Genome-wide associations between alcohol consumption and blood DNA methylation: evidence from twin study

Epigenomics ◽  
2021 ◽  
Author(s):  
Meng Lu ◽  
Qin Xueying ◽  
Peng Hexiang ◽  
Gao Wenjing ◽  
Sara Hägg ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alcohol Consumption ◽  
Twin Study ◽  
Alcohol Intake ◽  
Entire Sample ◽  
Cpg Sites ◽  
Infinium Humanmethylation450 Beadchip ◽  
Twin Registry ◽  
Genome Wide ◽  
Mz Twins

Aim: Alcohol intake alters DNA methylation profiles and methylation might mediate the association between alcohol and disease, but limited number of positive CpG sites repeatedly replicated. Materials & methods: In total, 57 monozygotic (MZ) twin pairs discordant for alcohol drinking from the Chinese National Twin Registry and 158 MZ and dizygotic twin pairs in the Swedish Adoption/Twin Study of Aging were evaluated. DNA methylation was detected using the Infinium HumanMethylation450 BeadChip. Results: Among candidate CpG sites, cg07326074 was significantly correlated with drinking after adjusting for covariates in MZ twins in both datasets but not in the entire sample or dizygotic twins. Conclusion: The hypermethylation of cg07326074, located in the tumor-promoting gene C16orf59, was associated with alcohol consumption.

scholarly journals Socioeconomic status and DNA methylation from birth through mid-childhood: a prospective study in Project Viva

Epigenomics ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1413-1427 ◽  
Author(s):  
Zachary M Laubach ◽  
Wei Perng ◽  
Andres Cardenas ◽  
Sheryl L Rifas-Shiman ◽  
Emily Oken ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Socioeconomic Status ◽  
Cord Blood ◽  
Cpg Sites ◽  
Infinium Humanmethylation450 Beadchip ◽  
Genome Wide ◽  
Peripheral Leukocytes ◽  
A Prospective Study ◽  
The Relationship ◽  
Neighborhood Level

Aim: We investigated associations of prenatal socioeconomic status (SES) with DNA methylation at birth, and to explore persistence of associations into early (∼3 years) and mid-childhood (∼7 years) among 609 mother–child pairs in a Boston-area prebirth cohort. Materials & methods: First, we created a prenatal SES index comprising individual- and neighborhood-level metrics and examined associations of low (lowest 10%) versus high (upper 90%) SES with genome-wide DNA methylation in cord blood via the Infinium HumanMethylation450 BeadChip. Next, we evaluated persistence of associations detected in cord blood with DNA methylation of the same CpG sites measured in peripheral leukocytes in early- and mid-childhood. Results & conclusion: Low prenatal SES was associated with methylation at CpG sites near ACSF3, TNRC6C-AS1, MTMR4 and LRRN4. The relationship with LRRN4 persisted into early childhood.

scholarly journals DNA methylation mediates the association between breastfeeding and early-life growth trajectories

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Laurent Briollais ◽  
Denis Rustand ◽  
Catherine Allard ◽  
Yanyan Wu ◽  
Jingxiong Xu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Signaling Pathway ◽  
Exclusive Breastfeeding ◽  
Child Growth ◽  
Postnatal Period ◽  
Overweight And Obesity ◽  
Breastfeeding Duration ◽  
Ampk Signaling ◽  
Cpg Sites ◽  
Genome Wide

