Population Structure and Eigenanalysis

Overview

Journal PLoS Genet

Specialty Genetics

Date 2006 Dec 30

PMID 17194218

Citations 2555

Authors

Nick Patterson

Alkes L Price

David Reich

Affiliations

Soon will be listed here.

Abstract

Current methods for inferring population structure from genetic data do not provide formal significance tests for population differentiation. We discuss an approach to studying population structure (principal components analysis) that was first applied to genetic data by Cavalli-Sforza and colleagues. We place the method on a solid statistical footing, using results from modern statistics to develop formal significance tests. We also uncover a general "phase change" phenomenon about the ability to detect structure in genetic data, which emerges from the statistical theory we use, and has an important implication for the ability to discover structure in genetic data: for a fixed but large dataset size, divergence between two populations (as measured, for example, by a statistic like FST) below a threshold is essentially undetectable, but a little above threshold, detection will be easy. This means that we can predict the dataset size needed to detect structure.

Citing Articles

High continuity of forager ancestry in the Neolithic period of the eastern Maghreb.

Lipson M, Ringbauer H, Lucarini G, Aouadi N, Aoudia L, Belhouchet L Nature. 2025; .

PMID: 40074896 DOI: 10.1038/s41586-025-08699-4.

Genome-Wide Association Study Identifying a Novel Gene Related to a History of Febrile Convulsions in Patients With Focal Epilepsy.

Kim J, Lee H, Park H, Lee J, Kim W J Clin Neurol. 2025; 21(2):123-130.

PMID: 40065453 PMC: 11896740. DOI: 10.3988/jcn.2024.0296.

Determining population structure from k-mer frequencies.

Hrytsenko Y, Daniels N, Schwartz R PeerJ. 2025; 13:e18939.

PMID: 40061228 PMC: 11890038. DOI: 10.7717/peerj.18939.

Convergent evolution of complex adaptive traits modulates angiogenesis in high-altitude Andean and Himalayan human populations.

Ferraretti G, Rill A, Abondio P, Smith K, Ojeda-Granados C, De Fanti S Commun Biol. 2025; 8(1):377.

PMID: 40050470 PMC: 11885840. DOI: 10.1038/s42003-025-07813-6.

Ancestral origins and post-admixture adaptive evolution of highland Tajiks.

Wen J, Liu J, Feng Q, Lu Y, Yuan K, Zhang X Natl Sci Rev. 2025; 11(9):nwae284.

PMID: 40040643 PMC: 11879426. DOI: 10.1093/nsr/nwae284.

References

Balding D, Nichols R . A method for quantifying differentiation between populations at multi-allelic loci and its implications for investigating identity and paternity. Genetica. 1995; 96(1-2):3-12. DOI: 10.1007/BF01441146. View

Spielman R, McGinnis R, Ewens W . Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 1993; 52(3):506-16. PMC: 1682161. View

Patterson N, Hattangadi N, Lane B, Lohmueller K, Hafler D, Oksenberg J . Methods for high-density admixture mapping of disease genes. Am J Hum Genet. 2004; 74(5):979-1000. PMC: 1181990. DOI: 10.1086/420871. View

Hoggart C, Shriver M, Kittles R, Clayton D, McKeigue P . Design and analysis of admixture mapping studies. Am J Hum Genet. 2004; 74(5):965-78. PMC: 1181989. DOI: 10.1086/420855. View

Lovell A, Moreau C, Yotova V, Xiao F, Bourgeois S, Gehl D . Ethiopia: between Sub-Saharan Africa and western Eurasia. Ann Hum Genet. 2005; 69(Pt 3):275-87. DOI: 10.1046/j.1529-8817.2005.00152.x. View

. A haplotype map of the human genome. Nature. 2005; 437(7063):1299-320. PMC: 1880871. DOI: 10.1038/nature04226. View

Schaffner S, Foo C, Gabriel S, Reich D, Daly M, Altshuler D . Calibrating a coalescent simulation of human genome sequence variation. Genome Res. 2005; 15(11):1576-83. PMC: 1310645. DOI: 10.1101/gr.3709305. View

Daly M, Rioux J, Schaffner S, Hudson T, Lander E . High-resolution haplotype structure in the human genome. Nat Genet. 2001; 29(2):229-32. DOI: 10.1038/ng1001-229. View

Allen A, Rathouz P, Satten G . Informative missingness in genetic association studies: case-parent designs. Am J Hum Genet. 2003; 72(3):671-80. PMC: 1180242. DOI: 10.1086/368276. View

10.

Price A, Patterson N, Plenge R, Weinblatt M, Shadick N, Reich D . Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006; 38(8):904-9. DOI: 10.1038/ng1847. View

11.

Clayton D, Walker N, Smyth D, Pask R, Cooper J, Maier L . Population structure, differential bias and genomic control in a large-scale, case-control association study. Nat Genet. 2005; 37(11):1243-6. DOI: 10.1038/ng1653. View

12.

Montana G, Pritchard J . Statistical tests for admixture mapping with case-control and cases-only data. Am J Hum Genet. 2004; 75(5):771-89. PMC: 1182107. DOI: 10.1086/425281. View

13.

Menozzi P, Piazza A, CAVALLI-SFORZA L . Synthetic maps of human gene frequencies in Europeans. Science. 1978; 201(4358):786-92. DOI: 10.1126/science.356262. View

14.

Capelli C, Redhead N, Romano V, Cali F, Lefranc G, Delague V . Population structure in the Mediterranean basin: a Y chromosome perspective. Ann Hum Genet. 2006; 70(Pt 2):207-25. DOI: 10.1111/j.1529-8817.2005.00224.x. View

15.

Shriver M, Mei R, Parra E, Sonpar V, Halder I, Tishkoff S . Large-scale SNP analysis reveals clustered and continuous patterns of human genetic variation. Hum Genomics. 2005; 2(2):81-9. PMC: 3525270. DOI: 10.1186/1479-7364-2-2-81. View

16.

Freedman M, Reich D, Penney K, McDonald G, Mignault A, Patterson N . Assessing the impact of population stratification on genetic association studies. Nat Genet. 2004; 36(4):388-93. DOI: 10.1038/ng1333. View

17.

Bowcock A, Ruiz-Linares A, Tomfohrde J, Minch E, Kidd J, Cavalli-Sforza L . High resolution of human evolutionary trees with polymorphic microsatellites. Nature. 1994; 368(6470):455-7. DOI: 10.1038/368455a0. View

18.

Patil N, Berno A, Hinds D, BARRETT W, Doshi J, Hacker C . Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21. Science. 2001; 294(5547):1719-23. DOI: 10.1126/science.1065573. View

19.

Devlin B, Roeder K . Genomic control for association studies. Biometrics. 2001; 55(4):997-1004. DOI: 10.1111/j.0006-341x.1999.00997.x. View

20.

Chakraborty R, Jin L . A unified approach to study hypervariable polymorphisms: statistical considerations of determining relatedness and population distances. EXS. 1993; 67:153-75. DOI: 10.1007/978-3-0348-8583-6_14. View