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We first differentiated demographic histories characterized by long IBD-segments shared within populations (for example, recently isolated or practiced endogamy) from those characterized by large numbers of short IBD-segments (for example, a historical bottleneck). For individuals within the same cluster, we plotted the per-individual mean total length of IBD versus the mean number of IBD segments shared (Fig. 3), showing the overall distribution of such values across all clusters (Fig. 3, Left) and focusing on subbranches of related clusters (Fig. 3B). Generally, we confirm a broad south–north gradient of increasing haplotype sharing in Europe. Individuals of Finnish ancestry present some of the highest levels of within-population IBD sharing in our sample of European haplotypes and is predominated by sharing of short IBD-segments. These Finnish results are consistent with a historical bottleneck and previous genetic observations (38, 39), as well as one of the lowest estimated historical Ne in our analysis (Fig. 4) and average coordinates of the inbreeding coefficient that is the proportion of the genome covered by ROH > 1.5 Mb (FROH), and the inbreeding coefficient that is measured by the observed versus the number of expected homozyotes (FSNP) for the Finnish clusters (Fig. 5).
Although S Europe trends toward a larger historical effective population size (Ne) and low levels of haplotype sharing (e.g., within Italy), there are notable exceptions. Maltese genetic differentiation is expanded upon in IBD-segment analysis (Fig. 3) and agrees with previous IBD estimates from a smaller Maltese sample (40). Malta has a slightly lower average within-cluster total IBD length than Finland, although the average Maltese IBD-segment is longer (Malta IBD segment = 3.17 cM, Finland = 2.07 cM), suggesting a more recent source of this elevated sharing. These results are matched by low historical Ne. FROH and FSNP analysis show that autozygosity is consistent with a historically small Ne rather than consanguinity in Malta.
Within SE Europe, both Turkey and Cyrpus exhibit elevated haplotype sharing (Fig. 3), as well as a lower historical Ne (Fig. 4) and evidence of modest consanguinity (Fig. 5). The IBD sharing profile of the Albania and Greece cluster supports evidence of isolation, with elevated haplotype sharing that is equivalent to that found in northeastern Europe (Fig. 2). Albania and Greece also present a consistently lower Ne than Greece, and FROH/FSNP results are consistent with isolation. Elsewhere in SE Europe, we observe NW Balkans presenting slightly longer within-cluster IBD segments than NE Balkans, which is matched with a consistently lower Ne and elevated ROH—suggestive of a smaller population than the northeast of the Balkans or neighboring central Europe to the north. Interesting, we find that a subset of Spanish individuals who present elevated within-cluster IBD-segment sharing differ with those of most in Spain (Fig. 3). In a focused analysis (SI Appendix, Supplementary Data 9), we conclude that these represent a distinct community or population clustered with other Spanish individuals who nevertheless exhibit elevated haplotype sharing consistent with isolation. These individuals project from other Spanish individuals in PC six (SI Appendix, Supplementary Data 9) and when projected on top of Human Origin references project toward “Spanish North” or “Basque” references (SI Appendix, Fig. 4.2).
Continuing previous observations of elevated haplotype sharing in island populations, we confirm previous signatures of isolation in island communities in northern Britain and expand with more results. We observe increased haplotype sharing of the British archipelago communities of Orkney, the Channel Islands, and the Isle of Man (Fig. 3) that is consistent with previous observations from Orkney (2), showing results from the Channel Islands and expanding upon previous analyses of the Isle of Man (9). These footprints appear to be more pronounced in Orkney, with a smaller Ne 10 generations ago (Fig. 4), as well as slightly longer IBD segments than those shared within the Channel Islands (Orkney IBD segment = 2.18 cM, Channel Island segment = 1.86 cM, Isle of Man segment = 1.90 cM). While Icelandic individuals do not form a private cluster (Fig. 2), there is evidence of elevated IBD sharing consistent with previous observations of homogeneity (41). We observe an increase of the total length of IBD and number of IBD segments between “Norway” Icelanders (i.e., Icelandic individuals placed in the cluster Norway) (45.9 cM and 20 segments, respectively) compared to that observed between Norway Norwegians (22.6 cM and 14 segments). This difference was significant both for total length of IBD (Mann–Whitney U, P = 4.5 × 10−11) or number of segments (Mann–Whitney U, P = 1.1 × 10−10).
Lastly, in an analysis of country-of-birth versus PCA of genetic relationship matrices, and network-based clustering methods, we have identified a community of individuals sampled from the UKBB with evidence of Ashkenazi Jewish ancestry. An analysis of haplotype sharing patterns supports a population of increased haplotype sharing that is intermediate between our Finnish and Maltese profiles (Fig. 3), with a low historical Ne 30 generations ago that has expanded within the past 10 generations (Fig. 4) and an increase in homozygosity (Fig. 5). In a focused analysis, we show that this cluster contains two broad groups of individuals, as follows: one with elevated haplotype sharing, with more and longer IBD and ROH detected, and another with a mixture of ancestries reflective of individuals with a recent admixture outside of the community and a generally higher historical Ne. This cline of elevated haplotype sharing is captured by PC three of the PCA of the pbwt paint coancestry matrix.
