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Genetic differences between five European populations

Escott-Price, Valentina, Smith, Michael, Ivanov, Dobril, Blackwood, Douglas, StClair, David, Hultman, Christina, Toncheva, Draga, Gill, Michael, Corvin, Aiden, O'Dushlaine, Colm, Morris, Derek W., Wray, Naomi R., Sullivan, Patrick, Pato, Carlos, Pato, Michele T., Sklar, Pamela, Purcell, Shaun, Holmans, Peter Alan, O'Donovan, Michael Conolon, Owen, Michael John and Kirov, George 2010. Genetic differences between five European populations. Human Heredity 70 (2) , pp. 141-149. 10.1159/000313854

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Abstract

Aims: 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 χ2 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. Conclusion: 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Systems Immunity Research Institute (SIURI)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Uncontrolled Keywords: Population; gene; stratification; pigmentation; immunity
Publisher: Karger
ISSN: 1423-0062
Date of Acceptance: 17 April 2010
Last Modified: 02 May 2019 12:34
URI: http://orca.cf.ac.uk/id/eprint/27654

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