scholarly journals Alcohol consumption is associated with widespread changes in blood DNA methylation: analysis of cross-sectional and longitudinal data

2018 ◽  
Author(s):  
Pierre-Antoine Dugué ◽  
Rory Wilson ◽  
Benjamin Lehne ◽  
Harindra Jayasekara ◽  
Xiaochuan Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alcohol Consumption ◽  
Large Scale ◽  
Alcohol Intake ◽  
Methylation Status ◽  
Repeated Measurements ◽  
Cross Sectional ◽  
Blood Samples ◽  
Melbourne Collaborative Cohort Study ◽  
Risk Of Disease

ABSTRACTBackground:DNA methylation may be one of the mechanisms by which alcohol consumption is associated with the risk of disease. We conducted a large-scale, cross-sectional, genome-wide DNA methylation association study of alcohol consumption and a longitudinal analysis of repeated measurements taken several years apart.Methods:Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined using baseline peripheral blood samples from 5,606 adult Melbourne Collaborative Cohort Study (MCCS) participants. For a subset of 1,088 of them, these measures were repeated using blood samples collected at follow-up, a median of 11 years later. Associations between alcohol intake and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. Independent data from the LOLIPOP (N=4,042) and KORA (N=1,662) cohorts were used to replicate associations discovered in the MCCS.Results:Cross-sectional analyses identified 1,414 CpGs associated with alcohol intake at P<10-7, 1,243 of which had not been reported previously. Of these 1,243 novel associations, 1,078 were replicated (P<0.05) using LOLIPOP and KORA data. Using the MCCS data, we also replicated (P<0.05) 403 of 518 associations that had been reported previously. Interaction analyses suggested that associations were stronger for women, non-smokers, and participants genetically predisposed to consume less alcohol. Of the 1,414 CpGs, 530 were differentially methylated (P<0.05) in former compared with current drinkers. Longitudinal associations between the change in alcohol intake and the change in methylation were observed for 513 of the 1,414 cross-sectional associations.Conclusion:Our study indicates that, for middle-aged and older adults, alcohol intake is associated with widespread changes in DNA methylation across the genome. Longitudinal analyses showed that the methylation status of alcohol-associated CpGs may change with changes in alcohol consumption.

Progressive alteration of DNA methylation of Alu, MGMT, MINT2, and TFPI2 genes in colonic mucosa during colorectal cancer development

2021 ◽  
pp. 1-6
Author(s):  
Ben Kang ◽  
Hyun Seok Lee ◽  
Seong Woo Jeon ◽  
Soo Yeun Park ◽  
Gyu Seog Choi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Healthy Subjects ◽  
Large Scale ◽  
Methylation Status ◽  
Clinical Information ◽  
Field Cancerization ◽  
Aberrant Methylation ◽  
Clinical Value ◽  
Mortality And Morbidity

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. It is characterized by different pathways of carcinogenesis and is a heterogeneous disease with diverse molecular landscapes that reflect histopathological and clinical information. Changes in the DNA methylation status of colon epithelial cells have been identified as critical components in CRC development and appear to be emerging biomarkers for the early detection and prognosis of CRC. OBJECTIVE: To explore the underlying disease mechanisms and identify more effective biomarkers of CRC. METHODS: We compared the levels and frequencies of DNA methylation in 11 genes (Alu, APC, DAPK, MGMT, MLH1, MINT1, MINT2, MINT3, p16, RGS6, and TFPI2) in colorectal cancer and its precursor adenomatous polyp with normal tissue of healthy subjects using pyrosequencing and then evaluated the clinical value of these genes. RESULTS: Aberrant methylation of Alu, MGMT, MINT2, and TFPI2 genes was progressively accumulated during the normal-adenoma-carcinoma progression. Additionally, CGI methylation occurred either as an adenoma-associated event for APC, MLH1, MINT1, MINT31, p16, and RGS6 or a tumor-associated event for DAPK. Moreover, relatively high levels and frequencies of DAPK, MGMT, and TFPI2 methylation were detected in the peritumoral nonmalignant mucosa of cancer patients in a field-cancerization manner, as compared to normal mucosa from healthy subjects. CONCLUSION: This study identified several biomarkers associated with the initiation and progression of CRC. As novel findings, they may have important clinical implications for CRC diagnostic and prognostic applications. Further large-scale studies are needed to confirm these findings.