Abstract Background The role of breastfeeding in modulating epigenetic factors has been suggested as a possible mechanism conferring its benefits on child development but it lacks evidence. Using extensive DNA methylation data from the ALSPAC child cohort, we characterized the genome-wide landscape of DNA methylation variations associated with the duration of exclusive breastfeeding and assessed whether these variations mediate the association between exclusive breastfeeding and BMI over different epochs of child growth. Results Exclusive breastfeeding elicits more substantial DNA methylation variations during infancy than at other periods of child growth. At the genome-wide level, 13 CpG sites in girls (miR-21, SNAPC3, ATP6V0A1, DHX15/PPARGC1A, LINC00398/ALOX5AP, FAM238C, NATP/NAT2, CUX1, TRAPPC9, OSBPL1A, ZNF185, FAM84A, PDPK1) and 2 CpG sites in boys (IL16 and NREP), mediate the association between exclusive breastfeeding and longitudinal BMI. We found enrichment of CpG sites located within miRNAs and key pathways (AMPK signaling pathway, insulin signaling pathway, endocytosis). Overall DNA methylation variation corresponding to 3 to 5 months of exclusive breastfeeding was associated with slower BMI growth the first 6 years of life compared to no breastfeeding and in a dose–response manner with exclusive breastfeeding duration. Conclusions Our study confirmed the early postnatal period as a critical developmental period associated with substantial DNA methylation variations, which in turn could mitigate the development of overweight and obesity from infancy to early childhood. Since an accelerated growth during these developmental periods has been linked to the development of sustained obesity later in life, exclusive breastfeeding could have a major role in preventing the risks of overweight/obesity and children and adults through DNA methylation mechanisms occurring early in life.

Abstract P098: An Epigenome-wide Study of Obesity in African American Youth and Young Adults: Novel Findings, Replication in Neutrophils and Relationship With Gene Expression

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Xiaoling Wang ◽  
Yue Pan ◽  
Haidong Zhu ◽  
Guang Hao ◽  
Xin Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Older Adults ◽  
Dna Methylation ◽  
Young Adults ◽  
Methylation Data ◽  
Middle Aged ◽  
Cpg Sites ◽  
Genome Wide ◽  
Obesity Status ◽  
Youth And Young Adults

Background: Several large-scale epigenome wide association studies on obesity-related DNA methylation changes have been published and in total identified 46 CpG sites. These studies were conducted in middle-aged and older adults of Caucasians and African Americans (AAs) using leukocytes. To what extend these signals are independent of cell compositions as well as to what extend they may influence gene expression have not been systematically investigated. Furthermore, the high prevalence of obesity comorbidities in middle-aged or older population may hide or bias obesity itself related DNA methylation changes. Methods: In this study of healthy AA youth and young adults, genome wide DNA methylation data from leukocytes were obtained from three independent studies: EpiGO study (96 obese cases vs. 92 lean controls, aged 14-21, 50% females, test of interest is obesity status), LACHY study (284 participants from general population, aged 14-18, 50% females, test of interest is BMI), and Georgia Stress and Heart study (298 participants from general population, aged 18-38, 52% females, test of interest is BMI) using the Infinium HumanMethylation450 BeadChip. Genome wide DNA methylation data from purified neutrophils as well as genome wide gene expression data from leukocytes using Illumina HT12 V4 array were also obtained for the EpiGO samples. Results: The meta-analysis on the 3 cohorts identified 76 obesity related CpG sites in leukocytes with p<1х10 -7 . Out of the 46 previously identified CpG sites, 36 can be replicated in this AA youth and young adult sample with same direction and p<0.05. Out of the 107 CpG sites including the 36 replicated ones and the 71 newly identified ones, 71 CpG sites (66%) had their relationship with obesity replicated in purified neutrophils (p<0.05). The analysis on the cis regulation of the 107 CpG sites on gene expression showed that 59 CpG sites had at least one gene within 250kb having expression difference between obese cases and lean controls. Furthermore, out of the 59 CpG sites, 6 showed significantly negative correlations and 1 showed significantly positive correlation with the differentially expressed genes. These CpG sites located in SOCS3, CISH, ABCG1, PIM3 and PTGDS genes. Conclusion: In this study of AA youth and young adults, we identified novel CpG sites associated with obesity and replicated majority of the CpG sites previously identified in middle-aged and older adults. For the first time, we showed that majority of the obesity related CpG sites identified from leukocytes are not driven by cell compositions and provided the direct link between DNA methylation-gene expression-obesity status for 7 CpG sites in 5 genes.

