TY - JOUR T1 - Discerning the Ancestry of European Americans in Genetic Association Studies A1 - Price, Alkes L A1 - Butler, Johannah A1 - Patterson, Nick A1 - Capelli, Cristian A1 - Pascali, Vincenzo L A1 - Scarnicci, Francesca A1 - Ruiz-Linares, Andres A1 - Groop, Leif A1 - Saetta, Angelica A A1 - Korkolopoulou, Penelope A1 - Seligsohn, Uri A1 - Waliszewska, Alicja A1 - Schirmer, Christine A1 - Ardlie, Kristin A1 - Ramos, Alexis A1 - Nemesh, James A1 - Arbeitman, Lori A1 - Goldstein, David B A1 - Reich, David A1 - Hirschhorn, Joel N Y1 - 2008/01/18 N2 -
Genetic association studies analyze both phenotypes (such as disease status) and genotypes (at sites of DNA variation) of a given set of individuals. The goal of association studies is to identify DNA variants that affect disease risk or other traits of interest. However, association studies can be confounded by differences in ancestry. For example, misleading results can arise if individuals selected as disease cases have different ancestry, on average, than healthy controls. Although geographic ancestry explains only a small fraction of human genetic variation, there exist genetic variants that are much more frequent in populations with particular ancestries, and such variants would falsely appear to be related to disease. In an effort to avoid these spurious results, association studies often restrict their focus to a single continental group. European Americans are one such group that is commonly studied in the United States. Here, we analyze multiple large European American datasets to show that important differences in ancestry exist even within European Americans, and that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the major, consistent sources of variation. We provide an approach that is able to account for these ancestry differences in association studies even if only a small number of genes is studied.