ArticleAlcoholism, clinical and experimental research2015
Combined Whole Methylome and Genomewide Association Study Implicates CNTN4 in Alcohol Use.
Article in Alcoholism, clinical and experimental research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.
- Genetic influences on alcohol flushing in East Asian populations.BMC genomics · 2023Pooled it
- A DNA methylation biomarker of alcohol consumption.Molecular psychiatry · 2018Pooled it
- Alcohol consumption and DNA methylation: an epigenome-wide association study within the French E3N cohort.Clinical epigenetics · 2025Article
- Proteomic changes upon treatment with semaglutide in individuals with obesity.Nature medicine · 2025Article
- Methylome-wide association studies of psychiatric disorders.EC psychology and psychiatry · 2024Article
- Epigenetic Biomarkers for Environmental Exposures and Personalized Breast Cancer Prevention.International journal of environmental research and public health · 2020Article
- Genetics of alcohol use disorder: a review.Current opinion in psychology · 2019Review
- Gene expression profiling in the human alcoholic brain.Neuropharmacology · 2017Review
- DNA methylation in the pathophysiology of hyperphenylalaninemia in the PAH(enu2) mouse model of phenylketonuria.Molecular genetics and metabolism · 2016Article
- Validation of differential GDAP1 DNA methylation in alcohol dependence and its potential function as a biomarker for disease severity and therapy outcome.Epigenetics · 2016Article
- Decoding the non-coding genome: elucidating genetic risk outside the coding genome.Genes, brain, and behavior · 2016Review
- Review
- Transcriptional Regulators as Targets for Alcohol Pharmacotherapies.Handbook of experimental pharmacologyArticle
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMethylome-wide association (MWAS) studies present a new way to advance the search for biological correlates for alcohol use. A challenge with methylation studies of alcohol involves the causal direction of significant methylation-alcohol associations. One way to address this issue is to combine MWAS data with genomewide association study (GWAS) data.
methodsHere, we combined MWAS and GWAS results for alcohol use from 619 individuals. Our MWAS data were generated by next-generation sequencing of the methylated genomic DNA fraction, producing over 60 million reads per subject to interrogate methylation levels at ~27 million autosomal CpG sites in the human genome. Our GWAS included 5,571,786 single nucleotide polymorphisms (SNPs) imputed with 1000 Genomes.
resultsWhen combining the MWAS and GWAS data, our top finding was a region in an intron of CNTN4 (p = 2.55 × 10(-8) ), located between chr3: 2,555,403 and 2,555,524, encompassing SNPs rs1382874 and rs1382875. This finding was then replicated in an independent sample of 730 individuals. We used bisulfite pyrosequencing to measure methylation and found significant association with regular alcohol use in the same direction as the MWAS (p = 0.021). Rs1382874 and rs1382875 were genotyped and found to be associated in the same direction as the GWAS (p = 0.008 and p = 0.009). After integrating the MWAS and GWAS findings from the replication sample, we replicated our combined analysis finding (p = 0.0017) in CNTN4.
conclusionsThrough combining methylation and SNP data, we have identified CNTN4 as a risk factor for regular alcohol use.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.