scholarly journals Changes in DNA Methylation and Gene Expression of Insulin and Obesity-Related Gene PIK3R1 after Roux-en-Y Gastric Bypass

2020 ◽  
Vol 21 (12) ◽  
pp. 4476
Author(s):  
Marcela A S Pinhel ◽  
Natália Y Noronha ◽  
Carolina F Nicoletti ◽  
Vanessa AB Pereira ◽  
Bruno AP de Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Weight Loss ◽  
Gastric Bypass ◽  
Related Gene ◽  
Cpg Sites ◽  
Genome Wide ◽  
Genetically Determined ◽  
Methylation Patterns ◽  
Weight Loss Interventions

Weight regulation and the magnitude of weight loss after a Roux-en-Y gastric bypass (RYGB) can be genetically determined. DNA methylation patterns and the expression of some genes can be altered after weight loss interventions, including RYGB. The present study aimed to evaluate how the gene expression and DNA methylation of PIK3R1, an obesity and insulin-related gene, change after RYGB. Blood samples were obtained from 13 women (35.9 ± 9.2 years) with severe obesity before and six months after surgical procedure. Whole blood transcriptome and epigenomic patterns were assessed by microarray-based, genome-wide technologies. A total of 1966 differentially expressed genes were identified in the pre- and postoperative periods of RYGB. From these, we observed that genes involved in obesity and insulin pathways were upregulated after surgery. Then, the PIK3R1 gene was selected for further RT-qPCR analysis and cytosine-guanine nucleotide (CpG) sites methylation evaluation. We observed that the PI3KR1 gene was upregulated, and six DNA methylation CpG sites were differently methylated after bariatric surgery. In conclusion, we found that RYGB upregulates genes involved in obesity and insulin pathways.

scholarly journals Epigenome-Wide DNA Methylation Analysis of Monozygotic Twins Discordant for Diurnal Preference

2015 ◽  
Vol 18 (6) ◽  
pp. 662-669 ◽  
Author(s):  
Chloe C. Y. Wong ◽  
Michael J. Parsons ◽  
Kathryn J. Lester ◽  
Joe Burrage ◽  
Thalia C. Eley ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Circadian Clock ◽  
Monozygotic Twins ◽  
Enrichment Analysis ◽  
Genome Wide ◽  
Analysis Strategy ◽  
Diurnal Preference ◽  
Significant Enrichment ◽  
Longitudinal Twin Study ◽  
Mz Twins

Diurnal preference is an individual's preference for daily activities and sleep timing and is strongly correlated with the underlying circadian clock and the sleep-wake cycle validating its use as an indirect circadian measure in humans. Recent research has implicated DNA methylation as a mechanism involved in the regulation of the circadian clock system in humans and other mammals. In order to evaluate the extent of epigenetic differences associated with diurnal preference, we examined genome-wide patterns of DNA methylation in DNA from monozygotic (MZ) twin-pairs discordant for diurnal preference. MZ twins were selected from a longitudinal twin study designed to investigate the interplay of genetic and environmental factors in the development of emotional and behavioral difficulties. Fifteen pairs of MZ twins were identified in which one member scored considerably higher on the Horne–Ostberg Morningness–Eveningness Questionnaire (MEQ) than the other. Genome-wide DNA methylation patterns were assessed in twins’ buccal cell DNA using the Illumina Infinium HumanMethylation450 BeadChips. Quality control and data pre-processing was undertaken using the wateRmelon package. Differentially methylated probes (DMPs) were identified using an analysis strategy taking into account both the significance and the magnitude of DNA methylation differences. Our data indicate that DNA methylation differences are detectable in MZ twins discordant for diurnal preference. Moreover, downstream gene ontology (GO) enrichment analysis on the top-ranked diurnal preference associated DMPs revealed significant enrichment of pathways that have been previously associated with circadian rhythm regulation, including cell adhesion processes and calcium ion binding.

scholarly journals Genome-wide DNA methylation profile of early-onset endometrial cancer: its correlation with genetic aberrations and comparison with late-onset endometrial cancer

