Figure 1.

Ascertaining a High Proportion of the Population in a Geographical Area Increases Family Structure and Impacts What Statistical-Analysis Approaches Should Be Used

(A) Traditional population-based studies (gray boxes) typically sample a small portion of individuals from several populations. HPG studies (green box) more densely sample individuals from one or more populations. Family-based studies (yellow box) heavily sample within extended families but do not sample nearly as many individuals as the other two study designs.

(B) The three study designs result in very different proportions of individuals in the cohort with one or more close relatives in the dataset.

(C) The three ascertainment approaches also result in very different amounts of family structure. Red and blue lines indicate first- and second-degree pairwise relationships, respectively. HPG studies are expected to contain a level of family structure between the other two designs.

(D) For this study, statistical-analysis approaches were binned into four categories on the basis of the level of family structure required to effectively use the approach. First column: “linkage” refers to traditional linkage analyses using one or more informative pedigrees; “pedigree-based analysis” refers to statistical methods beyond linkage that use pedigree structures within a larger cohort that includes unrelated individuals; “IBD modeling” refers to analyses that model the pairwise relationships between individuals without using the entire pedigree structure; “analysis of unrelateds” refers to analyses that assume all individuals in the cohort are unrelated. The amount of family structure impacts the approaches that can be used, and the arrows indicate the analysis ranges for which the three study designs are best suited.