Allelic association with SNPs: Metrics, populations, and the linkage disequilibrium map

Comparison of different metrics, using three large samples of haplotypes fr om different populations, demonstrates that rho is the most efficient measu re of association between pairs of single nucleotide polymorphisms (SNPs). Pairwise data can be modeled, using composite likelihood, to describe the d ecline in linkage disequilibrium with distance (the Malecot model). The evi dence from more isolated populations (Finland, Sardinia) suggests that link age disequilibrium extends to 427-893 kb but, even in samples representativ e of large heterogeneous populations, such as CEPH, the extent is 385 kb or seater. This suggests that isolated populations are not essential for link age disequilibrium mapping of common diseases with SNPs. The epsilon parame ter of the Malecot model (recombination and time), evaluated at each SNP, i ndicates regions of the genome with extensive and less extensive disequilib rium (low and high values of epsilon respectively). When plotted against th e physical may, the regions with extensive and less extensive linkage diseq uilibrium may correspond to recombination cold and hot spots, This is discu ssed in relation to the Xq25 cytogenetic band and the HFE gene region. Hum Mutat 17:255-262, 2001. (C) 2001 Wiley-Liss, Inc.