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

There has been considerable recent debate concerning the distances over whi ch revels of allelic association useful for genomic quantitative trait locu s (QTL) scans can be detected. We have examined simple sequence repeat (SSR ) polymorphisms and two single nucleotide polymorphisms (SNPs) in the regio n flanking the aldehyde dehydrogenase 2 locus, ALDH2, in populations of Jap anese alcoholics and controls. These groups differ significantly in the all ele frequencies for the functional SNP in exon XII of this gene located on chromosome 12. The results obtained with SSR markers complement recent inve stigations with SNPs over similar distances at the TCR alpha/delta locus. S ignificant 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 th e distance over which LD at this locus could be detected by an order of mag nitude. Furthermore, as a proof of principle, we show that comparisons of a llele frequency differences for the SSR markers in the case (alcoholics) an d control populations would have detected the ALDH2 marker as a putative QT L. Extending the tests to include alleles at two or three flanking loci sug gests that the power to detect QTLs through association can be enhanced sig nificantly.