2019 ◽  
Vol 40 (5) ◽  
pp. 611-623 ◽  
Author(s):  
Takeshi Makabe ◽  
Eri Arai ◽  
Takuro Hirano ◽  
Nanako Ito ◽  
Yukihiro Fukamachi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Endometrial Cancer ◽  
Early Onset ◽  
Late Onset ◽  
Methylation Profile ◽  
Cancer Tissue ◽  
Cpg Sites ◽  
Genome Wide ◽  
Dna Methylation Profile ◽  
Endometrioid Endometrial Cancer

Abstract The present study was performed to clarify the significance of DNA methylation alterations during endometrial carcinogenesis. Genome-wide DNA methylation analysis and targeted sequencing of tumor-related genes were performed using the Infinium MethylationEPIC BeadChip and the Ion AmpliSeq Cancer Hotspot Panel v2, respectively, for 31 samples of normal control endometrial tissue from patients without endometrial cancer and 81 samples of endometrial cancer tissue. Principal component analysis revealed that tumor samples had a DNA methylation profile distinct from that of control samples. Gene Ontology enrichment analysis revealed significant differences of DNA methylation at 1034 CpG sites between early-onset endometrioid endometrial cancer (EE) tissue (patients aged ≤40 years) and late-onset endometrioid endometrial cancer (LE) tissue, which were accumulated among ‘transcriptional factors’. Mutations of the CTNNB1 gene or DNA methylation alterations of genes participating in Wnt signaling were frequent in EEs, whereas genetic and epigenetic alterations of fibroblast growth factor signaling genes were observed in LEs. Unsupervised hierarchical clustering grouped EE samples in Cluster EA (n = 22) and samples in Cluster EB (n = 12). Clinicopathologically less aggressive tumors tended to be accumulated in Cluster EB, and DNA methylation levels of 18 genes including HOXA9, HOXD10 and SOX11 were associated with differences in such aggressiveness between the two clusters. We identified 11 marker CpG sites that discriminated EB samples from EA samples with 100% sensitivity and specificity. These data indicate that genetically and epigenetically different pathways may participate in the development of EEs and LEs, and that DNA methylation profiling may help predict tumors that are less aggressive and amenable to fertility preservation treatment.

scholarly journals Testing cell-type-specific mediation effects in genome-wide epigenetic studies

2020 ◽  
Author(s):  
Xiangyu Luo ◽  
Joel Schwartz ◽  
Andrea Baccarelli ◽  
Zhonghua Liu
Keyword(s):  
Dna Methylation ◽  
Mediation Analysis ◽  
Methylation Data ◽  
Cell Type ◽  
Multiple Testing Procedure ◽  
Mediation Effects ◽  
Cpg Sites ◽  
Genome Wide ◽  
A Cell ◽  
Cell Type Specific

Abstract Epigenome-wide mediation analysis aims to identify DNA methylation CpG sites that mediate the causal effects of genetic/environmental exposures on health outcomes. However, DNA methylations in the peripheral blood tissues are usually measured at the bulk level based on a heterogeneous population of white blood cells. Using the bulk level DNA methylation data in mediation analysis might cause confounding bias and reduce study power. Therefore, it is crucial to get fine-grained results by detecting mediation CpG sites in a cell-type-specific way. However, there is a lack of methods and software to achieve this goal. We propose a novel method (Mediation In a Cell-type-Specific fashion, MICS) to identify cell-type-specific mediation effects in genome-wide epigenetic studies using only the bulk-level DNA methylation data. MICS follows the standard mediation analysis paradigm and consists of three key steps. In step1, we assess the exposure-mediator association for each cell type; in step 2, we assess the mediator-outcome association for each cell type; in step 3, we combine the cell-type-specific exposure-mediator and mediator-outcome associations using a multiple testing procedure named MultiMed [Sampson JN, Boca SM, Moore SC, et al. FWER and FDR control when testing multiple mediators. Bioinformatics 2018;34:2418–24] to identify significant CpGs with cell-type-specific mediation effects. We conduct simulation studies to demonstrate that our method has correct FDR control. We also apply the MICS procedure to the Normative Aging Study and identify nine DNA methylation CpG sites in the lymphocytes that might mediate the effect of cigarette smoking on the lung function.

