Investigation of the fine structure of European populations with applications to disease association studies.
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.
Heath
Simon C
SC
Centre National de Genotypage, Institut Genomique, Commissariat à l'énergie Atomique, Evry, France. simon.heath@gmail.com
Gut
Ivo G
IG
Brennan
Paul
P
McKay
James D
JD
Bencko
Vladimir
V
Fabianova
Eleonora
E
Foretova
Lenka
L
Georges
Michael
M
Janout
Vladimir
V
Kabesch
Michael
M
Krokan
Hans E
HE
Elvestad
Maiken B
MB
Lissowska
Jolanta
J
Mates
Dana
D
Rudnai
Peter
P
Skorpen
Frank
F
Schreiber
Stefan
S
Soria
José M
JM
Syvänen
Ann-Christine
AC
Meneton
Pierre
P
Herçberg
Serge
S
Galan
Pilar
P
Szeszenia-Dabrowska
Neonilia
N
Zaridze
David
D
Génin
Emmanuel
E
Cardon
Lon R
LR
Lathrop
Mark
M
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