Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Apr;193(4):1233-54.
doi: 10.1534/genetics.112.147330. Epub 2013 Feb 14.

Inferring admixture histories of human populations using linkage disequilibrium

Po-Ru Loh  1 , Mark Lipson, Nick Patterson, Priya Moorjani, Joseph K Pickrell, David Reich, Bonnie Berger
Affiliations

Inferring admixture histories of human populations using linkage disequilibrium

Po-Ru Loh et al. Genetics. 2013 Apr.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Notational diagram of phylogeny containing admixed population and references. Population C′ is descended from an admixture between A and B to form C; populations A′ and B′ are present-day references. In practice, we assume that postadmixture drift is negligible; i.e., the C–C′ branch is extremely short and C′ and C have identical allele frequencies. The branch points of A′ and B′ from the A–B lineage are marked A″ and B″; note that in a rooted phylogeny, these need not be most recent common ancestors (as in panel B; compare to panel A).
Figure 2
Figure 2
Dependence of date estimates and weighted LD amplitudes on fitting start point. Rows correspond to three test scenarios: simulated 75% YRI/25% CEU mixture 50 generations ago with Yoruba–French weights (A–C); Uygur with Han–French weights (D–F); HapMap Maasai with Yoruba–French weights (G–I). (A, D, and G) The weighted LD curve a^(d) (blue) with best-fit exponential decay curve (red), fit starting from d0 = 0.5 cM. The middle and right columns show the date estimate (B, E, H) and amplitude (C, F, I) as a function of d0. (We note that our date estimates for Uygur are somewhat more recent than those in Patterson et al. 2012, most likely because of our direct estimate of the affine term in the weighted LD curve.)
Figure 3
Figure 3
Weighted LD curves for Mbuti using San and Yoruba as reference populations (A) and using Mbuti itself as one reference and several different second references (B), and analogous curves for Biaka (C and D). Genetic distances are discretized into bins at 0.05 cM resolution. Data for each curve are plotted and fit starting from the corresponding ALDER-computed LD correlation thresholds. Different amplitudes of one-reference curves (B and D) imply different phylogenetic positions of the references relative to the true mixing populations (i.e., different split points Xi″), suggesting a sketch of a putative admixture graph (E). Relative branch lengths are qualitative, and the true root is not necessarily as depicted.
Figure 4
Figure 4
Weighted LD curves for HGDP Sardinian using Italian–Yoruba weights (A) and HapMap Japanese (JPT) using JPT itself as one reference and HapMap Han Chinese in Beijing (CHB) as the second reference (B). The exponential fits are performed starting at 1 cM and 1.2 cM, respectively, as selected by ALDER based on detected correlated LD.
Figure 5
Figure 5
Weighted LD curves for Onge using Onge itself as one reference and several different second references.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • The genetic history of Cochin Jews from India.
    Waldman YY, Biddanda A, Dubrovsky M, Campbell CL, Oddoux C, Friedman E, Atzmon G, Halperin E, Ostrer H, Keinan A. Waldman YY, et al. Hum Genet. 2016 Oct;135(10):1127-43. doi: 10.1007/s00439-016-1698-y. Epub 2016 Jul 4. Hum Genet. 2016. PMID: 27377974 Free PMC article.
  • The formation of human populations in South and Central Asia.
