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Human Molecular Genetics, 2000, Vol. 9, No. 20 2993-2999
© 2000 Oxford University Press

Allele association studies with SSR and SNP markers at known physical distances within a 1 Mb region embracing the ALDH2 locus in the Japanese, demonstrates linkage disequilibrium extending up to 400 kb

H.G. Koch, J. McClay, E.-W. Loh, S. Higuchi1, J.-H. Zhao, P. Sham, D. Ball and I. W. Craig+

SGDP Research Centre, Institute of Psychiatry, Denmark Hill, London SE5 8AF, UK and 1Kurihama National Hospital, Kanagawa, Japan

There has been considerable recent debate concerning the distances over which levels of allelic association useful for genomic quantitative trait locus (QTL) scans can be detected. We have examined simple sequence repeat (SSR) polymorphisms and two single nucleotide polymorphisms (SNPs) in the region flanking the aldehyde dehydrogenase 2 locus, ALDH2, in populations of Japanese alcoholics and controls. These groups differ significantly in the allele frequencies for the functional SNP in exon XII of this gene located on chromosome 12. The results obtained with SSR markers complement recent investigations with SNPs over similar distances at the TCR {alpha}/{delta} locus. Significant allelic association with this marker could be detected for SSRs over distances up to 400 kb and over 37 kb for the SNP thereby extending the distance over which LD at this locus could be detected by an order of magnitude. Furthermore, as a proof of principle, we show that comparisons of allele frequency differences for the SSR markers in the case (alcoholics) and control populations would have detected the ALDH2 marker as a putative QTL. Extending the tests to include alleles at two or three flanking loci suggests that the power to detect QTLs through association can be enhanced significantly.

+ To whom correspondence should be addressed. Tel: +44 207 848 0018; Fax: +44 207 848 0407; Email: i.craig@iop.kcl.ac.uk


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