title: Inferring geographic coordinates of origin for Europeans using small panels of ancestry informative markers.
abstract: Recent large-scale studies of European populations have demonstrated the existence of population genetic structure within Europe and the potential to accurately infer individual ancestry when information from hundreds of thousands of genetic markers is used. In fact, when genomewide genetic variation of European populations is projected down to a two-dimensional Principal Components Analysis plot, a surprising correlation with actual geographic coordinates of self-reported ancestry has been reported. This substructure can hamper the search of susceptibility genes for common complex disorders leading to spurious correlations. The identification of genetic markers that can correct for population stratification becomes therefore of paramount importance. Analyzing 1,200 individuals from 11 populations genotyped for more than 500,000 SNPs (Population Reference Sample), we present a systematic exploration of the extent to which geographic coordinates of origin within Europe can be predicted, with small panels of SNPs. Markers are selected to correlate with the top principal components of the dataset, as we have previously demonstrated. Performing thorough cross-validation experiments we show that it is indeed possible to predict individual ancestry within Europe down to a few hundred kilometers from actual individual origin, using information from carefully selected panels of 500 or 1,000 SNPs. Furthermore, we show that these panels can be used to correctly assign the HapMap Phase 3 European populations to their geographic origin. The SNPs that we propose can prove extremely useful in a variety of different settings, such as stratification correction or genetic ancestry testing, and the study of the history of European populations.
authors.affiliation: Department of Computer Science, Rensselaer Polytechnic Institute, Troy, New York, United States of America.
authors.forename: Petros
authors.initials: P
authors.lastname: Drineas
authors.forename: Jamey
authors.initials: J
authors.lastname: Lewis
authors.forename: Peristera
authors.initials: P
authors.lastname: Paschou
mesh_terms: D000465:Algorithms; D016208:Databases, Factual; D005060:Europe; D005819:Genetic Markers / Q000235:genetics*; D005843:Geography; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D025341:Principal Component Analysis; D015203:Reproducibility of Results; D044465:White People / Q000235:genetics*
chemical_list: D005819:Genetic Markers
references.citation: Am J Hum Genet. 1994 Oct;55(4):788-808
references.pmid: 7942857
references.citation: Am J Hum Genet. 2002 Mar;70(3):737-50
references.pmid: 11845411
references.citation: Am J Hum Genet. 1998 Jul;63(1):241-51
references.pmid: 9634509
references.citation: PLoS Genet. 2008 Jan;4(1):e236
references.pmid: 18208327
references.citation: Am J Hum Genet. 2003 Dec;73(6):1402-22
references.pmid: 14631557
references.citation: Ann Eugen. 1951 Mar;15(4):323-54
references.pmid: 24540312
references.citation: Mol Med. 2009 Nov-Dec;15(11-12):371-83
references.pmid: 19707526
references.citation: Genome Res. 2009 May;19(5):804-14
references.pmid: 19265028
references.citation: Eur J Hum Genet. 2008 Dec;16(12):1413-29
references.pmid: 19020537
references.citation: Science. 2008 Feb 22;319(5866):1100-4
references.pmid: 18292342
references.citation: PLoS Genet. 2006 Sep 15;2(9):e143
references.pmid: 17044734
references.citation: Nat Genet. 2005 Aug;37(8):868-72
references.pmid: 16041375
references.citation: Nature. 2007 Oct 18;449(7164):913-8
references.pmid: 17943131
references.citation: PLoS Genet. 2008 Jul 04;4(7):e1000114
references.pmid: 18797516
references.citation: Nature. 2008 Nov 6;456(7218):98-101
references.pmid: 18758442
references.citation: Am J Hum Genet. 1998 Dec;63(6):1839-51
references.pmid: 9837836
references.citation: Curr Biol. 2008 Aug 26;18(16):1241-8
references.pmid: 18691889
references.citation: Proc Biol Sci. 2006 Jul 7;273(1594):1595-602
references.pmid: 16769629
references.citation: Am J Hum Genet. 2008 Sep;83(3):347-58
references.pmid: 18760391
references.citation: Am J Hum Genet. 2009 May;84(5):641-50
references.pmid: 19442770
references.citation: Am J Hum Genet. 2001 Oct;69(4):844-52
references.pmid: 11517423
references.citation: N Engl J Med. 2002 Sep 19;347(12):911-20
references.pmid: 12239261
references.citation: PLoS Genet. 2007 Sep;3(9):1672-86
references.pmid: 17892327
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11008-13
references.pmid: 12167671
references.citation: PLoS Genet. 2008 Jan;4(1):e4
references.pmid: 18208329
references.citation: Nat Genet. 2004 May;36(5):512-7
references.pmid: 15052271
references.citation: Am J Hum Genet. 2007 May;80(5):948-56
references.pmid: 17436249