In these analyses, we used 39,722 unrelated individuals that had provided consent for population genetics research. Each individual was grouped into their TOPMed study, except for individuals from the AFGen project, which were treated as one study (Extended Data Tables 1, 2). Individuals from the FHS and ARIC projects individuals, which overlapped with the AFGen project, remained in their respective studies and were not grouped into the AFGen project. Individuals for whom the population group was either missing or ‘other’ were removed from the analysis. We then removed all indels, multi-allelic variants and singletons from the remaining 39,168 individuals. Each study was then split by population group. We excluded studies that had fewer than 19 samples from the analysis; however all 39,168 samples were used to define singleton filtering. We used the Jaccard index102, J, to determine the intersection of rare variants (2 ≤ sample count ≤ 100) between two individuals divided by the union of the rare variants of that pair, where the sample count indicates the number of individuals with either a heterozygote or homozygote variant. We then determined the average J value between and within each study.