Genome-Wide DNA Methylation Analysis Shows Enrichment of Differential Methylation in “Open Seas” and Enhancers and Reveals Hypomethylation in DNMT3A Mutated Cytogenetically Normal AML (CN-AML)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 653-653 ◽  
Author(s):  
Ying Qu ◽  
Andreas Lennartsson ◽  
Verena I. Gaidzik ◽  
Stefan Deneberg ◽  
Sofia Bengtzén ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cpg Island ◽  
Cpg Islands ◽  
Differential Methylation ◽  
Methylation Analysis ◽  
Cpg Sites ◽  
Genome Wide ◽  
Genomic Regions ◽  
Methylation Patterns

Abstract Abstract 653 DNA methylation is involved in multiple biologic processes including normal cell differentiation and tumorigenesis. In AML, methylation patterns have been shown to differ significantly from normal hematopoietic cells. Most studies of DNA methylation in AML have previously focused on CpG islands within the promoter of genes, representing only a very small proportion of the DNA methylome. In this study, we performed genome-wide methylation analysis of 62 AML patients with CN-AML and CD34 positive cells from healthy controls by Illumina HumanMethylation450K Array covering 450.000 CpG sites in CpG islands as well as genomic regions far from CpG islands. Differentially methylated CpG sites (DMS) between CN-AML and normal hematopoietic cells were calculated and the most significant enrichment of DMS was found in regions more than 4kb from CpG Islands, in the so called open sea where hypomethylation was the dominant form of aberrant methylation. In contrast, CpG islands were not enriched for DMS and DMS in CpG islands were dominated by hypermethylation. DMS successively further away from CpG islands in CpG island shores (up to 2kb from CpG Island) and shelves (from 2kb to 4kb from Island) showed increasing degree of hypomethylation in AML cells. Among regions defined by their relation to gene structures, CpG dinucleotide located in theoretic enhancers were found to be the most enriched for DMS (Chi χ2<0.0001) with the majority of DMS showing decreased methylation compared to CD34 normal controls. To address the relation to gene expression, GEP (gene expression profiling) by microarray was carried out on 32 of the CN-AML patients. Totally, 339723 CpG sites covering 18879 genes were addressed on both platforms. CpG methylation in CpG islands showed the most pronounced anti-correlation (spearman ρ =-0.4145) with gene expression level, followed by CpG island shores (mean spearman rho for both sides' shore ρ=-0.2350). As transcription factors (TFs) have shown to be crucial for AML development, we especially studied differential methylation of an unbiased selection of 1638 TFs. The most enriched differential methylation between CN-AML and normal CD34 positive cells were found in TFs known to be involved in hematopoiesis and with Wilms tumor protein-1 (WT1), activator protein 1 (AP-1) and runt-related transcription factor 1 (RUNX1) being the most differentially methylated TFs. The differential methylation in WT 1 and RUNX1 was located in intragenic regions which were confirmed by pyro-sequencing. AML cases were characterized with respect to mutations in FLT3, NPM1, IDH1, IDH2 and DNMT3A. Correlation analysis between genome wide methylation patterns and mutational status showed statistically significant hypomethylation of CpG Island (p<0.0001) and to a lesser extent CpG island shores (p<0.001) and the presence of DNMT3A mutations. This links DNMT3A mutations for the first time to a hypomethylated phenotype. Further analyses correlating methylation patterns to other clinical data such as clinical outcome are ongoing. In conclusion, our study revealed that non-CpG island regions and in particular enhancers are the most aberrantly methylated genomic regions in AML and that WT 1 and RUNX1 are the most differentially methylated TFs. Furthermore, our data suggests a hypomethylated phenotype in DNMT3A mutated AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Genome-wide DNA methylation can identify preterm birth-related genes in maternal blood