scholarly journals Bisphenol a Exposure, DNA Methylation, and Asthma in Children

2020 ◽  
Vol 17 (1) ◽  
pp. 298 ◽  
Author(s):  
Chia-Feng Yang ◽  
Wilfried J. J. Karmaus ◽  
Chen-Chang Yang ◽  
Mei-Lien Chen ◽  
I-Jen Wang
Keyword(s):  
Dna Methylation ◽  
Bisphenol A ◽  
Candidate Genes ◽  
Promoter Methylation ◽  
Childhood Asthma ◽  
Methylation Status ◽  
Differential Methylation ◽  
Study Cohort ◽  
Blood Samples ◽  
Asthma In Children

Epidemiological studies have reported the relationship between bisphenol A (BPA) exposure and increased prevalence of asthma, but the mechanisms remain unclear. Here, we investigated whether BPA exposure and DNA methylation related to asthma in children. We collected urinary and blood samples from 228 children (Childhood Environment and Allergic Diseases Study cohort) aged 3 years. Thirty-three candidate genes potentially interacting with BPA exposure were selected from a toxicogenomics database. DNA methylation was measured in 22 blood samples with top-high and bottom-low exposures of BPA. Candidate genes with differential methylation levels were validated by qPCR and promoter associated CpG islands have been investigated. Correlations between the methylation percentage and BPA exposure and asthma were analyzed. According to our findings, MAPK1 showed differential methylation and was further investigated in 228 children. Adjusting for confounders, urinary BPA glucuronide (BPAG) level inversely correlated with MAPK1 promoter methylation (β = −0.539, p = 0.010). For the logistic regression analysis, MAPK1 methylation status was dichotomized into higher methylated and lower methylated groups with cut off continuous variable of median of promoter methylation percentage (50%) while performing the analysis. MAPK1 methylation was lower in children with asthma than in children without asthma (mean ± SD; 69.82 ± 5.88% vs. 79.82 ± 5.56%) (p = 0.001). Mediation analysis suggested that MAPK1 methylation acts as a mediation variable between BPA exposure and asthma. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation.

Is carbohydrate-deficient transferrin in serum useful for detecting excessive alcohol consumption in hypertensive patients?

1994 ◽  
Vol 40 (11) ◽  
pp. 2057-2063 ◽  
Author(s):  
B Fagerberg ◽  
S Agewall ◽  
A Berglund ◽  
M Wysocki ◽  
P A Lundberg ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Intake ◽  
High Alcohol ◽  
Clinical Value ◽  
Excessive Alcohol Consumption ◽  
Cross Sectional ◽  
Hypertensive Patients ◽  
Carbohydrate Deficient Transferrin ◽  
Excessive Alcohol ◽  
High Alcohol Intake

Abstract The aim of this study was to examine the diagnostic usefulness of carbohydrate-deficient transferrin (CDT) in serum in a cross-sectional study of 439 treated hypertensive men. We related the results to alcohol intake by questionnaire and to biochemical and hemodynamic measurements known to reflect excessive alcohol consumption. The diagnostic sensitivity and the specificity for high alcohol intake (&gt; or = 24 g/day of ethanol) were 44% and 87%, respectively. The group with reported high alcohol intake (n = 32) was characterized by hemodynamic and biochemical changes typical of alcohol abuse. The corresponding profile for the patients with increased serum CDT concentrations (n = 70) was different in several respects, indicating a considerable number of false-positive tests. We conclude that serum CDT determination had low sensitivity and specificity for excessive alcohol consumption in this group of hypertensive patients. The results illustrate the importance of evaluating new laboratory methods in unselected patient populations before drawing any conclusions about their clinical value.

