Human Genetics

, Volume 132, Issue 6, pp 657–668 | Cite as

Extended genetic effects of ADH cluster genes on the risk of alcohol dependence: from GWAS to replication

  • Byung Lae Park
  • Jee Wook Kim
  • Hyun Sub Cheong
  • Lyoung Hyo Kim
  • Boung Chul Lee
  • Cheong Hoon Seo
  • Tae-Cheon Kang
  • Young-Woo Nam
  • Goon-Bo Kim
  • Hyoung Doo Shin
  • Ihn-Geun Choi
Original Investigation

Abstract

Alcohol dependence (AD) is a multifactorial and polygenic disorder involving complex gene-to-gene and gene-to-environment interactions. Several genome-wide association studies have reported numerous risk factors for AD, but replication results following these studies have been controversial. To identify new candidate genes, the present study used GWAS and replication studies in a Korean cohort with AD. Genome-wide association analysis revealed that two chromosome regions on Chr. 4q22-q23 (ADH gene cluster, including ADH5, ADH4, ADH6, ADH1A, ADH1B, and ADH7) and Chr. 12q24 (ALDH2) showed multiple association signals for the risk of AD. To investigate detailed genetic effects of these ADH genes on AD, a follow-up study of the ADH gene cluster on 4q22-q23 was performed. A total of 90 SNPs, including ADH1B rs1229984 (H47R), were genotyped in an additional 975 Korean subjects. In case–control analysis, ADH1Brs1229984 (H47R) showed the most significant association with the risk of AD (p = 2.63 × 10−21, OR = 2.35). Moreover, subsequent conditional analyses revealed that all positive associations of other ADH genes in the cluster disappeared, which suggested that ADH1Brs1229984 (H47R) might be the sole functional genetic marker across the ADH gene cluster. Our findings could provide additional information on the ADH gene cluster regarding the risk of AD, as well as a new and important insight into the genetic factors associated with AD.

Supplementary material

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Supplementary material 1 (XLS 100 kb)
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Supplementary material 2 (TIFF 3083 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Byung Lae Park
    • 1
  • Jee Wook Kim
    • 2
    • 3
  • Hyun Sub Cheong
    • 1
  • Lyoung Hyo Kim
    • 1
    • 7
  • Boung Chul Lee
    • 3
    • 4
  • Cheong Hoon Seo
    • 3
    • 5
  • Tae-Cheon Kang
    • 6
  • Young-Woo Nam
    • 7
  • Goon-Bo Kim
    • 7
  • Hyoung Doo Shin
    • 1
    • 7
  • Ihn-Geun Choi
    • 3
    • 8
  1. 1.Department of Genetic EpidemiologySNP Genetics Inc.SeoulRepublic of Korea
  2. 2.Department of NeuropsychiatryHallym University Dongtan Sacred Heart HospitalHwaseongRepublic of Korea
  3. 3.Hallym University Burn InstituteSeoulRepublic of Korea
  4. 4.Department of NeuropsychiatryHangang Sacred Heart Hospital, Hallym UniversitySeoulRepublic of Korea
  5. 5.Department of Rehabilitation MedicineHangang Sacred Heart Hospital, Hallym UniversitySeoulRepublic of Korea
  6. 6.Department of Anatomy and Neurobiology, Institute of Epilepsy ResearchHallym University, College of MedicineChuncheonRepublic of Korea
  7. 7.Department of Life ScienceSogang University, 1 Shinsu-dongSeoulRepublic of Korea
  8. 8.Department of NeuropsychiatryHallym University Kangnam Sacred Heart HospitalSeoulRepublic of Korea

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