scholarly journals Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Irma Karabegović ◽  
Eliana Portilla-Fernandez ◽  
Yang Li ◽  
Jiantao Ma ◽  
Silvana C. E. Maas ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Association Studies ◽  
Meta Analysis ◽  
Disease Onset ◽  
Coffee Consumption ◽  
Tea Consumption ◽  
Hepatic Lipid Metabolism ◽  
Significance Threshold ◽  
Suggestive Association

AbstractCoffee and tea are extensively consumed beverages worldwide which have received considerable attention regarding health. Intake of these beverages is consistently linked to, among others, reduced risk of diabetes and liver diseases; however, the mechanisms of action remain elusive. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. Here we report the results from epigenome-wide association studies (EWAS) on coffee and tea consumption in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis of coffee consumption reveals 11 CpGs surpassing the epigenome-wide significance threshold (P-value <1.1×10−7), which annotated to the AHRR, F2RL3, FLJ43663, HDAC4, GFI1 and PHGDH genes. Among them, cg14476101 is significantly associated with expression of the PHGDH and risk of fatty liver disease. Knockdown of PHGDH expression in liver cells shows a correlation with expression levels of genes associated with circulating lipids, suggesting a role of PHGDH in hepatic-lipid metabolism. EWAS meta-analysis on tea consumption reveals no significant association, only two CpGs annotated to CACNA1A and PRDM16 genes show suggestive association (P-value <5.0×10−6). These findings indicate that coffee-associated changes in DNA methylation levels may explain the mechanism of action of coffee consumption in conferring risk of diseases.

scholarly journals Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption

2020 ◽  
Author(s):  
Irma Karabegović ◽  
Eliana Portilla-Fernandez ◽  
Yang Li ◽  
Jiantao Ma ◽  
Silvana C.E. Maas ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Observational Studies ◽  
Disease Risk ◽  
Association Studies ◽  
Meta Analysis ◽  
Disease Onset ◽  
Coffee Consumption ◽  
Tea Consumption ◽  
Hepatic Lipid Metabolism

AbstractCoffee and tea are extensively consumed beverages worldwide. Observational studies have shown contradictory findings for the association between consumption of these beverages and different health outcomes. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. We conducted epigenome-wide association studies (EWAS) on coffee and tea consumptions in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis revealed 11 CpG sites significantly associated with coffee consumption (P-value <1.1×10-7), nine of them annotated to the genes AHRR, F2RL3, FLJ43663, HDAC4, GFI1 and PHGDH, and two CpGs suggestively associated with tea consumption (P-value<5.0×10-6). Among these, cg14476101 was significantly associated with expression of its annotated gene PHGDH and risk of fatty liver disease. Knockdown of PHGDH expression in liver cells showed a correlation with expression levels of lipid-associated genes, suggesting a role of PHGDH in hepatic-lipid metabolism. Collectively, this study indicates that coffee consumption is associated with differential DNA methylation levels at multiple CpGs, and that coffee-associated epigenetic variations may explain the mechanism of action of coffee consumption in conferring disease risk.

scholarly journals A systematic review and meta-analysis of genetic association studies for the role of inflammation and the immune system in diabetic nephropathy

2017 ◽  
Vol 10 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Maria Tziastoudi ◽  
Ioannis Stefanidis ◽  
Georgios M. Hadjigeorgiou ◽  
Konstantinos Stravodimos ◽  
Elias Zintzaras
Keyword(s):  
Systematic Review ◽  
Diabetic Nephropathy ◽  
Immune System ◽  
Genetic Association ◽  
Association Studies ◽  
Meta Analysis ◽  
Genetic Association Studies

scholarly journals Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

2019 ◽  
Author(s):  
Tianye Jia ◽  
Congying Chu ◽  
Yun Liu ◽  
Jenny van Dongen ◽  
Evangelos Papastergios ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Nucleus Accumbens ◽  
Large Scale ◽  
Biomarker Discovery ◽  
Association Studies ◽  
Meta Analysis ◽  
Hippocampal Volume ◽  
Small Sample ◽  
Small Sample Sizes ◽  
Meta Analyses

AbstractDNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.

