Figure 5.

Simulated Population and Ascertainment Fit to the Accumulation of First-Degree Relatedness in the DiscovEHR Cohort

The real data were calculated at periodic “freezes” indicated by punctuation points connected by the faint red line. Most simulation parameters were set on the basis of information about the real population demographics and the DiscovEHR ascertainment approach. However, two parameters were unknown and selected on the basis of their fit to the real data: (1) the effective population size from which samples were ascertained and (2) the increased chance that someone is ascertained given that a first-degree relative was previously ascertained, which we call “clustered ascertainment.” All panels show the same three simulated population sizes spanning the estimated effective population size. We simulated clustered ascertainment by randomly ascertaining an individual along with a Poisson-distributed random number of first-degree relatives (distributions’ lambdas are indicated in the legends).

(A) The accumulation of pairs of first-degree relatives as additional samples are ascertained.

(B) The proportion of the ascertained participants that have one or more first-degree relatives that have also been ascertained.

(C) Simulated ascertainment projections with upper and lower bounds of the number of first-degree relationships we expect with our current DiscovEHR ascertainment approach as we scale to our goal of 250K participants.

(D) Simulated projections with upper and lower bounds of the proportion of the ascertained participants that have one or more first-degree relatives that have also been ascertained.