Inferring Admixture Histories of Human Populations Using Linkage Disequilibrium

TL;DR

This paper introduces ALDER, a new LD-based method for inferring human population admixture times, proportions, and relationships, with improved robustness and applicability over previous approaches.

Contribution

The authors develop a versatile LD-based inference tool, including a new weighted LD statistic, three-population test, and methods for phylogenetic analysis, implemented in the ALDER software.

Findings

Successfully inferred admixture dates and proportions in diverse populations.

Identified admixture events undetectable by previous tests.

Revealed complex population relationships using LD curve comparisons.

Abstract

Long-range migrations and the resulting admixtures between populations have been important forces shaping human genetic diversity. Most existing methods for detecting and reconstructing historical admixture events are based on allele frequency divergences or patterns of ancestry segments in chromosomes of admixed individuals. An emerging new approach harnesses the exponential decay of admixture-induced linkage disequilibrium (LD) as a function of genetic distance. Here, we comprehensively develop LD-based inference into a versatile tool for investigating admixture. We present a new weighted LD statistic that can be used to infer mixture proportions as well as dates with fewer constraints on reference populations than previous methods. We define an LD-based three-population test for admixture and identify scenarios in which it can detect admixture events that previous formal tests cannot. We further show that we can uncover phylogenetic relationships among populations by comparing weighted LD curves obtained using a suite of references. Finally, we describe several improvements to the computation and fitting of weighted LD curves that greatly increase the robustness and speed of the calculations. We implement all of these advances in a software package, ALDER, which we validate in simulations and apply to test for admixture among all populations from the Human Genome Diversity Project (HGDP), highlighting insights into the admixture history of Central African Pygmies, Sardinians, and Japanese.