17AN EPIGENOME-WIDE ASSOCIATION STUDY (EWAS) OF ALCOHOL CONSUMPTION REVEALS DNA METHYLATION SIGNATURES OF ALCOHOL USE

2019 ◽  
Vol 29 ◽  
pp. S1075-S1076
Author(s):  
Toni Clarke ◽  
Stewart W. Morris ◽  
Rosie Walker ◽  
Heather Whalley ◽  
Kathryn Evans ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alcohol Consumption ◽  
Alcohol Use ◽  
Association Study

scholarly journals Epigenome-wide association study of alcohol consumption in N = 8161 individuals and relevance to alcohol use disorder pathophysiology: identification of the cystine/glutamate transporter SLC7A11 as a top target

2021 ◽  
Author(s):  
Falk W. Lohoff ◽  
Toni-Kim Clarke ◽  
Zachary A. Kaminsky ◽  
Rosie M. Walker ◽  
Mairead L. Bermingham ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Animal Models ◽  
Association Study ◽  
Cellular Response ◽  
Heavy Drinking ◽  
Glutamate Transporter ◽  
Postmortem Brain ◽  
Glutamate Signaling

AbstractAlcohol misuse is common in many societies worldwide and is associated with extensive morbidity and mortality, often leading to alcohol use disorders (AUD) and alcohol-related end-organ damage. The underlying mechanisms contributing to the development of AUD are largely unknown; however, growing evidence suggests that alcohol consumption is strongly associated with alterations in DNA methylation. Identification of alcohol-associated methylomic variation might provide novel insights into pathophysiology and novel treatment targets for AUD. Here we performed the largest single-cohort epigenome-wide association study (EWAS) of alcohol consumption to date (N = 8161) and cross-validated findings in AUD populations with relevant endophenotypes, as well as alcohol-related animal models. Results showed 2504 CpGs significantly associated with alcohol consumption (Bonferroni p value < 6.8 × 10−8) with the five leading probes located in SLC7A11 (p = 7.75 × 10−108), JDP2 (p = 1.44 × 10−56), GAS5 (p = 2.71 × 10−47), TRA2B (p = 3.54 × 10−42), and SLC43A1 (p = 1.18 × 10−40). Genes annotated to associated CpG sites are implicated in liver and brain function, the cellular response to alcohol and alcohol-associated diseases, including hypertension and Alzheimer’s disease. Two-sample Mendelian randomization confirmed the causal relationship of consumption on AUD risk (inverse variance weighted (IVW) p = 5.37 × 10−09). A methylation-based predictor of alcohol consumption was able to discriminate AUD cases in two independent cohorts (p = 6.32 × 10−38 and p = 5.41 × 10−14). The top EWAS probe cg06690548, located in the cystine/glutamate transporter SLC7A11, was replicated in an independent cohort of AUD and control participants (N = 615) and showed strong hypomethylation in AUD (p < 10−17). Decreased CpG methylation at this probe was consistently associated with clinical measures including increased heavy drinking days (p < 10−4), increased liver function enzymes (GGT (p = 1.03 × 10−21), ALT (p = 1.29 × 10−6), and AST (p = 1.97 × 10−8)) in individuals with AUD. Postmortem brain analyses documented increased SLC7A11 expression in the frontal cortex of individuals with AUD and animal models showed marked increased expression in liver, suggesting a mechanism by which alcohol leads to hypomethylation-induced overexpression of SLC7A11. Taken together, our EWAS discovery sample and subsequent validation of the top probe in AUD suggest a strong role of abnormal glutamate signaling mediated by methylomic variation in SLC7A11. Our data are intriguing given the prominent role of glutamate signaling in brain and liver and might provide an important target for therapeutic intervention.

scholarly journals An Exploratory Association Study of Alcohol Use Disorder and DNA Methylation

2016 ◽  
Vol 40 (8) ◽  
pp. 1633-1640 ◽  
Author(s):  
Sarah L. Hagerty ◽  
L. Cinnamon Bidwell ◽  
Nicole Harlaar ◽  
Kent E. Hutchison
Keyword(s):  
Dna Methylation ◽  
Alcohol Use ◽  
Association Study ◽  
Alcohol Use Disorder

scholarly journals Associations between alcohol use and accelerated biological ageing