scholarly journals Alcohol consumption is associated with widespread changes in blood DNA methylation: Analysis of cross‐sectional and longitudinal data

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Pierre‐Antoine Dugué ◽  
Rory Wilson ◽  
Benjamin Lehne ◽  
Harindra Jayasekara ◽  
Xiaochuan Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alcohol Consumption ◽  
Longitudinal Data ◽  
Methylation Analysis ◽  
Cross Sectional ◽  
Dna Methylation Analysis

scholarly journals The Big Drink Debate: perceptions of the impact of price on alcohol consumption from a large scale cross-sectional convenience survey in north west England

2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Penny A Cook ◽  
Penelope A Phillips-Howard ◽  
Michela Morleo ◽  
Corinne Harkins ◽  
Linford Briant ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Large Scale ◽  
Cross Sectional ◽  
North West ◽  
The Impact

scholarly journals Contribution of Heritability and Epigenetic Factors to Skeletal Muscle Mass Variation in United Kingdom Twins

2016 ◽  
Vol 101 (6) ◽  
pp. 2450-2459 ◽  
Author(s):  
Gregory Livshits ◽  
Fei Gao ◽  
Ida Malkin ◽  
Maria Needhamsen ◽  
Yudong Xia ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
United Kingdom ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Decomposition Analysis ◽  
Repeated Measurements ◽  
Cross Sectional ◽  
Genome Wide ◽  
A Genome

Abstract Context: Skeletal muscle mass (SMM) is one of the major components of human body composition, with deviations from normal values often leading to sarcopenia. Objective: Our major aim was to conduct a genome-wide DNA methylation study in an attempt to identify potential genomic regions associated with SMM. Design: This was a mixed cross-sectional and longitudinal study. Setting: Community-based study. Participants: A total of 1550 middle-aged United Kingdom twins (monozygotic [MZ] and dizygotic [DZ]), 297 of which were repeatedly measured participated in the study. Main Outcome Measure: Appendicular lean mass assessed using dual-energy X-ray absorptiometry technology, and methylated DNA immunoprecipitation sequencing DNA methylation profiling genome-wide were obtained from each individual. Results: Heritability estimate of SMM, with simultaneous adjustment for covariates obtained using variance decomposition analysis, was h2 = 0.809 ± 0.050. After quality control and analysis of longitudinal stability, the DNA methylation data comprised of 723 029 genomic sites, with positive correlations between repeated measurements (Rrepeated = 0.114–0.905). Correlations between MZ and DZ twins were 0.51 and 0.38 at a genome-wide average, respectively, and clearly increased with Rrepeated. Testing for DNA methylation association with SMM in 50 discordant MZ twins revealed 36 081 nominally significant results, of which the top-ranked 134 signals (P &lt; .01 and Rrepeated &gt; 0.40) were subjected to replication in the sample of 1196 individuals. Seven SMM methylation association signals replicated at a false discovery rate less than 0.1, and these were located in or near genes DNAH12, CAND1, CYP4F29P, and ZFP64, which have previously been highlighted in muscle-related studies. Adjusting for age, smoking, and blood cell heterogeneity did not alter significance of these associations. Conclusion: This epigenome-wide study, testing longitudinally stable methylation sites, discovered and replicated a number of associations between DNA methylation at CpG loci and SMM. Four replicated signals were related to genes with potential muscle functions, suggesting that the methylome of whole blood may be informative of SMM variation.

scholarly journals Smoking and blood DNA methylation: novel associations, replication of previous findings and assessment of reversibility

2019 ◽  
Author(s):  
Pierre-Antoine Dugué ◽  
Chol-Hee Jung ◽  
JiHoon E Joo ◽  
Xiaochuan Wang ◽  
Ee Ming Wong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Smoking History ◽  
Cross Sectional ◽  
Blood Samples ◽  
Cross Sectional Analysis ◽  
A Genome ◽  
Former Smokers ◽  
Sectional Analysis ◽  
Novel Associations ◽  
Smoking Index

