Figure 1. Example of linked disease markers with no association. The diagram illustrates the scenario where common variants can be linked along a haplotype within families but will not be identified by an association study. Here, we place theoretical disease variants Z1, Z2, and Z3 in families 1, 2, and 3, respectively. We assume that the disease-causing variants Z are rare and are not genotyped. Markers A, B, C, and D are assumed to have a common minor allele frequency (MAF) and have been genotyped. All four markers are also located on the same haplotype close to each other, so that it is unlikely any crossing over will occur within families. Looking within each family, it is clear that all markers are linked to the disease marker because in each family the black haplotype cosegregates with the disease phenotype. However, looking across each family, A, B, C, and D are not associated with the disease phenotype, because both alleles of each marker are present in affected and unaffected individuals.