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Discerning the ancestry of European Americans in genetic association studies

Price, AL; Butler, J; Patterson, N; Capelli, C; Pascali, VL; Scarnicci, F; Ruiz-Linares, A; ... Hirschhorn, JN; + view all (2008) Discerning the ancestry of European Americans in genetic association studies. PLOS GENET , 4 (1) , Article e236. 10.1371/journal.pgen.0030236. Green open access

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Abstract

European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false-positive or false-negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data.

Type: Article
Title: Discerning the ancestry of European Americans in genetic association studies
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pgen.0030236
Publisher version: http://dx.doi.org/10.1371/journal.pgen.0030236
Language: English
Additional information: © 2008 Price et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: ALP is supported by a Ruth Kirschstein K-08 award from the National Institutes of Health, DR and JNH are both recipients of Burroughs Wellcome Career Development Awards in the Biomedical Sciences, and JNH is supported by a March of Dimes research grant and the American Diabetes Association Smith Family Foundation Pinnacle Program Project. DR, ALP and NP were also supported by NIH grant U01 HG004168. The Broad Institute Center for Genotyping and Analysis is supported by National Center for Research Resources grant U54 RR020278.
Keywords: GENOME-WIDE ASSOCIATION, INFLAMMATORY-BOWEL-DISEASE, POPULATION STRATIFICATION, RISK, PIGMENTATION, POLYMORPHISM, FREQUENCIES, GENOTYPE, NORTHERN, JEWS
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/1319054
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