title: Investigation of the fine structure of European populations with applications to disease association studies.
abstract: An investigation into fine-scale European population structure was carried out using high-density genetic variation on nearly 6000 individuals originating from across Europe. The individuals were collected as control samples and were genotyped with more than 300 000 SNPs in genome-wide association studies using the Illumina Infinium platform. A major East-West gradient from Russian (Moscow) samples to Spanish samples was identified as the first principal component (PC) of the genetic diversity. The second PC identified a North-South gradient from Norway and Sweden to Romania and Spain. Variation of frequencies at markers in three separate genomic regions, surrounding LCT, HLA and HERC2, were strongly associated with this gradient. The next 18 PCs also accounted for a significant proportion of genetic diversity observed in the sample. We present a method to predict the ethnic origin of samples by comparing the sample genotypes with those from a reference set of samples of known origin. These predictions can be performed using just summary information on the known samples, and individual genotype data are not required. We discuss issues raised by these data and analyses for association studies including the matching of case-only cohorts to appropriate pre-collected control samples for genome-wide association studies.
authors.affiliation: Centre National de Genotypage, Institut Genomique, Commissariat à l'énergie Atomique, Evry, France. simon.heath@gmail.com
authors.forename: Simon C
authors.initials: SC
authors.lastname: Heath
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Gut
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: James D
authors.initials: JD
authors.lastname: McKay
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bencko
authors.forename: Eleonora
authors.initials: E
authors.lastname: Fabianova
authors.forename: Lenka
authors.initials: L
authors.lastname: Foretova
authors.forename: Michael
authors.initials: M
authors.lastname: Georges
authors.forename: Vladimir
authors.initials: V
authors.lastname: Janout
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
authors.forename: Hans E
authors.initials: HE
authors.lastname: Krokan
authors.forename: Maiken B
authors.initials: MB
authors.lastname: Elvestad
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Dana
authors.initials: D
authors.lastname: Mates
authors.forename: Peter
authors.initials: P
authors.lastname: Rudnai
authors.forename: Frank
authors.initials: F
authors.lastname: Skorpen
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: José M
authors.initials: JM
authors.lastname: Soria
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Syvänen
authors.forename: Pierre
authors.initials: P
authors.lastname: Meneton
authors.forename: Serge
authors.initials: S
authors.lastname: Herçberg
authors.forename: Pilar
authors.initials: P
authors.lastname: Galan
authors.forename: Neonilia
authors.initials: N
authors.lastname: Szeszenia-Dabrowska
authors.forename: David
authors.initials: D
authors.lastname: Zaridze
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Génin
authors.forename: Lon R
authors.initials: LR
authors.lastname: Cardon
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D004194:Disease / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005828:Genetics, Population / Q000379:methods*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide