Clustering of 770,000 genomes reveals post-colonial population structure of North America

Abstract

Despite strides in characterizing human history from genetic polymorphism data, progress in identifying genetic signatures of recent demography has been limited. Here we identify very recent fine-scale population structure in North America from a network of over 500 million genetic (identity-by-descent, IBD) connections among 770,000 genotyped individuals of US origin. We detect densely connected clusters within the network and annotate these clusters using a database of over 20 million genealogical records. Recent population patterns captured by IBD clustering include immigrants such as Scandinavians and French Canadians; groups with continental admixture such as Puerto Ricans; settlers such as the Amish and Appalachians who experienced geographic or cultural isolation; and broad historical trends, including reduced north-south gene flow. Our results yield a detailed historical portrait of North America after European settlement and support substantial genetic heterogeneity in the United States beyond that uncovered by previous studies.

Towards a fine-scale population health monitoring system

“…We apply a framework to detect fine-scale population structure by characterizing a network of distant relatedness within patients in the BioMe biobank, and detect 17 distinct communities that are highly correlated with culturally endogamous groups and recent diaspora to New York City from countries around the world. We demonstrate that IBD community detection robustly and stably recapitulates recent patterns of demography in NYC, and similar ideas have been explored in previous work [32][33][34] . By linking to Electronic Health Records and testing for enrichment of health outcomes within uncovered communities, using phenotypes derived from ICD-9 and ICD-10 billing codes, we demonstrate a significant community-specific enrichment of both anticipated and novel health related traits.…”

“…A recent study of a direct-to-consumer genetic database of approximately 770,000 customers across the US also revealed myriad signatures of founder effects which could be attributed to both pre-diaspora population structure and/or post-diaspora isolation, i.e. multiple Irish ancestry groups in Boston 32 . This suggests that founder effects and founder populations may be more ubiquitous that previously thought, and that as yet little understood processes of diaspora and migration can contribute to these effects.…”

Personalized genealogical history inferred from biobank-scale IBD segments

“…Noting that this density of IBD segments is higher than that reported by existing studies 3 , we took extra caution assessing the quality of our results. Since quality assessment of IBD segment calls of a large cohort is a less-studied problem, we developed the following strategies: First, we compared the kinship coefficients derived from RaPID's IBD calls against a standard genotype-based relatedness caller, KING 4 .…”

Glioma risk associated with extent of estimated European genetic ancestry in African Americans and Hispanics

“…The overall proportion of EA varies substantially among individuals within these populations. [19][20][21][22] Over decades and centuries, chromosomes become mosaics of the ancestral chromosomes from which they arose. Patterns of continental ancestry can be examined both globally (averaged continental ancestry across the genome) and locally (probable continental origin of specific segments of DNA).…”