Distribution of local ancestry and evidence of adaptation in admixed populations

Rodrigo Secolin,Marilza L Santos,Tânia K De Araujo,Benilton S Carvalho,Cristiane S Rocha,Lara R Arauna,Fernando Cendes,Fábio R Torres,David Comas,Iscia Lopes-Cendes,Alex Mas-Sandoval

doi:10.1038/s41598-019-50362-2

Abstract

Admixed American populations have different global proportions of European, Sub-Saharan African, and Native-American ancestry. However, individuals who display the same global ancestry could exhibit remarkable differences in the distribution of local ancestry blocks. We studied for the first time the distribution of local ancestry across the genome of 264 Brazilian admixed individuals, ascertained within the scope of the Brazilian Initiative on Precision Medicine. We found a decreased proportion of European ancestry together with an excess of Native-American ancestry on chromosome 8p23.1 and showed that this is due to haplotypes created by chromosomal inversion events. Furthermore, Brazilian non-inverted haplotypes were more similar to Native-American haplotypes than to European haplotypes, in contrast to what was found in other American admixed populations. We also identified signals of recent positive selection on chromosome 8p23.1, and one gene within this locus, PPP1R3B, is related to glycogenesis and has been associated with an increased risk of type 2 diabetes and obesity. These findings point to a selection event after admixture, which is still not entirely understood in recent admixture events.

Highlights

Population structure due to genetic ancestry has been a significant confounding factor in genome-wide association studies (GWAS)[1] since it can potentially lead to results that are not replicated among different populations[2,3,4]
(1 KGP) populations (Fig. 1a and Supplementary Fig. 1), Brazilian-São Paulo sample (BRS) individuals were spread between Europeans, sub-Saharan Africans, and Native-Americans/East Asians, as are other admixed American populations, but were distributed mainly between Europeans and sub-Saharans rather than towards Native-Americans
Local ancestry information is available for admixed American populations[9], it is still poorly explored in Brazilian individuals[20]

Summary

Introduction

Population structure due to genetic ancestry has been a significant confounding factor in genome-wide association studies (GWAS)[1] since it can potentially lead to results that are not replicated among different populations[2,3,4]. Local ancestry inference has been poorly explored in Brazilian individuals[20], and since a specific demographic history can impact human populations differently, their study could potentially add relevant information about the distribution of local ancestry along the human genome. Present deviations, which can be due to the lack of methodological power to discriminate between two different ancestries in local ancestry inference, genetic drift after the admixture, or signals of recent natural selection[24,25,26]. If deviations in local ancestry are found beyond chance, we aim to explore the issue further by searching for signals of recent natural selection and the possibility of association with disease

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Results

Conclusion