Abstract
Alcohol consumption can increase the risk of chronic diseases, such as myocardial infarction, coronary artery disease, hyperlipidemia, and hypertension. We aimed to assess the association between genotype, DNA methylation patterns, alcohol consumption, and chronic diseases in Korean population. We analyzed 8840 subjects for genotypes and 446 for DNA methylation among the 9351 subjects from the Korean Genome and Epidemiology Study (KoGES). We further divided both groups into two sub-groups according to the presence/absence of chronic diseases. We selected genes whose methylation varied significantly with alcohol consumption, and visualized genotype and DNA methylation patterns specific to each group. Genome-wide association study (GWAS) revealed single nucleotide polymorphisms (SNPs) rs2074356 and rs11066280 in HECT domain E3 ubiquitin protein ligase 4 (HECTD4) to be significantly associated with alcohol consumption in both the presence. The rs12229654 genotype also displayed significantly different patterns with alcohol consumption. Furthermore, we retrieved differentially methylated regions (DMRs) from four groups based on sex and chronic diseases and compared them by drinking status. In genotype analysis, cardiovascular diseases (CVDs) showed a higher proportion in drinker than in non-drinker, but not in DMR analysis. Additionally, we analyzed the enriched Gene Ontology terms and Kyoto Gene and Genome Encyclopedia (KEGG) pathways and visualized the network, heatmap, and upset plot. We show that the pattern of DNA methylation associated with CVD is strongly influenced by alcoholism. Overall, this study identified genetic and epigenetic variants influenced by alcohol consumption and chronic diseases.
Highlights
The Genome-wide association study (GWAS) was performed on 8468 subjects, which is the intersection of 8840 subjects whose genotype was analyzed and 8953 subjects with no missing values in the five variables
DNA methylation analysis was performed on 423 subjects, which is the intersection of 446 subjects whose methylation patterns was analyzed and 8953 subjects with no missing values in the five variables
We show that genetic variation in HECT domain E3 ubiquitin protein ligase 4 (HECTD4) is associated with cardiovascular diseases (CVDs) risk in the presence and absence of alcoholism and that alcoholism significantly influences the pattern of differentially methylated regions (DMRs) methylation associated with CVD in DNA prepared from whole blood
Summary
Alcohol use disorder or alcoholism ranks sixth among factors that increase the risk of disease-related mortality and disability [1]. Alcoholism is a prevalent lifestyle factor relevant to chronic cardiovascular diseases (CVDs) such as myocardial infarction, coronary artery, hyperlipidemia, and hypertension [2]. The correlation between alcohol consumption and chronic diseases is well known, and restriction of alcohol intake is commonly recommended for the management of chronic diseases. Many studies have analyzed the association of alcohol-induced chronic diseases in preventive medicine and epidemiologic studies. A new approach based on omics data and data integration is required
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