The first suggestion that linkage disequilibrium could account for associations between a genetic variant and a disease was made in 1972 in the context of the HLA association with Hodgkin's disease11. The overall data on the HLA and Hodgkin's disease association were already then—and remain—significant, although with low ORs. These data led to the explanation of how genetic marker associations with a disease could be due to variation in a gene closely linked to that giving rise to the observed disease association, by linkage disequilibrium. This was the origin of the idea of genetic marker and disease association studies, which have now become feasible on a large scale because of the huge range of SNPs now available at the DNA level, and because of the associated development of high-throughput technology.
