Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism

Michael Osier, Andrew J. Pakstis, Judith R. Kidd, Jia Fu Lee, Shih Jiun Yin, Huei Chen Ko, Howard Edenberg, Ru Band Lu, Kenneth K. Kidd

Research output: Contribution to journalArticle

198 Citations (Scopus)

Abstract

Two of the three class I alcohol dehydrogenase (ADH) genes (ADH2 and ADH3) encode known functional variants that act on alcohol with different efficiencies. Variants at both these genes have been implicated in alcoholism in some populations because allele frequencies differ between alcoholics and controls. Specifically, controls have higher frequencies of the variants with higher V(max) (ADH2*2 and ADH3*1). In samples both of alcoholics and of controls from three Taiwanese populations (Chinese, Ami, and Atayal) we found significant pairwise disequilibrium for all comparisons of the two functional polymorphisms and a third, presumably neutral, intronic polymorphism in ADH2. The class I ADH genes all lie within 80 kb on chromosome 4; thus, variants are not inherited independently, and haplotypes must be analyzed when evaluating the risk of alcoholism. In the Taiwanese Chinese we found that, only among those chromosomes containing the ADH3*1 variant (high V(max)), the proportions of chromosomes with ADH2*1 (low V(max)) and those with ADH2*2 (high V(max)) are significantly different between alcoholics and controls (p < 10-5). The proportions of chromosomes with ADH3*1 and those with ADH3*2 are not significantly different between alcoholics and controls, on a constant ADH2 background (with ADH2*1, P = .83; with ADH2*2, P = .53). Thus, the observed differences in the frequency of the functional polymorphism at ADH3, between alcoholics and controls, can be accounted for by the disequilibrium with ADH2 in this population.

Original languageEnglish
Pages (from-to)1147-1157
Number of pages11
JournalAmerican Journal of Human Genetics
Volume64
Issue number4
DOIs
StatePublished - 1999

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Linkage Disequilibrium
Alcoholics
Alcoholism
Alcohol Dehydrogenase
Chromosomes
Population
Genes
Chromosomes, Human, Pair 4
Gene Frequency
Haplotypes
Alcohols

ASJC Scopus subject areas

  • Genetics

Cite this

Osier, M., Pakstis, A. J., Kidd, J. R., Lee, J. F., Yin, S. J., Ko, H. C., ... Kidd, K. K. (1999). Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism. American Journal of Human Genetics, 64(4), 1147-1157. https://doi.org/10.1086/302317

Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism. / Osier, Michael; Pakstis, Andrew J.; Kidd, Judith R.; Lee, Jia Fu; Yin, Shih Jiun; Ko, Huei Chen; Edenberg, Howard; Lu, Ru Band; Kidd, Kenneth K.

In: American Journal of Human Genetics, Vol. 64, No. 4, 1999, p. 1147-1157.

Research output: Contribution to journalArticle

Osier, M, Pakstis, AJ, Kidd, JR, Lee, JF, Yin, SJ, Ko, HC, Edenberg, H, Lu, RB & Kidd, KK 1999, 'Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism', American Journal of Human Genetics, vol. 64, no. 4, pp. 1147-1157. https://doi.org/10.1086/302317
Osier, Michael ; Pakstis, Andrew J. ; Kidd, Judith R. ; Lee, Jia Fu ; Yin, Shih Jiun ; Ko, Huei Chen ; Edenberg, Howard ; Lu, Ru Band ; Kidd, Kenneth K. / Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism. In: American Journal of Human Genetics. 1999 ; Vol. 64, No. 4. pp. 1147-1157.
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