title: Discerning the ancestry of European Americans in genetic association studies.
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.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America. aprice@broad.mit.edu
authors.forename: Alkes L
authors.initials: AL
authors.lastname: Price
authors.forename: Johannah
authors.initials: J
authors.lastname: Butler
authors.forename: Nick
authors.initials: N
authors.lastname: Patterson
authors.forename: Cristian
authors.initials: C
authors.lastname: Capelli
authors.forename: Vincenzo L
authors.initials: VL
authors.lastname: Pascali
authors.forename: Francesca
authors.initials: F
authors.lastname: Scarnicci
authors.forename: Andres
authors.initials: A
authors.lastname: Ruiz-Linares
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Angelica A
authors.initials: AA
authors.lastname: Saetta
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.forename: Uri
authors.initials: U
authors.lastname: Seligsohn
authors.forename: Alicja
authors.initials: A
authors.lastname: Waliszewska
authors.forename: Christine
authors.initials: C
authors.lastname: Schirmer
authors.forename: Kristin
authors.initials: K
authors.lastname: Ardlie
authors.forename: Alexis
authors.initials: A
authors.lastname: Ramos
authors.forename: James
authors.initials: J
authors.lastname: Nemesh
authors.forename: Lori
authors.initials: L
authors.lastname: Arbeitman
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
authors.forename: David
authors.initials: D
authors.lastname: Reich
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D005819:Genetic Markers; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human; D005843:Geography; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D007585:Jews / Q000208:ethnology; D009103:Multiple Sclerosis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010300:Parkinson Disease / Q000235:genetics; D015203:Reproducibility of Results; D014481:United States; D044465:White People / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D004247:DNA