Genetic differences between five European populations.
OBJECTIVE
We sought to examine the magnitude of the differences in SNP allele frequencies between five European populations (Scotland, Ireland, Sweden, Bulgaria and Portugal) and to identify the loci with the greatest differences.


METHODS
We performed a population-based genome-wide association analysis with Affymetrix 6.0 and 5.0 arrays. We used a 4 degrees of freedom χ(2) test to determine the magnitude of stratification for each SNP. We then examined the genes within the most stratified regions, using a highly conservative cutoff of p < 10(-45).


RESULTS
We found 40,593 SNPs which are genome-wide significantly (p ≤ 10(-8)) stratified between these populations. The largest differences clustered in gene ontology categories for immunity and pigmentation. Some of the top loci span genes that have already been reported as highly stratified: genes for hair color and pigmentation (HERC2, EXOC2, IRF4), the LCT gene, genes involved in NAD metabolism, and in immunity (HLA and the Toll-like receptor genes TLR10, TLR1, TLR6). However, several genes have not previously been reported as stratified within European populations, indicating that they might also have provided selective advantages: several zinc finger genes, two genes involved in glutathione synthesis or function, and most intriguingly, FOXP2, implicated in speech development.


CONCLUSIONS
Our analysis demonstrates that many SNPs show genome-wide significant differences within European populations and the magnitude of the differences correlate with the geographical distance. At least some of these differences are due to the selective advantage of polymorphisms within these loci.
Moskvina
Valentina
V
MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK.
Smith
Michael
M
Ivanov
Dobril
D
Blackwood
Douglas
D
StClair
David
D
Hultman
Christina
C
Toncheva
Draga
D
Gill
Michael
M
Corvin
Aiden
A
O'Dushlaine
Colm
C
Morris
Derek W
DW
Wray
Naomi R
NR
Sullivan
Patrick
P
Pato
Carlos
C
Pato
Michele T
MT
Sklar
Pamela
P
Purcell
Shaun
S
Holmans
Peter
P
O'Donovan
Michael C
MC
Owen
Michael J
MJ
Kirov
George
G
D005828:Genetics, Population; D006801:Humans; D043322:Lactase / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics*
D043322:Lactase