Genetic Differences between Five European Populations (original) (raw)
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Research Articles| July 08 2010
aMRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff,
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aMRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff,
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aMRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff,
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bDivision of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, and
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cInstitute of Medical Sciences, University of Aberdeen, Aberdeen, UK;
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dDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;
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eDepartment of Medical Genetics, University Hospital Maichin Dom, Sofia, Bulgaria;
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fNeuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland;
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fNeuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland;
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fNeuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland;
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fNeuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland;
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gQueensland Institute of Medical Research, Brisbane, Qld., Australia;
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hDepartment of Genetics, University of North Carolina, Chapel Hill, N.C.,
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iDepartment of Psychiatry and the Behavioral Sciences, Franz Alexander Chair in Psychiatry, Keck School of Medicine at USC, Los Angeles, Calif.,
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iDepartment of Psychiatry and the Behavioral Sciences, Franz Alexander Chair in Psychiatry, Keck School of Medicine at USC, Los Angeles, Calif.,
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jBroad Institute of Harvard and MIT, Cambridge, Mass., and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Mass., USA
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jBroad Institute of Harvard and MIT, Cambridge, Mass., and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Mass., USA
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aMRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff,
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aMRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff,
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aMRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff,
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aMRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff,
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Hum Hered (2010) 70 (2): 141–149.
Citation
Valentina Moskvina, Michael Smith, Dobril Ivanov, Douglas Blackwood, David StClair, Christina Hultman, Draga Toncheva, Michael Gill, Aiden Corvin, Colm O’Dushlaine, Derek W. Morris, Naomi R. Wray, Patrick Sullivan, Carlos Pato, Michele T. Pato, Pamela Sklar, Shaun Purcell, Peter Holmans, Michael C. O’Donovan, Michael J. Owen, George Kirov, International Schizophrenia Consortium; Genetic Differences between Five European Populations. _Hum Hered 1 July 2010; 70 (2): 141–149. https://doi.org/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.
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2010
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