Genetic structure of Europeans: a view from the North-East.
Using principal component (PC) analysis, we studied the genetic constitution of 3,112 individuals from Europe as portrayed by more than 270,000 single nucleotide polymorphisms (SNPs) genotyped with the Illumina Infinium platform. In cohorts where the sample size was >100, one hundred randomly chosen samples were used for analysis to minimize the sample size effect, resulting in a total of 1,564 samples. This analysis revealed that the genetic structure of the European population correlates closely with geography. The first two PCs highlight the genetic diversity corresponding to the northwest to southeast gradient and position the populations according to their approximate geographic origin. The resulting genetic map forms a triangular structure with a) Finland, b) the Baltic region, Poland and Western Russia, and c) Italy as its vertexes, and with d) Central- and Western Europe in its centre. Inter- and intra- population genetic differences were quantified by the inflation factor lambda (lambda) (ranging from 1.00 to 4.21), fixation index (F(st)) (ranging from 0.000 to 0.023), and by the number of markers exhibiting significant allele frequency differences in pair-wise population comparisons. The estimated lambda was used to assess the real diminishing impact to association statistics when two distinct populations are merged directly in an analysis. When the PC analysis was confined to the 1,019 Estonian individuals (0.1% of the Estonian population), a fine structure emerged that correlated with the geography of individual counties. With at least two cohorts available from several countries, genetic substructures were investigated in Czech, Finnish, German, Estonian and Italian populations. Together with previously published data, our results allow the creation of a comprehensive European genetic map that will greatly facilitate inter-population genetic studies including genome wide association studies (GWAS).
Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Mari
M
Nelis
Tõnu
T
Esko
Reedik
R
Mägi
Fritz
F
Zimprich
Alexander
A
Zimprich
Draga
D
Toncheva
Sena
S
Karachanak
Tereza
T
Piskácková
Ivan
I
Balascák
Leena
L
Peltonen
Eveliina
E
Jakkula
Karola
K
Rehnström
Mark
M
Lathrop
Simon
S
Heath
Pilar
P
Galan
Stefan
S
Schreiber
Thomas
T
Meitinger
Arne
A
Pfeufer
H-Erich
HE
Wichmann
Béla
B
Melegh
Noémi
N
Polgár
Daniela
D
Toniolo
Paolo
P
Gasparini
Pio
P
D'Adamo
Janis
J
Klovins
Liene
L
Nikitina-Zake
Vaidutis
V
Kucinskas
Jūrate
J
Kasnauskiene
Jan
J
Lubinski
Tadeusz
T
Debniak
Svetlana
S
Limborska
Andrey
A
Khrunin
Xavier
X
Estivill
Raquel
R
Rabionet
Sara
S
Marsal
Antonio
A
Julià
Stylianos E
SE
Antonarakis
Samuel
S
Deutsch
Christelle
C
Borel
Homa
H
Attar
Maryline
M
Gagnebin
Milan
M
Macek
Michael
M
Krawczak
Maido
M
Remm
Andres
A
Metspalu
D005060:Europe / Q000208:ethnology; D005787:Gene Frequency; D005819:Genetic Markers; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D044465:White People / Q000235:genetics*
D005819:Genetic Markers