title: Association between common alcohol dehydrogenase gene (ADH) variants and schizophrenia and autism.
abstract: Humans express at least seven alcohol dehydrogenase (ADH) isoforms that are encoded by ADH gene cluster (ADH7-ADH1C-ADH1B-ADH1A-ADH6-ADH4-ADH5) 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) ≤ p ≤ 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.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06516, USA. Lingjun.Zuo@yale.edu
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zuo
authors.forename: Kesheng
authors.initials: K
authors.lastname: Wang
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Zhang
authors.forename: Xinghua
authors.initials: X
authors.lastname: Pan
authors.forename: Guilin
authors.initials: G
authors.lastname: Wang
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Tan
authors.forename: Chunlong
authors.initials: C
authors.lastname: Zhong
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.forename: Matthew
authors.initials: M
authors.lastname: State
authors.forename: Heping
authors.initials: H
authors.lastname: Zhang
authors.forename: Xingguang
authors.initials: X
authors.lastname: Luo
mesh_terms: D000328:Adult; D001741:Black or African American; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D001321:Autistic Disorder / Q000201:enzymology / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics*; D044465:White People
chemical_list: D000426:Alcohol Dehydrogenase