2020 ◽  
Author(s):  
Young-Ah You ◽  
Eun Jin Kwon ◽  
Han-Sung Hwang ◽  
Suk-Joo Choi ◽  
Sae Kyung Choi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Preterm Birth ◽  
Maternal Blood ◽  
Differential Methylation ◽  
Multiple Tests ◽  
Cpg Sites ◽  
Genome Wide ◽  
Increased Risk ◽  
Health And Disease ◽  
Whole Blood Cells

Abstract Background Preterm birth is associated with an increased risk of neonatal complications and death, as well as poor health and disease later in life. Epigenetics could contribute to the mechanism underlying preterm birth. Results Genome-wide DNA methylation in whole blood cells from ten women was assessed using Illumina Infinium HumanMethylation450 BeadChips array. We identified 6,755 differentially methylated CpG sites between term and preterm birth. Although no differential methylation of these CpGs were found in correcting for multiple tests, seven VTRNA2-1 CpGs in promotor region of island were detected in top different methylation. We performed pyrosequencing validation with blood samples from the pregnant women. The methylation levels of VTRNA2-1 were either low (hypomethylated, 0–12.2%) or high (hypermethylated, 32.6–50.8%). Hypermethylation of VTRNA2-1 was associated with an increased risk of preterm birth after adjusting for maternal age, delivered season, parity and count of white blood cell. The mRNA expression of VTRNA2-1 was 0.51-fold lower in PTB delivered women compared with women with term deliveries. Conclusion This study suggests that change of VTRNA2-1 methylation is related to PTB in maternal blood. Further elucidate to underlay mechanisms of preterm birth and affect to future systems biology studies to predict preterm birth.

scholarly journals Alcohol consumption and methylation-based measures of biological age

2021 ◽  
Author(s):  
Jacob K Kresovich ◽  
Alexandra M Martinez Lopez ◽  
Emma L Garval ◽  
Zongli Xu ◽  
Alexandra J White ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alcohol Consumption ◽  
Biological Age ◽  
Average Lifetime ◽  
Epigenetic Clock ◽  
Genome Wide ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration ◽  
The Mean ◽  
Average Consumption

Abstract Epigenetic age acceleration is considered a measure of biological aging based on genome-wide patterns of DNA methylation. Although age acceleration has been associated with incidence of diseases and death, less is known about how it is related to lifestyle behaviors. Among 2,316 women, we evaluate associations between self-reported alcohol consumption and various metrics of epigenetic age acceleration. Recent average alcohol consumption was defined as the mean number of drinks consumed per week within the past year; lifetime average consumption was estimated as the mean number of drinks per year drinking. Whole blood genome-wide DNA methylation was measured with HumanMethylation450 BeadChips and used to assess four epigenetic clocks (Hannum, Horvath, PhenoAge, GrimAge) and their corresponding metrics of epigenetic age acceleration (Hannum AgeAccel, Horvath AgeAccel, PhenoAgeAccel, GrimAgeAccel). Although alcohol consumption showed little association with most age acceleration metrics, both lifetime and recent average consumption measures were positively associated with GrimAgeAccel (lifetime, per additional 135 drinks/year: β=0.30 years, 95% CI: 0.11, 0.48, p=0.002; recent, per additional 5 drinks/week: β=0.19 years, 95% CI: 0.01, 0.37, p=0.04). In a mutually adjusted model, only average lifetime alcohol consumption remained associated with GrimAgeAccel (lifetime, per additional 135 drinks/year: β=0.27 years, 95% CI: 0.04, 0.50, p=0.02; recent, per 5 additional drinks/week: β=0.05 years, 95% CI: -0.16, 0.26, p=0.64). Although alcohol use does not appear to be strongly associated with biological age measured by most epigenetic clocks, lifetime average consumption is associated with higher biological age assessed by the GrimAge epigenetic clock.

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