    Narasimhan VM, Patterson N, Moorjani P, Rohland N, Bernardos R, Mallick S, Lazaridis I, Nakatsuka N, Olalde I, Lipson M, Kim AM, Olivieri LM, Coppa A, Vidale M, Mallory J, Moiseyev V, Kitov E, Monge J, Adamski N, Alex N, Broomandkhoshbacht N, Candilio F, Callan K, Cheronet O, Culleton BJ, Ferry M, Fernandes D, Freilich S, Gamarra B, Gaudio D, Hajdinjak M, Harney É, Harper TK, Keating D, Lawson AM, Mah M, Mandl K, Michel M, Novak M, Oppenheimer J, Rai N, Sirak K, Slon V, Stewardson K, Zalzala F, Zhang Z, Akhatov G, Bagashev AN, Bagnera A, Baitanayev B, Bendezu-Sarmiento J, Bissembaev AA, Bonora GL, Chargynov TT, Chikisheva T, Dashkovskiy PK, Derevianko A, Dobeš M, Douka K, Dubova N, Duisengali MN, Enshin D, Epimakhov A, Fribus AV, Fuller D, Goryachev A, Gromov A, Grushin SP, Hanks B, Judd M, Kazizov E, Khokhlov A, Krygin AP, Kupriyanova E, Kuznetsov P, Luiselli D, Maksudov F, Mamedov AM, Mamirov TB, Meiklejohn C, Merrett DC, Micheli R, Mochalov O, Mustafokulov S, Nayak A, Pettener D, Potts R, Razhev D, Rykun M, Sarno S, Savenkova TM, Sikhymbaeva K, Slepchenko SM, Soltobaev OA, Stepanova N, Svyatko S, Tabaldiev K, Teschler-Nicola M, Tishkin AA, Tkachev VV, Vasilyev S, Velemínský P, … See abstract for full author list ➔ Narasimhan VM, et al. Science. 2019 Sep 6;365(6457):eaat7487. doi: 10.1126/science.aat7487. Science. 2019. PMID: 31488661 Free PMC article.
  • Revealing the impact of the Caucasus region on the genetic legacy of Romani people from genome-wide data.
    Bánfai Z, Ádám V, Pöstyéni E, Büki G, Czakó M, Miseta A, Melegh B. Bánfai Z, et al. PLoS One. 2018 Sep 10;13(9):e0202890. doi: 10.1371/journal.pone.0202890. eCollection 2018. PLoS One. 2018. PMID: 30199533 Free PMC article.
  • Genomic variation in baboons from central Mozambique unveils complex evolutionary relationships with other Papio species.
    Santander C, Molinaro L, Mutti G, Martínez FI, Mathe J, Ferreira da Silva MJ, Caldon M, Oteo-Garcia G, Aldeias V, Archer W, Bamford M, Biro D, Bobe R, Braun DR, Hammond P, Lüdecke T, Pinto MJ, Meira Paulo L, Stalmans M, Regala FT, Bertolini F, Moltke I, Raveane A, Pagani L, Carvalho S, Capelli C. Santander C, et al. BMC Ecol Evol. 2022 Apr 11;22(1):44. doi: 10.1186/s12862-022-01999-7. BMC Ecol Evol. 2022. PMID: 35410131 Free PMC article.
  • Unveiling the Genetic History of the Maniq, a Primary Hunter-Gatherer Society.
    Göllner T, Larena M, Kutanan W, Lukas H, Fieder M, Schaschl H. Göllner T, et al. Genome Biol Evol. 2022 Apr 10;14(4):evac021. doi: 10.1093/gbe/evac021. Genome Biol Evol. 2022. PMID: 35143674 Free PMC article.
See all "Cited by" articles

References

    1. Bramanti B., Thomas M., Haak W., Unterlaender M., Jores P., et al. , 2009. Genetic discontinuity between local hunter–gatherers and Central Europe’s first farmers. Science 326(5949): 137–140. - PubMed
    1. Chakraborty R., Weiss K., 1988. Admixture as a tool for finding linked genes and detecting that difference from allelic association between loci. Proc. Natl. Acad. Sci. USA 85(23): 9119–9123. - PMC - PubMed
    1. Chen G., Marjoram P., Wall J., 2009. Fast and flexible simulation of DNA sequence data. Genome Res. 19(1): 136–142. - PMC - PubMed
    1. Chikhi L., Bruford M., Beaumont M., 2001. Estimation of admixture proportions: a likelihood-based approach using Markov chain Monte Carlo. Genetics 158: 1347–1362. - PMC - PubMed
    1. Davies R., 1977. Hypothesis testing when a nuisance parameter is present only under the alternative. Biometrika 64(2): 247–254. - PubMed

Publication types