In Figure 2, beginning with the single nucleotide polymorphism 922, the vertical lines represent successive mutation events in the parent sequence that create branch points in the phylogenetic tree. The 2 alleles of the single nucleotide polymorphism, 922, most effectively distinguish the 2 main branches of the phylogenetic tree; the A allele is shared by all sequences in clade A and the G allele is shared by all sequences in clade B. This is an unrooted phylogenetic tree; it has not been rooted by including an obvious ancestral sequence that would help to determine the absolute chronology of mutational events. Therefore, in this article, use of terms that imply timing refer to the apparent order of events according to this tree structure and not the absolute timing of mutational events. However, even in the absence of absolute chronology, comparison of divergent clades that enrich for a phenotypic variable, such as age at LOAD onset, provides an opportunity to screen the clades for mutations related to that disease. Some of the branch-point mutations of the phylogeny are unique to the subsequent branch (clade) and can be used to differentiate one clade from the other, whereas other mutations appear in more than 1 branch of the tree. Each horizontal line in Figure 2 indicates a sequence and a stack of horizontal lines indicates a sequence that is shared by multiple individuals. Figure 2 illustrates the point that mutations occur on chromosomes in the context of earlier mutations, giving rise to sequence diversity even within regions of strong LD. The ovals in Figure 2A enclose mutations that introduce sequence diversity and divide the population into related, but distinct, clades. Terminal clades are enclosed by boxes in Figure 2B. Each terminal clade has a differential mutational history. Identifying a collection of phased mutations or polymorphisms within a region of strong LD, as represented in Figure 2, typically exceeds the capacity of genome-wide association studies. In addition, because many of these multiple mutations are uncommon, they are not adequately assayed in genome-wide association studies.