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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, Groop L, Saetta AA, Korkolopoulou P, Seligsohn U, Waliszewska A, Schirmer C, Ardlie K, Ramos A, Nemesh J, Arbeitman L, Goldstein DB, Reich D, Hirschhorn JN - PLoS Genet. (2007)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America. aprice@broad.mit.edu

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.

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The Top Two Axes of Variation of the Combined Dataset (MS, BD, PD, and IBD)Samples from the IBD dataset are labeled according to self-reported ancestry, as in Figure 1E.
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pgen-0030236-g002: The Top Two Axes of Variation of the Combined Dataset (MS, BD, PD, and IBD)Samples from the IBD dataset are labeled according to self-reported ancestry, as in Figure 1E.

Mentions: To determine whether the visually similar patterns observed in these four datasets each represent the same underlying components of ancestry, we constructed a combined dataset of MS, BD, PD and IBD samples using markers present in all datasets. The top two principal components of the combined dataset, displayed in Figure 2, are similar to the plots in Figure 1 and show the same rough correspondence to self-reported ancestry labels from the IBD study.


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, Groop L, Saetta AA, Korkolopoulou P, Seligsohn U, Waliszewska A, Schirmer C, Ardlie K, Ramos A, Nemesh J, Arbeitman L, Goldstein DB, Reich D, Hirschhorn JN - PLoS Genet. (2007)

The Top Two Axes of Variation of the Combined Dataset (MS, BD, PD, and IBD)Samples from the IBD dataset are labeled according to self-reported ancestry, as in Figure 1E.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211542&req=5

pgen-0030236-g002: The Top Two Axes of Variation of the Combined Dataset (MS, BD, PD, and IBD)Samples from the IBD dataset are labeled according to self-reported ancestry, as in Figure 1E.
Mentions: To determine whether the visually similar patterns observed in these four datasets each represent the same underlying components of ancestry, we constructed a combined dataset of MS, BD, PD and IBD samples using markers present in all datasets. The top two principal components of the combined dataset, displayed in Figure 2, are similar to the plots in Figure 1 and show the same rough correspondence to self-reported ancestry labels from the IBD study.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America. aprice@broad.mit.edu

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.

Show MeSH