Human Genetics

, Volume 132, Issue 7, pp 735–743

Association between common alcohol dehydrogenase gene (ADH) variants and schizophrenia and autism

  • Lingjun Zuo
  • Kesheng Wang
  • Xiang-Yang Zhang
  • Xinghua Pan
  • Guilin Wang
  • Yunlong Tan
  • Chunlong Zhong
  • John H. Krystal
  • Matthew State
  • Heping Zhang
  • Xingguang Luo
Original Investigation

Abstract

Humans express at least seven alcohol dehydrogenase (ADH) isoforms that are encoded by ADH gene cluster (ADH7ADH1CADH1BADH1AADH6ADH4ADH5) at chromosome 4. ADHs are key catabolic enzymes for retinol and ethanol. The functional ADH variants (mostly rare) have been implicated in alcoholism risk. In addition to catalyzing the oxidation of retinol and ethanol, ADHs may be involved in the metabolic pathways of several neurotransmitters that are implicated in the neurobiology of neuropsychiatric disorders. In the present study, we comprehensively examined the associations between common ADH variants [minor allele frequency (MAF) >0.05] and 11 neuropsychiatric and neurological disorders. A total of 50,063 subjects in 25 independent cohorts were analyzed. The entire ADH gene cluster was imputed across these 25 cohorts using the same reference panels. Association analyses were conducted, adjusting for multiple comparisons. We found 28 and 15 single nucleotide polymorphisms (SNPs), respectively, that were significantly associated with schizophrenia in African-Americans and autism in European-Americans after correction by false discovery rate (FDR) (q < 0.05); and 19 and 6 SNPs, respectively, that were significantly associated with these two disorders after region-wide correction by SNPSpD (8.9 × 10−5 ≤  ≤ 0.0003 and 2.4 × 10−5 ≤ p ≤ 0.0003, respectively). No variants were significantly associated with the other nine neuropsychiatric disorders, including alcohol dependence. We concluded that common ADH variants conferred risk for both schizophrenia in African-Americans and autism in European-Americans.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Lingjun Zuo
    • 1
  • Kesheng Wang
    • 2
  • Xiang-Yang Zhang
    • 3
  • Xinghua Pan
    • 4
  • Guilin Wang
    • 5
  • Yunlong Tan
    • 6
  • Chunlong Zhong
    • 7
  • John H. Krystal
    • 1
  • Matthew State
    • 1
  • Heping Zhang
    • 8
  • Xingguang Luo
    • 1
  1. 1.Department of PsychiatryYale University School of MedicineNew HavenUSA
  2. 2.Department of Biostatistics and EpidemiologyCollege of Public Health, East Tennessee State UniversityJohnson CityUSA
  3. 3.Menninger Department of Psychiatry and Behavioral SciencesBaylor College of MedicineHoustonUSA
  4. 4.Department of GeneticsYale University School of MedicineNew HavenUSA
  5. 5.Yale Center for Genome AnalysisYale University School of MedicineOrangeUSA
  6. 6.Biological Psychiatry Research Center, Beijing Huilongguan HospitalBeijingChina
  7. 7.Department of NeurologyRenji Hospital, Shanghai Jiaotong UniversityShanghaiChina
  8. 8.Department of BiostatisticsYale University School of Epidemiology and Public HealthNew HavenUSA

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