To provide a comprehensive assessment of the accuracy of methods we analysed eight different cohorts that vary in the extent of the relatedness between individuals. The cohorts are summarised in Table S1, six of these are considered to be from isolated populations. The Orkney Complex Disease Study (ORCADES) is an ongoing study in the isolated Scottish archipelago of Orkney [27]. The CROATIA-VIS (Vis) and CROATIA-KORCULA (Korcula) studies contain individuals recruited from the Dalmation islands of Vis and Korcula [27], [28]. The INGI-Val Borbera population is a collection of 1,664 genotyped individuals collected in the Val Borbera region, a geographically isolated valley located within the Appennine Mountains in Northwest Italy. The valley is inhabited by about 3,000 descendants from the original population, living in seven villages along the valley and in the mountains [29]. The INGI-FVG Cohort is a collection of six different isolated villages in the Friuli Venezia Giulia region of northern Italy [30]. The INGI-CARL cohort contains individuals from Carlantino, a small isolated village in the province of Foggia in southern Italy [30]. The CROATIA-Split (Split) cohort contains individuals