ABSTRACTWe conducted a genome-wide association study of blood DNA methylation and smoking, attempted replication of previously discovered associations, and assessed the reversibility of smoking-associated methylation changes. DNA methylation was measured in baseline peripheral blood samples for 5,044 participants in the Melbourne Collaborative Cohort Study. For 1,032 participants, these measures were repeated using blood samples collected at follow-up, a median of 11 years later. A cross-sectional analysis of the association between smoking and DNA methylation and a longitudinal analysis of changes in smoking status and changes in DNA methylation were conducted. We used our cross-sectional analysis to replicate previously reported associations for current (N=3,327) and former (N=172) smoking. A comprehensive smoking index accounting for the bioactivity of smoking and several aspects of smoking history was constructed to assess the reversibility of smoking-induced methylation changes. We identified 4,496 cross-sectional associations at P<10−7, including 3,296 that were novel. We replicated the majority (90%) of previously reported associations for current and former smokers. In our data, we observed for former smokers a substantial degree of return to the methylation levels of never smokers, compared with current smokers (median: 74%, IQR=63-86%). Consistent with this, we found wide-ranging estimates for the half-life parameter of the comprehensive smoking index. Longitudinal analyses identified 368 sites at which methylation changed upon smoking cessation. Our study provides evidence of many novel associations between smoking and DNA methylation at CpGs across the genome, replicates the vast majority of previously reported associations, and indicates wide-ranging reversibility rates for smoking-induced methylation changes.

scholarly journals MODERATE, REGULAR ALCOHOL CONSUMPTION IS ASSOCIATED WITH HIGHER COGNITIVE FUNCTION IN OLDER COMMUNITY-DWELLING ADULTS

2016 ◽  
pp. 1-9
Author(s):  
E.T. Reas ◽  
G.A. Laughlin ◽  
D. Kritz-Silverstein ◽  
E. Barrett-Connor ◽  
L.K. McEvoy
Keyword(s):  
Cognitive Function ◽  
Alcohol Consumption ◽  
Sex Education ◽  
Visual Memory ◽  
Alcohol Intake ◽  
Neuropsychological Test ◽  
Community Dwelling ◽  
Cross Sectional ◽  
Frequency Of Alcohol Intake ◽  
Self Assessed Health

Background: Evidence suggests that moderate alcohol consumption may protect against cognitive decline and dementia. However, uncertainty remains over the patterns of drinking that are most beneficial. Objective: To examine associations between amount and frequency of alcohol consumption with multiple domains of cognitive function in a well-characterized cohort of older community-dwelling adults in southern California. Design: Observational, cross-sectional cohort study. Setting: A research visit between 1988-1992 in Rancho Bernardo, California. Participants: 1624 participants of the Rancho Bernardo Study (mean age ± SD = 73.2 ± 9.3 years). Measurements: Participants completed a neuropsychological test battery, self-administered questionnaires on alcohol consumption and lifestyle, and a clinical health evaluation. We classified participants according to average amount of alcohol intake into never, former, moderate, heavy and excessive drinkers, and according to frequency of alcohol intake, into non-drinkers, rare, infrequent, frequent and daily drinkers. We examined the association between alcohol intake and cognitive function, controlling for age, sex, education, exercise, smoking, waist-hip ratio, hypertension and self-assessed health. Results: Amount and frequency of alcohol intake were significantly associated with cognitive function, even after controlling for potentially related health and lifestyle variables. Global and executive function showed positive linear associations with amount and frequency of alcohol intake, whereas visual memory showed an inverted U-shaped association with alcohol intake, with better performance for moderate and infrequent drinkers than for non-drinkers, excessive drinkers or daily drinkers. Conclusions: In several cognitive domains, moderate, regular alcohol intake was associated with better cognitive function relative to not drinking or drinking less frequently. This suggests that beneficial cognitive effects of alcohol intake may be achieved with low levels of drinking that are unlikely to be associated with adverse effects in an aging population.

scholarly journals Premenstrual syndrome and alcohol consumption: a systematic review and meta-analysis

