Fast model-based estimation of ancestry in unrelated individuals
Open accessAbstract
Population stratification has long been recognized as a confounding factor in genetic association studies. Estimated ancestries, derived from multi-locus genotype data, can be used to perform a statistical correction for population stratification. One popular technique for estimation of ancestry is the model-based approach embodied by the widely applied program structure . Another approach, implemented in the program EIGENSTRAT, relies on Principal Component Analysis rather than model-based estimation and does not directly deliver admixture fractions. EIGENSTRAT has gained in popularity in part owing to its remarkable speed in comparison to structure . We present a new algorithm and a program, ADMIXTURE, for model-based estimation of ancestry in unrelated individuals. ADMIXTURE adopts the likelihood model embedded in structure . However, ADMIXTURE runs considerably faster, solving problems in minutes that take structure hours. In many of our experiments, we have found that ADMIXTURE is almost as fast as EIGENSTRAT. The runtime improvements of ADMIXTURE rely on a fast block relaxation scheme using sequential quadratic programming for block updates, coupled with a novel quasi-Newton acceleration of convergence. Our algorithm also runs faster and with greater accuracy than the implementation of an Expectation-Maximization (EM) algorithm incorporated in the program FRAPPE. Our simulations show that ADMIXTURE's maximum likelihood estimates of the underlying admixture coefficients and ancestral allele frequencies are as accurate as structure 's Bayesian estimates. On real-world data sets, ADMIXTURE's estimates are directly comparable to those from structure and EIGENSTRAT. Taken together, our results show that ADMIXTURE's computational speed opens up the possibility of using a much larger set of markers in model-based ancestry estimation and that its estimates are suitable for use in correcting for population stratification in association studies.
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ADMIXTURE model-based clustering analyses produced results consistent with PCA in suggesting that individuals from the Levant_ChL population had a greater affinity on average to Iranian agriculturalist-related populations than was the case for earlier Levantine individuals.
“ADMIXTURE model-based clustering analyses34 produced results consistent with PCA in suggesting that individuals from the Levant_ChL population had a greater affinity on average to Iranian agriculturalist-related populations than was the case for earlier Levantine individuals.”
From Ancient DNA from Chalcolithic Israel reveals the role of population mixture in cultural transformation (2018) · cites this paper as [34]
ADMIXTURE reveals that the three ancient Egyptians differ from modern Egyptians by a relatively larger Near Eastern genetic component, in particular a component found in Neolithic Levantine ancient individuals.
“Model-based clustering using ADMIXTURE37 (Fig. 4b, Supplementary Fig. 4) further supports these results and reveals that the three ancient Egyptians differ from modern Egyptians by a relatively larger Near Eastern genetic component, in particular a component found in Neolithic Levantine ancient individuals36 (Fig. 4b).”
From Ancient Egyptian mummy genomes suggest an increase of Sub-Saharan African ancestry in post-Roman periods (2017) · cites this paper as [37]
Ancestry Composition estimates are highly concordant with ADMIXTURE estimates, with r2 values of 0.94, 0.98, and 0.91, for the three groups, respectively.
“Ancestry Composition estimates are highly concordant with ADMIXTURE66 estimates, with r2 values of 0.94, 0.98, and 0.91, for the three groups, respectively (Figure S14).”
From The genetic ancestry of African Americans, Latinos, and European Americans across the United States (2015) · cites this paper as [66]
Our estimates of low levels of African ancestry in European Americans are not the result of Ancestry Composition errors or biases, as validated by comparison to f4 statistics, 1000 Genomes Project consensus estimates, and ADMIXTURE estimates.
“To show that our estimates are not the result of Ancestry Composition errors or biases, we validated the estimates of low levels of African ancestry in European Americans comparing to f4 statistics,64 1000 Genomes Project consensus estimates,78 and ADMIXTURE estimates.66”
From The genetic ancestry of African Americans, Latinos, and European Americans across the United States (2015) · cites this paper as [66]
ADMIXTURE results replicate the findings from qpAdm for Sidon_BA and show mixture of Levant_N and ancient Iranian populations.
“The ADMIXTURE results replicate the findings from qpAdm for Sidon_BA and show mixture of Levant_N and ancient Iranian populations (Figure 3A).”
From Continuity and Admixture in the Last Five Millennia of Levantine History from Ancient Canaanite and Present-Day Lebanese Genome Sequences (2017) · cites this paper as [54]
The Discussion describes ADMIXTURE as ancestry-inference software, while the paper’s analyses concern HapMap3 and an inflammatory-bowel-disease dataset. Searches for Sidon_BA, qpAdm, Levant_N, and ancient Iranian populations found no passage addressing the claimed comparison or mixture; the paper’s Figure 3 concerns a different dataset. (LLM, conf=0.78)
Experimental — accuracy not yet measured
ADMIXTURE analysis was performed with five replicates for each k using random seeds, and the highest likelihood replicate was chosen.
“We performed five replicates for each k with random seeds and chose the highest likelihood replicate (fig. S3).”
From Ancient DNA sheds light on the genetic origins of early Iron Age Philistines (2019) · cites this paper as [23]
ADMIXTURE analysis reaffirmed the clustering and temporal shifts in affinity observed in the PCA visualization.
“These data were used in an ADMIXTURE analysis29, which reaffirmed the clustering and temporal shifts in affinity observed in the PCA visualization (Fig. 4).”
From Genome flux and stasis in a five millennium transect of European prehistory (2014) · cites this paper as [29]
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- Authors
- Alexander, D. H., Novembre, J., & Lange, K.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2009-07-31
- Volume
- 19
- Issue
- 9
- Pages
- 1655-1664
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC2752134
- OpenAlex
- W2119444539
- Cited by
- 9,898
- References
- 33
- Citations by year
- 2026: 1204 · 2025: 1315 · 2024: 1342 · 2023: 1024 · 2022: 1029 · 2021: 959 · 2020: 745 · 2019: 591 · 2018: 466 · 2017: 377 · 2016: 266 · 2015: 222 · 2014: 147 · 2013: 89 · 2012: 65
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (MH59490, GM53275)
- National Institute of Mental Health (R37MH059490, MH59490, R01MH059490)
- National Institute of General Medical Sciences (R01GM053275, GM 53275, T32GM008185)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- ancestry estimation, admixture, population stratification, model-based clustering, structure, sequential quadratic programming, genetic association studies, computational efficiency
- MeSH terms
- Algorithms, Europe, Gene Frequency, Genetics, Population, Genotype, Humans, Jews, Models, Genetic, Software, Time Factors, Inflammatory Bowel Diseases, Likelihood Functions, Computational Biology, Polymorphism, Single Nucleotide, Genetic Association Studies
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