2020 ◽  
Author(s):  
Sunniva M. K. Bøstrand ◽  
Kadi Vaher ◽  
Laura De Nooij ◽  
Mathew A. Harris ◽  
James H. Cole ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alcohol Consumption ◽  
Alcohol Use ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Positive Association ◽  
Biological Ageing ◽  
Age Related ◽  
Brain Ageing ◽  
Brain Age

AbstractBackgroundHarmful alcohol use is a leading cause of premature death, and is associated with age-related disease. Ageing is highly variable between individuals, and may deviate from chronological ageing, suggesting that biomarkers of biological ageing (based on DNA methylation or brain structural measures) may be clinically relevant. Here, we investigated the relationships between alcohol phenotypes and both brain and DNA methylation age estimates.MethodsFirst, using data from UK Biobank and Generation Scotland, we tested the association between alcohol consumption (units/week) or hazardous use (AUDIT scores), and accelerated brain and epigenetic ageing in 20,258 and 8,051 individuals, respectively. Second, we used Mendelian randomization to test for a causal effect of alcohol consumption levels and alcohol use disorder (AUD) on biological ageing.ResultsAlcohol use showed a consistent positive association with higher predicted brain age (AUDIT-C: β=0.053, p=3.16×10−13; AUDIT-P: β=0.052, p=1.6×10−13; total AUDIT score: β=0.062, p=5.52×10−16; units/week: β=0.078, p=2.20×10−16), and DNA methylation GrimAge (Units/week: β=0.053, p=1.48×10− 7) and PhenoAge (Units/week: β=0.077, p=2.18×10−10). Mendelian randomization analyses revealed some evidence for a causal effect of AUD on accelerated brain ageing (β=0.272, p=0.044), and no evidence for a causal effect of alcohol consumption levels on accelerated biological ageing.ConclusionsWe provide consistent phenotypic evidence linking alcohol use with accelerated biological ageing. There is possible evidence for a causal effect of AUD on brain age, but not for any other alcohol-related trait on brain or epigenetic age acceleration. Future studies investigating the mechanisms associating alcohol use with accelerated biological ageing are warranted.

scholarly journals Epigenome-wide association study of whole blood gene expression in Framingham Heart Study participants provides molecular insight into the potential role of CHRNA5 in cigarette smoking-related lung diseases

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chen Yao ◽  
Roby Joehanes ◽  
Rory Wilson ◽  
Toshiko Tanaka ◽  
Luigi Ferrucci ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Dna Methylation ◽  
Cigarette Smoking ◽  
Association Study ◽  
Whole Blood ◽  
Lung Diseases ◽  
Epigenetic Modification ◽  
Blood Gene Expression ◽  
Increased Risk

Abstract Background DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases. Results We performed an epigenome-wide association study of whole blood gene expression in ~ 6000 individuals from four cohorts. We discovered and replicated numerous CpGs associated with the expression of cis genes within 500 kb of each CpG, with 148 to 1,741 cis CpG-transcript pairs identified across cohorts. We found that the closer a CpG resided to a transcription start site, the larger its effect size, and that 36% of cis CpG-transcript pairs share the same causal genetic variant. Mendelian randomization analyses revealed that hypomethylation and lower expression of CHRNA5, which encodes a smoking-related nicotinic receptor, are causally linked to increased risk of COPD and lung cancer. This putatively causal relationship was further validated in lung tissue data. Conclusions Our results provide a large and comprehensive association study of whole blood DNA methylation with gene expression. Expression platform differences rather than population differences are critical to the replication of cis CpG-transcript pairs. The low reproducibility of trans CpG-transcript pairs suggests that DNA methylation regulates nearby rather than remote gene expression. The putatively causal roles of methylation and expression of CHRNA5 in relation to COPD and lung cancer provide evidence for a mechanistic link between patterns of smoking-related epigenetic variation and lung diseases, and highlight potential therapeutic targets for lung diseases and smoking cessation.

