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Genome-wide DNA methylation analysis in alcohol dependence

Authors

  • Ruiling Zhang,

    1. The 2nd Hospital affiliated to Xinxiang Medical University, Xinxiang City, Henan Province, China
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    • These two authors (Ruiling Zhang and Qin Miao) should be regarded as joint first authors.
  • Qin Miao,

    1. The 2nd Hospital affiliated to Xinxiang Medical University, Xinxiang City, Henan Province, China
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    • These two authors (Ruiling Zhang and Qin Miao) should be regarded as joint first authors.
  • Chuansheng Wang,

    1. The 2nd Hospital affiliated to Xinxiang Medical University, Xinxiang City, Henan Province, China
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  • Rongrong Zhao,

    1. The 2nd Hospital affiliated to Xinxiang Medical University, Xinxiang City, Henan Province, China
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  • Wenqiang Li,

    1. The 2nd Hospital affiliated to Xinxiang Medical University, Xinxiang City, Henan Province, China
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  • Colin N. Haile,

    1. Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA
    2. Michael E. DeBakey VA Medical Center, Houston, TX, USA
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  • Wei Hao,

    Corresponding author
    • The 2nd Hospital affiliated to Xinxiang Medical University, Xinxiang City, Henan Province, China
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  • Xiang Yang Zhang

    Corresponding author
    1. Michael E. DeBakey VA Medical Center, Houston, TX, USA
    2. Psychiatry Research Center, Beijing HuiLongGuan Hospital, Peking University, Beijing, China
    • Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA
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Correspondence to: Wei Hao, 2nd Hospital affiliated to Xinxiang Medical College, 388 Jianshe Road, Xinxiang, Henan Province, 453002, China. E-mail: weihao57@gmail.com and Xiang Yang Zhang, VA Medical Center, 2002 Holcombe Boulevard, Houston, Texas, 77030, USA. Email: xyzhang@bcm.edu

Abstract

Genetic, epigenetic, and environmental factors influence the development of alcohol dependence (AD). Recent studies have shown that DNA methylation markers in peripheral blood may serve as risk markers for AD. Yet a genome-wide epigenomic approach investigating the role of DNA methylation in AD has yet to be performed. We conducted a population-based, case-control study of genome-wide DNA methylation to determine if alterations in gene-specific methylation were associated with AD in a Chinese population. Using the Illumina Infinium Human Methylation27 BeadChip, we assessed gene-specific methylation in over 27 000 CpG sites from DNA isolated from lymphocytes in 63 male AD in-patients and 65 male healthy controls. Using a multi-factorial statistical model, we observed differential methylation between cases and controls at multiple CpG sites with the majority of the methylated CpG sites being hypomethylated. Analyses with the online gene set analysis toolkit WebGestalt revealed that the genes of interest were enriched in multiple biological processes involved in AD development. Gene Ontology function annotation showed that stress, immune response and signal transduction were highly associated with AD. Further analysis by the Kyoto Encyclopedia of Genes and Genomes revealed associations with multiple pathways involved in metabolism through cytochrome P450, cytokine–cytokine receptor interaction and calcium signaling. Associations with canonical pathways previously shown to be involved in AD were also observed, such as dehydrogenases 1A (ADH1A), ADH7, aldehyde dehydrogenases 3B2 (ALDH3B2) and cytochrome P450 2A13. We present evidence that alterations in DNA methylation may be associated with AD, which is consistent with epigenetic theory.

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