scholarly journals Association between DNA methylation and ADHD symptoms from birth to school age: a prospective meta-analysis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexander Neumann ◽  
Esther Walton ◽  
Silvia Alemany ◽  
Charlotte Cecil ◽  
Juan Ramon González ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Neurotransmitter Release ◽  
Association Studies ◽  
Meta Analysis ◽  
School Age ◽  
Adhd Symptoms ◽  
Future Studies ◽  
Hyperactivity Disorder ◽  
Causal Pathways ◽  
Nominal Significance

AbstractAttention-deficit and hyperactivity disorder (ADHD) is a common childhood disorder with a substantial genetic component. However, the extent to which epigenetic mechanisms play a role in the etiology of the disorder is unknown. We performed epigenome-wide association studies (EWAS) within the Pregnancy And Childhood Epigenetics (PACE) Consortium to identify DNA methylation sites associated with ADHD symptoms at two methylation assessment periods: birth and school age. We examined associations of both DNA methylation in cord blood with repeatedly assessed ADHD symptoms (age 4–15 years) in 2477 children from 5 cohorts and of DNA methylation at school age with concurrent ADHD symptoms (age 7–11 years) in 2374 children from 9 cohorts, with 3 cohorts participating at both timepoints. CpGs identified with nominal significance (p < 0.05) in either of the EWAS were correlated between timepoints (ρ = 0.30), suggesting overlap in associations; however, top signals were very different. At birth, we identified nine CpGs that predicted later ADHD symptoms (p < 1 × 10–7), including ERC2 and CREB5. Peripheral blood DNA methylation at one of these CpGs (cg01271805 in the promoter region of ERC2, which regulates neurotransmitter release) was previously associated with brain methylation. Another (cg25520701) lies within the gene body of CREB5, which previously was associated with neurite outgrowth and an ADHD diagnosis. In contrast, at school age, no CpGs were associated with ADHD with p < 1 × 10−7. In conclusion, we found evidence in this study that DNA methylation at birth is associated with ADHD. Future studies are needed to confirm the utility of methylation variation as biomarker and its involvement in causal pathways.

scholarly journals The diagnostic role of DNA methylation in sporadic endometrial cancer: a systematic review and meta-analysis

Oncotarget ◽  
2017 ◽  
Vol 9 (9) ◽  
pp. 8642-8652 ◽  
Author(s):  
Yu Fan ◽  
Yu Wang ◽  
Shaozhi Fu ◽  
Linglin Yang ◽  
Sheng Lin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Dna Methylation ◽  
Endometrial Cancer ◽  
Meta Analysis ◽  
Diagnostic Role

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 Meta-analysis of epigenome-wide association studies in Alzheimer’s disease highlights novel differentially methylated loci across cortex

2020 ◽  
Author(s):  
Rebecca G. Smith ◽  
Ehsan Pishva ◽  
Gemma Shireby ◽  
Adam R. Smith ◽  
Janou A.Y. Roubroeks ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Studies ◽  
Meta Analysis ◽  
Brain Regions ◽  
Braak Stage ◽  
Combine Data ◽  
Online Data ◽  
Data Resource ◽  
Significance Threshold

ABSTRACTEpigenome-wide association studies of Alzheimer’s disease have highlighted neuropathology-associated DNA methylation differences, although existing studies have been limited in sample size and utilized different brain regions. Here, we combine data from six DNA methylomic studies of Alzheimer’s disease (N=1,453 unique individuals) to identify differential methylation associated with Braak stage in different brain regions and across cortex. We identified 236 CpGs in the prefrontal cortex, 95 CpGs in the temporal gyrus and ten CpGs in the entorhinal cortex at Bonferroni significance, with none in the cerebellum. Our cross-cortex meta-analysis (N=1,408 donors) identified 220 CpGs associated with neuropathology, annotated to 121 genes, of which 84 genes had not been previously reported at this significance threshold. We have replicated our findings using two further DNA methylomic datasets consisting of a > 600 further unique donors. The meta-analysis summary statistics are available in our online data resource (www.epigenomicslab.com/ad-meta-analysis/).

scholarly journals Evidence for Association of the E23K Variant ofKCNJ11Gene with Type 2 Diabetes in Tunisian Population: Population-Based Study and Meta-Analysis

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Khaled Lasram ◽  
Nizar Ben Halim ◽  
Sana Hsouna ◽  
Rym Kefi ◽  
Imen Arfa ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Studies ◽  
Meta Analysis ◽  
Population Based ◽  
Case Control ◽  
Tunisian Population ◽  
Allelic Association ◽  
Meta Analyses

