These results have demonstrated that the integrative analysis using the expanded methylation data is powerful in identifying critical genes/pathways that may serve as new therapeutic targets.

scholarly journals Identification and systematic annotation of tissue-specific differentially methylated regions using the Illumina 450k array

2013 ◽  
Vol 6 (1) ◽  
pp. 26 ◽  
Author(s):  
Roderick C Slieker ◽  
Steffan D Bos ◽  
Jelle J Goeman ◽  
Judith VMG Bovée ◽  
Rudolf P Talens ◽  
...  
Keyword(s):  
Differentially Methylated Regions ◽  
450K Array ◽  
Tissue Specific ◽  
Illumina 450K ◽  
Illumina 450K Array

scholarly journals Maternal blood metal concentrations and whole blood DNA methylation during pregnancy in the Early Autism Risk Longitudinal Investigation (EARLI)

2020 ◽  
Author(s):  
Max T. Aung ◽  
Kelly M. Bakulski ◽  
Jason I. Feinberg ◽  
John F. Dou ◽  
John D. Meeker ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Linear Regression ◽  
Whole Blood ◽  
Maternal Blood ◽  
Nervous System Development ◽  
Q Value ◽  
450K Array ◽  
Smoking During Pregnancy ◽  
Longitudinal Investigation ◽  
Cadmium Lead

AbstractBackgroundMetals exposures have important health effects in pregnancy. The maternal epigenome may be responsive to these exposures. We tested whether metals are associated with concurrent differential maternal whole blood DNA methylation.MethodsIn the Early Autism Risk Longitudinal Investigation (EARLI) cohort, we measured first or second trimester maternal blood metals concentrations (cadmium, lead, mercury, manganese, and selenium) in 215 participants using inductively coupled plasma mass spectrometry. DNA methylation in maternal whole blood was measured in the same specimens on the Illumina 450K array (201 participants). A subset sample of 97 women had both measures available for analysis, all of whom did not report smoking during pregnancy. Linear regression was used to test for site-specific associations between individual metals and DNA methylation, adjusting for cell type composition and confounding variables. Discovery gene ontology analysis was conducted on the top 1,000 sites associated with each metal to elucidate downstream pathways.ResultsIn multiple linear regression, we observed hypermethylation at 11 DNA methylation sites associated with lead (FDR q-value <0.1), near the genes CYP24A1, ASCL2, FAT1, SNX31, NKX6-2, LRC4C, BMP7, HOXC11, PCDH7, ZSCAN18, and VIPR2. Lead associated sites were enriched (FDR q-value <0.1) for the pathways cell adhesion, nervous system development, and calcium ion binding. Manganese was associated with hypermethylation at four DNA methylation sites (FDR q-value <0.1), one of which was near the gene ARID2. Manganese associated sites were enriched for cellular metabolism pathways (FDR q-value<0.1). Effect estimates for DNA methylation sites associated (p<0.05) with cadmium, lead, and manganese were highly correlated (Pearson ρ >0.86).DiscussionSingle DNA methylation sites associated with lead and manganese may be potential biomarkers of exposure or implicate downstream gene pathways. Future studies should replicate our findings to characterize potential toxicological mechanisms of trace metals through the maternal epigenome.

scholarly journals Derivation of Poly-Methylomic Profile Scores for Schizophrenia

2019 ◽  
Author(s):  
Oliver J. Watkeys ◽  
Sarah Cohen-Woods ◽  
Yann Quidé ◽  
Murray J. Cairns ◽  
Bronwyn Overs ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Multiple Testing ◽  
P Value ◽  
Summary Statistics ◽  
Illumina 450K ◽  
Profile Score ◽  
Methylation Patterns ◽  
Control Association ◽  
Schizophrenia Case ◽  
450K Methylation

AbstractSchizophrenia (SZ) and bipolar disorder (BD) share numerous clinical and biological features as well as environmental risk factors that may be associated with altered DNA methylation. In this study we sought to construct a Poly-Methylomic Profile Score (PMPS) for SZ, representing the degree of epigenome-wide methylation according to previously published findings; we then examined its association with SZ and BD in an independent sample. DNA methylation for 57 SZ, 59 BD cases and 55 healthy controls (HCs) was quantified using the Illumina 450K methylation beadchip. We constructed five PMPSs for different p-value thresholds using summary statistics reported in a large epigenome-wide schizophrenia case-control association study, weighted by individual CpG effect sizes. All SZ PMPSs were significantly elevated in SZ cases relative to HCs, with the score calculated at the most stringent threshold accounting for the greatest amount of variance in SZ (compared to other PMPSs derived at more inclusivep-value thresholds). However, none of the PMPSs were associated with BD, or a combined cohort of BD and SZ cases relative to HCs. Results demonstrating elevated PMPSs in SZ relative to BD did not survive correction for multiple testing. PMPSs were also not associated with positive or negative symptom severity. That this SZ-derived PMPSs was elevated among SZ, but not BD participants, suggests that epigenome-wide methylation patterns associated with schizophrenia may represent distinct pathophysiology that is yet to be elucidated. Whether this PMPS may be associated with neuroanatomical or other biological endophenotypes relevant to SZ and/or BD remains to be determined.

