Inferring genetic structure and ancestry using haplotype-based models, with applications to east and west African cohorts
By Dr Garrett Hellenthal
Garrett will describe statistical models his group and colleagues have developed to infer population structure, genetic ancestry, and to identify and date admixture events where different populations have intermixed, using autosomal Single-Nucleotide-Polymorphism data. In contrast to other commonly-used approaches, these techniques model associations among neighboring SNPs, i.e. haplotype information, which can increase the resolution of ancestral signals in certain cases.
He will illustrate these methods with an application to a cohort of more than 1100 Ethiopians from 69 ethnolinguistic groups. He will report the extent to which genetic similarity among Ethiopians correlates with birthplace, ethnic identity, shared language and the sharing of cultural practices. He will show how these approaches can distinguish whether observed (strong) genetic differences among groups are likely attributable to recent isolation or to ancient sub-structure. In particular he highlights a case study where a commonly-used clustering program ADMIXTURE gave misleading results when attempting to resolve a long-standing anthropological controversy involving the ancestral history of the Ethiopian Ari. In addition, by comparing Ethiopian haplotype patterns to those in people from 275 world-wide reference populations, we infer varying sources and dates of admixture across Ethiopia. These include admixture in Afroasiatic speakers dated to ~2800-3500 years ago related to sources similar to present-day Egyptians, and admixture in Nilo-Saharan speakers typically dated to less than 1100 years ago. They also show evidence of recent intermixing among previously separated Ethiopian groups, which is more prominent among geographically nearer populations and groups that share cultural traits in common.
Finally, he will report preliminary results on unpublished SNP data from Cameroon, Ghana and Nigeria. In particular, they show a strong correspondence between genetics and geography within Ghana, and significant sub-structure among Cameroonians living within 20km of one another. By cross-referencing our admixture inference with linguistic and archaeological records, they provide evidence for previously unreported climate-induced migrations occurring more than 3000 years ago, and intermixing related to historical empires.
Their findings emphasize the importance of denser sampling of people within geographic regions to recover a more refined picture of genetic structure and history, which may have implications for population stratification correction in genotype-phenotype association studies (i.e. GWAS). They also add to the growing list of examples indicating that most extant human populations show evidence of admixture events occurring within the last 4,000 years.
Authors: 1Garrett Hellenthal, 1Saioa Lopez, 1Nancy Bird, 2Ayele Tarekegn, 1Lucy van Dorp, 3Paschal Awah, 4Gavin Band, 2Endashaw Bekele, 5Roger Blench, 6Neil Bradman, 7Bruce Connell, 2Ephrem Mekonnen, 1Sam Morris, 8Nana Nketsia, 9Tamiru Oljira, 1Mark Thomas, 10Eno-Abasi Urua, 4David Zeitlyn
Author affiliations / organizations
1University College London, 2Addis Ababa University, 3University of Yaounde, 4University of Oxford, 5University of Cambridge, 6Henry Stewart Group, 7York University, 8Paramount Chief of Essikado, 9Ethiopian Biotechnology Institute, 10University of Uyo
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