Abstract
Alcohol response is a genetically influenced trait, and there is significant variation in the patterns of alcohol consumption between Māori and Caucasians in New Zealand. Previous studies have found that a variant of the alcohol dehydrogenase (ADH) gene (ADH1B*47His) is associated with protection against alcohol dependence in Māori. Here we extend our investigation of the ADH genes, hypothesising a different haplotype signature in Maori compared to Caucasians. We analysed nine single nucleotide polymorphisms (SNPs) spanning a 500-kb region on chromosome 4q surrounding the ADH1B variant and several other alcohol-metabolising genes (ADH 4, 5, 6, 7). Genotyping was carried out on 47 unrelated Māori individuals, and allele frequencies were compared to the Caucasian population. Large differences in minor allele frequencies were observed between Māori and Caucasian populations for six SNPs (P < 0.01). There was also strong linkage disequilibrium (LD) observed among SNP alleles in Maori indicating the presence of extended ancestral haplotype blocks (P < 0.01). Our results suggest that the Māori population has a different haplotype signature at the ADH gene region compared to Caucasians. These findings probably reflect the unique gene flow history of this genomic region in Maori and should be beneficial for designing future genetic association studies of alcohol-response traits and associated disorders in Polynesians.
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- NZ:
-
New Zealand
- ADH:
-
Alcohol dehydrogenase
- SNP:
-
Single nucleotide polymorphism
- LD:
-
Linkage disequilibrium
- MAF:
-
Minor allele frequency
References
Buetow KH, Edmonson M, MacDonald R, Clifford R, Yip P, Kelley J, Little DP, Strausberg R, Koester H, Cantor CR, Braun A (2001) High-throughput development and characterization of a genomewide collection of gene-based single nucleotide polymorphism markers by chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Proc Natl Acad Sci USA 98:581–584
Chambers GK, Day DJ, Marshall SJ, Robinson GM (2002a) Alcohol dependence: advances in understanding, diagnosis and treatment. N Z Sci Rev 59:35–41
Chambers GK, Marshall SJ, Robinson GM, Maguire S, Newton-Howes J, Chong NL (2002b) The genetics of alcoholism in Polynesians: alcohol and aldehyde dehydrogenase genotypes in young men. Alcohol Clin Exp Res 26:949–955
Chen WJ, Loh EW, Hsu YPP, Cheng ATA (1997) Alcohol dehydrogenase and aldehyde dehydrogenase genotypes and alcoholism among Taiwanese aborigines. Biol Psychiatry 41:703–709
Edenberg HJ, Xuei X, Chen HJ, Tian H, Wetherill LF, Dick DM, Almasy L, Bierut L, Bucholz KK, Goate A, Hesselbrock V, Kuperman S, Nurnberger J, Porjesz B, Rice J, Schuckit M, Tischfield J, Begleiter H, Foroud T (2006) Association of alcohol dehydrogenase genes with alcohol dependence: a comprehensive analysis. Hum Mol Genet 15:1539–1549
The International HapMap Consortium (2005) A haplotype map of the human genome. Nature 437:1299–1320
Marshall SJ, Whyte ALH, Hamilton JF, Chambers GK (2005) Austronesian prehistory and polynesian genetics: a molecular view of human migration across the Pacific. N Z Sci Rev 62:75–80
OpenOffice.org (2006) [Computer program] Version 2.0.3. OpenOffice.org: free office suite. http://www.openoffice.org/
Osier MV, Pakstis AJ, Soodyall H, Comas D, Goldman D, Odunsi A, Okonofua F, Parnas J, Schulz LO, Bertranpetit J, Bonne-Tamir B, Lu RB, Kidd JR, Kidd KK (2002) A global perspective on genetic variation at the ADH genes reveals unusual pattern of linkage disequilibrium and diversity. Am J Hum Genet 71:84–99
Rajeevan H, Osier MV, Cheung KH, Deng H, Druskin L, Heinzen R, Kidd JR, Stein S, Pakstis AJ, Tosches NP, Yeh CC, Miller PL, Kidd KK (2003) Alfred—the allele frequency database—update. Nucleic Acids Res 31:270–271
Thomasson HR, Crabb DW, Edenberg HJ, Li T-K (1993) Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism. Behav Genet 23:131–136
Acknowledgements
This project was supported by funds from the New Zealand Alcohol Advisory Council, Wellington Medical Research Foundation and Environmental Science and Research Ltd.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hall, D.A., Chambers, G.K. & Lea, R.A. Haplotype analysis at the alcohol dehydrogenase gene region in New Zealand Māori. J Hum Genet 52, 191–194 (2007). https://doi.org/10.1007/s10038-006-0094-1
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1007/s10038-006-0094-1
Keywords
This article is cited by
-
A unique demographic history exists for the MAO-A gene in Polynesians
Journal of Human Genetics (2012)