Cheers together, but not alone: Peer drinking moderates alcohol consumption following interpersonal stress

2021 ◽  
pp. 026540752199604
Author(s):  
Hannah R. Hamilton ◽  
Stephen Armeli ◽  
Howard Tennen
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Academic Stress ◽  
Interpersonal Stress ◽  
Need To Belong ◽  
Effective Strategy ◽  
Social Drinking ◽  
Interpersonal Stressors ◽  
Peer Drinking

In view of the importance of the need to belong in motivating behavior, we examined whether interpersonal and academic stress differentially influence social and solitary alcohol consumption and whether social and solitary alcohol consumption differentially predict next-day interpersonal and academic stress. Based on research suggesting that drinking with friends is related to increased alcohol consumption following belongingness threat, we also examined whether peer consumption moderates associations between daily interpersonal stress and social drinking. Each day for 30 days, 1641 undergraduates reported stress, alcohol consumption, and peer consumption. Academic stress was related to lower levels of social and solitary alcohol consumption. Interpersonal stress was associated with greater social alcohol consumption, but only when students reported being around others who were drinking greater than average peer quantities. However, although social drinking was related to lower next-day academic stress, it was unrelated to next-day interpersonal stress. Findings are consistent with the notion that individuals’ perceptions of peers’ alcohol use might serve as a signal to join in this behavior to reduce belongingness threats associated with interpersonal stressors, although this may not be an effective strategy.

Changes in DNA methylation persist over time in males with severe alcohol use disorder—A longitudinal follow‐up study

2021 ◽  
Author(s):  
Soundarya Soundararajan ◽  
Arpana Agrawal ◽  
Meera Purushottam ◽  
Shravanthi Daphne Anand ◽  
Bhagyalakshmi Shankarappa ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Follow Up Study ◽  
Over Time

scholarly journals Residential surrounding greenness and DNA methylation: An epigenome-wide association study

2021 ◽  
Vol 154 ◽  
pp. 106556
Author(s):  
Rongbin Xu ◽  
Shuai Li ◽  
Shanshan Li ◽  
Ee Ming Wong ◽  
Melissa C. Southey ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Association Study

scholarly journals A Genome-Wide Integrative Association Study of DNA Methylation and Gene Expression Data and Later Life Cognitive Functioning in Monozygotic Twins

2020 ◽  
Vol 14 ◽  
Author(s):  
Mette Soerensen ◽  
Dominika Marzena Hozakowska-Roszkowska ◽  
Marianne Nygaard ◽  
Martin J. Larsen ◽  
Veit Schwämmle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cognitive Functioning ◽  
Association Study ◽  
Gene Expression Data ◽  
Monozygotic Twins ◽  
Later Life ◽  
Expression Data ◽  
Genome Wide ◽  
A Genome

scholarly journals Alcohol Use Disorder among Patients Suffered from Road Collisions in a Vietnamese Delta Province

2019 ◽  
Vol 16 (13) ◽  
pp. 2423 ◽  
Author(s):  
Hai Minh Vu ◽  
Tung Thanh Tran ◽  
Giang Thu Vu ◽  
Cuong Tat Nguyen ◽  
Chau Minh Nguyen ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Drinking Behavior ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Problematic Drinking ◽  
Current Context ◽  
Educational Campaign ◽  
Causes Of Deaths ◽  
The Relationship

Traffic collisions have continuously been ranked amongst the top causes of deaths in Vietnam. In particular, drinking has been recognized as a major factor amplifying the likelihood of traffic collisions in various settings. This study aims to examine the relationship between alcohol use and traffic collisions in the current context of Vietnam. A cross-sectional study was conducted on 413 traffic collisions patients in six health facilities in the Thai Binh Province to investigate the level of alcohol consumption and identify factors influencing alcohol use among these patients. The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scale was used to determine the problematic drinking behavior of the participants. The percentage of patients having problematic drinking was more than 30%. Being male, having a high household income, and working as farmer/worker were risk factors for alcohol abuse. People causing accidents and patients with a traumatic brain injury had a higher likelihood of drinking alcohol before the accidents. This study highlights the necessity of more stringent laws on reducing drink-driving in Vietnam. In addition, more interventions, especially those utilizing mass media like educational campaign of good behavior on social networks, are necessary to reduce alcohol consumption in targeted populations in order to decrease the prevalence and burden of road injuries.

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