(C) To determine the significance of an overlap with annotation X independent of a possibly colocalizing annotation Y, we partition each locus into two types of fragments: those regions mapped by Y sites (light blue blocks) and those that lack them (denoted as Y¯; white blocks). We join the respective Y and Y¯ fragments into two independent continuous segments. To generate the null distribution, we shift annotation X separately within each of the two segments. For each iteration, we count the proportion of loci where any of the linked SNPs overlaps annotation X in either Y or Y¯ segments to determine the significance of the observed overlap.