BMJ Open ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. e019490 ◽  
Author(s):  
María del Mar Fernández ◽  
Jurgita Saulyte ◽  
Hazel M Inskip ◽  
Bahi Takkouche
Keyword(s):  
Systematic Review ◽  
Alcohol Consumption ◽  
Premenstrual Syndrome ◽  
Alcohol Intake ◽  
Meta Analysis ◽  
Harmful Effect ◽  
Personal Contact ◽  
Bibliographic Databases ◽  
Moderate Increase ◽  
Cross Sectional

ObjectivePremenstrual syndrome (PMS) is a very common disorder worldwide which carries an important economic burden. We conducted a systematic review and a meta-analysis to assess the role of alcohol in the occurrence of PMS.MethodsWe searched MEDLINE, EMBASE, the five regional bibliographic databases of the WHO, the Proceedings database and the Open Access Thesis and Dissertations (OATD) from inception to May 2017. We also reviewed the references of every article retrieved and established personal contact with researchers to trace further publications or reports. We did not include any language limitations. Studies were included if: (1) they presented original data from cohort, case-control or cross-sectional studies, (2) PMS was clearly defined as the outcome of interest, (3) one of the exposure factors was alcohol consumption, (4) they provided estimates of odds ratios, relative risks, or any other effect measure and their confidence intervals, or enough data to calculate them.ResultsWe identified 39 studies of which 19 were eligible. Intake of alcohol was associated with a moderate increase in the risk of PMS (OR=1.45, 95% CI: 1.17 to 1.79). Heavy drinking yielded a larger increase in the risk than any drinking (OR=1.79, 95% CI: 1.39 to 2.32).DiscussionOur results suggest that alcohol intake presents a moderate association with PMS risk. Future studies should avoid cross-sectional designs and focus on determining whether there is a threshold of alcohol intake under which the harmful effect on PMS is non-existent.

scholarly journals Alcohol Consumption and Risk of Common Autoimmune Inflammatory Diseases—Evidence From a Large-Scale Genetic Analysis Totaling 1 Million Individuals

2021 ◽  
Vol 12 ◽  
Author(s):  
Xia Jiang ◽  
Zhaozhong Zhu ◽  
Ali Manouchehrinia ◽  
Tomas Olsson ◽  
Lars Alfredsson ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Lupus Erythematosus ◽  
Statistical Power ◽  
Large Scale ◽  
Alcohol Intake ◽  
Genome Wide Association Study ◽  
Causal Effect ◽  
Autoimmune Disorders ◽  
Excessive Drinking ◽  
Shared Genetic

Purpose: Observational studies have suggested a protective effect of alcohol intake with autoimmune disorders, which was not supported by Mendelian randomization (MR) analyses that used only a few (&lt;20) instrumental variables.Methods: We systemically interrogated a putative causal relationship between alcohol consumption and four common autoimmune disorders, using summary-level data from the largest genome-wide association study (GWAS) conducted on inflammatory bowel disease (IBD), rheumatoid arthritis (RA), multiple sclerosis (MS), and systemic lupus erythematosus (SLE). We quantified the genetic correlation to examine a shared genetic similarity. We constructed a strong instrument using 99 genetic variants associated with drinks per week and applied several two-sample MR methods. We additionally incorporated excessive drinking as reflected by alcohol use disorder identification test score.Results: We observed a negatively shared genetic basis between alcohol intake and autoimmune disorders, although none was significant (rg = −0.07 to −0.02). For most disorders, genetically predicted alcohol consumption was associated with a slightly (10–25%) decreased risk of onset, yet these associations were not significant. Meta-analyzing across RA, MS, and IBD, the three Th1-related disorders yielded to a marginally significantly reduced effect [OR = 0.70 (0.51–0.95), P = 0.02]. Excessive drinking did not appear to reduce the risk of autoimmune disorders.Conclusions: With its greatly augmented sample size and substantially improved statistical power, our MR study does not convincingly support a beneficial role of alcohol consumption in each individual autoimmune disorder. Future studies may be designed to replicate our findings and to understand a causal effect on disease prognosis.

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