Alcohol and nicotine codependence-associated DNA methylation changes in promoter regions of addiction-related genes.
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ABSTRACT:
SUBMITTER: Xu H
PROVIDER: S-EPMC5292964 | biostudies-literature | 2017 Feb
REPOSITORIES: biostudies-literature
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Alcohol and nicotine codependence-associated DNA methylation changes in promoter regions of addiction-related genes.
Xu Hongqin H Wang Fan F Kranzler Henry R HR Gelernter Joel J Zhang Huiping H
Scientific reports 20170206
Altered DNA methylation in addiction-related genes may modify the susceptibility to alcohol or drug dependence (AD or ND). We profiled peripheral blood DNA methylation levels of 384 CpGs in promoter regions of 82 addiction-related genes in 256 African Americans (AAs) (117 cases with AD-ND codependence and 139 controls) and 196 European Americans (103 cases with AD-ND codependence and 93 controls) using Illumina's GoldenGate DNA methylation array assays. AD-ND codependence-associated DNA methylat ...[more]
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Project description:Interaction of DNA methylation and sequence variants that are methylation quantitative trait loci (mQTLs) may influence susceptibility to diseases such as alcohol dependence (AD). We used genome-wide genotype data from 268 African Americans (AAs: 129 AD cases and 139 controls) and 143 European Americans (EAs: 129 AD cases and 14 controls) to identify mQTLs that were associated with promoter CpGs in 82 AD risk genes. 282 significant mQTL-CpG pairs (9.9 × 10(-100) ? P(nominal) ? 7.7 × 10(-8)) in AAs and 313 significant mQTL-CpG pairs (2.7 × 10(-53) ? P(nominal) ? 9.9 × 10(-8)) in EAs were identified [i.e., mQTL-CpG associations survived multiple-testing correction, q values (false discovery rate) ? 0.05]. The most significant mQTL was rs1800759, which was strongly associated with CpG cg12011299 in both AAs (P(nominal) = 9.9 × 10(-100); q = 6.7 × 10(-91)) and EAs (P(nominal) = 2.7 × 10(-53); q = 1.4 × 10(-44)). Rs1800759 (previously known to be associated to AD) and CpG cg12011299 (distance: 37 bp) are both located in alcohol dehydrogenase (ADH) 4 gene (ADH4) promoter region. In general, the strength of association between mQTLs and CpGs was inversely correlated with the distance between them. Association was also influenced by race and AD. Additionally, 48.3 % of the mQTLs identified in AAs and 65.6 % of the mQTLs identified in EAs were predicted to be expression QTLs. Three mQTLs (rs2173201, rs4147542, and rs4147541 in ADH1B-AHD1C gene cluster region) found in AAs were previously identified by our genome-wide association studies as being significantly associated with AD in AAs. Thus, DNA methylation, which can be influenced by sequence variants and is implicated in gene expression regulation, appears to at least partially underlie the association of genetic variation with AD.
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