scholarly journals Paternal body mass index and offspring DNA methylation: findings from the PACE consortium

2020 ◽  
Author(s):  
Gemma C Sharp ◽  
Rossella Alfano ◽  
Akram Ghantous ◽  
Jose Urquiza ◽  
Sheryl L Rifas-Shiman ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Health Outcomes ◽  
Candidate Gene ◽  
Body Mass ◽  
Association Studies ◽  
Meta Analysis ◽  
450K Array ◽  
Total N ◽  
Candidate Gene Studies

AbstractBackgroundAccumulating evidence links paternal adiposity in the peri-conceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans.Methods and findingsIn the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-analysis of co-ordinated epigenome-wide association studies (EWAS) of paternal prenatal Body Mass Index (BMI) (with and without adjustment for maternal BMI) in relation to DNA methylation in offspring blood at birth (13 datasets; total n= 4,894) and in childhood (six datasets; total n = 1,982). We found little evidence of association at either time point: for all CpGs, the False Discovery Rate-adjusted P-values were >0.05. In sex-stratified analyses, we found just four CpGs where there was robust evidence of association in female offspring. To compare our findings to those of other studies, we conducted a systematic review, which identified seven studies, including five candidate gene studies showing associations between paternal BMI/obesity and offspring or sperm DNA methylation at imprinted regions. However, in our own study, we found very little evidence of enrichment for imprinted genes.ConclusionOur findings do not support the hypothesis that paternal BMI around the time of pregnancy is associated with offspring blood DNA methylation, even at imprinted regions.Author SummaryPrevious small, mostly candidate gene studies have shown associations between paternal pre-pregnancy BMI and offspring blood DNA methylation. However, in our large meta-analysis of co-ordinated EWAS results from a total of 19 datasets across two timepoints, we found little evidence to support these findings, even at imprinted regions. This does not rule out the possibility of a paternal epigenetic effect in different tissues, at regions not covered by the 450k array, via different mechanisms, or in populations with greater extremes of paternal BMI. More research is warranted to help understand the size and nature of contributions of paternal adiposity to offspring epigenetics and health outcomes.

scholarly journals Replication and expansion of epigenome-wide association literature in a black South African population

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
H. Toinét Cronjé ◽  
Hannah R. Elliott ◽  
Cornelie Nienaber-Rousseau ◽  
Marlien Pieters
Keyword(s):  
Dna Methylation ◽  
Alcohol Consumption ◽  
South African ◽  
Large Scale ◽  
Association Studies ◽  
African Population ◽  
450K Array ◽  
Related Factors ◽  
Successful Replication ◽  
Novel Associations

Abstract Background DNA methylation is associated with non-communicable diseases (NCDs) and related traits. Methylation data on continental African ancestries are currently scarce, even though there are known genetic and epigenetic differences between ancestral groups and a high burden of NCDs in Africans. Furthermore, the degree to which current literature can be extrapolated to the understudied African populations, who have limited resources to conduct independent large-scale analysis, is not yet known. To this end, this study examines the reproducibility of previously published epigenome-wide association studies of DNA methylation conducted in different ethinicities, on factors related to NCDs, by replicating findings in 120 South African Batswana men aged 45 to 88 years. In addition, novel associations between methylation and NCD-related factors are investigated using the Illumina EPIC BeadChip. Results Up to 86% of previously identified epigenome-wide associations with NCD-related traits (alcohol consumption, smoking, body mass index, waist circumference, C-reactive protein, blood lipids and age) overlapped with those observed here and a further 13% were directionally consistent. Only 1% of the replicated associations presented with effects opposite to findings in other ancestral groups. The majority of these inconcistencies were associated with population-specific genomic variance. In addition, we identified eight new 450K array CpG associations not previously reported in other ancestries, and 11 novel EPIC CpG associations with alcohol consumption. Conclusions The successful replication of existing EWAS findings in this African population demonstrates that blood-based 450K EWAS findings from commonly investigated ancestries can largely be extrapolated to ethnicities for which epigenetic data are not yet available. Possible population-specific differences in 14% of the tested associations do, however, motivate the need to include a diversity of ethnic groups in future epigenetic research. The novel associations found with the enhanced coverage of the Illumina EPIC array support its usefulness to expand epigenetic literature.

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