Nearly all subjects were born in Sardinia (5,857 [95%]) and, specifically, in the Ogliastra region (5,442 [89%]; Figure 1B shows the birth places of participants in the restricted geographical region). Emphasizing the stability of the population, all grandparents were born in Sardinia for 95% of participants (Figure 1C). The cohort is organized into multiple complex pedigrees. Information collected at recruitment allowed us to organize 5,610 individuals into 711 connected pedigrees, each up to five generations deep. The largest pedigree connects 625 phenotyped individuals. In total the sample includes 34,469 relative pairs, with an average kinship coefficient of 0.1628. These relative pairs include 4,933 sibling pairs, 180 half-sibling pairs, 4,014 first cousins, 4,256 parent–child pairs, 675 grandparent–grandchild pairs, and 6,400 avuncular pairs in addition to other more distant relatives. Our sample also includes 11 monozygotic twins (identified by genotyping approximately 10,000 single nucleotide polymorphisms in all individuals). Because monozygotic twins are often more similar to each other than predicted by a simple genetic model (even with genetic dominance included), we included only one individual from each of these twin pairs in the analysis reported below.