Aims. Genetic association studies have reported the E23K variant ofKCNJ11gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations.Methods. We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been evaluated by 2 meta-analyses including all population-based studies among Tunisians and Arabs (2 and 5 populations, resp.).Results. A significant association between the E23K variant and Type 2 diabetes was found (OR = 1.6, 95% CI = 1.14–2.27, andP=0.007). Furthermore, our meta-analysis has confirmed the significant role of the E23K variant in susceptibility of Type 2 diabetes in Tunisian and Arab populations (OR = 1.29, 95% CI = 1.15–1.46, andP<10-3and OR = 1.33, 95% CI = 1.13–1.56, andP=0.001, resp.).Conclusion. Both case-control and meta-analyses results revealed the significant association between the E23K variant ofKCNJ11and Type 2 diabetes among Tunisians and Arabs.

scholarly journals A meta-analysis of epigenome-wide association studies in Alzheimer’s disease highlights novel differentially methylated loci across cortex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rebecca G. Smith ◽  
Ehsan Pishva ◽  
Gemma Shireby ◽  
Adam R. Smith ◽  
Janou A. Y. Roubroeks ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Studies ◽  
Meta Analysis ◽  
Brain Regions ◽  
Braak Stage ◽  
Combine Data ◽  
Online Data ◽  
Data Resource ◽  
Significance Threshold

AbstractEpigenome-wide association studies of Alzheimer’s disease have highlighted neuropathology-associated DNA methylation differences, although existing studies have been limited in sample size and utilized different brain regions. Here, we combine data from six DNA methylomic studies of Alzheimer’s disease (N = 1453 unique individuals) to identify differential methylation associated with Braak stage in different brain regions and across cortex. We identify 236 CpGs in the prefrontal cortex, 95 CpGs in the temporal gyrus and ten CpGs in the entorhinal cortex at Bonferroni significance, with none in the cerebellum. Our cross-cortex meta-analysis (N = 1408 donors) identifies 220 CpGs associated with neuropathology, annotated to 121 genes, of which 84 genes have not been previously reported at this significance threshold. We have replicated our findings using two further DNA methylomic datasets consisting of a further >600 unique donors. The meta-analysis summary statistics are available in our online data resource (www.epigenomicslab.com/ad-meta-analysis/).

scholarly journals DNA methylation of blood cells is associated with prevalent type 2 diabetes in a meta-analysis of four European cohorts

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Diana L. Juvinao-Quintero ◽  
Riccardo E. Marioni ◽  
Carolina Ochoa-Rosales ◽  
Tom C. Russ ◽  
Ian J. Deary ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Association Studies ◽  
Meta Analysis ◽  
Cell Types ◽  
Common Risk Factors ◽  
Variation Explained

Abstract Background Type 2 diabetes (T2D) is a heterogeneous disease with well-known genetic and environmental risk factors contributing to its prevalence. Epigenetic mechanisms related to changes in DNA methylation (DNAm), may also contribute to T2D risk, but larger studies are required to discover novel markers, and to confirm existing ones. Results We performed a large meta-analysis of individual epigenome-wide association studies (EWAS) of prevalent T2D conducted in four European studies using peripheral blood DNAm. Analysis of differentially methylated regions (DMR) was also undertaken, based on the meta-analysis results. We found three novel CpGs associated with prevalent T2D in Europeans at cg00144180 (HDAC4), cg16765088 (near SYNM) and cg24704287 (near MIR23A) and confirmed three CpGs previously identified (mapping to TXNIP, ABCG1 and CPT1A). We also identified 77 T2D associated DMRs, most of them hypomethylated in T2D cases versus controls. In adjusted regressions among diabetic-free participants in ALSPAC, we found that all six CpGs identified in the meta-EWAS were associated with white cell-types. We estimated that these six CpGs captured 11% of the variation in T2D, which was similar to the variation explained by the model including only the common risk factors of BMI, sex, age and smoking (R2 = 10.6%). Conclusions This study identifies novel loci associated with T2D in Europeans. We also demonstrate associations of the same loci with other traits. Future studies should investigate if our findings are generalizable in non-European populations, and potential roles of these epigenetic markers in T2D etiology or in determining long term consequences of T2D.

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