Geographical structure and differential natural selection among North European populations

Brian P. McEvoy; Grant W. Montgomery; Allan F. McRae; Samuli Ripatti; Markus Perola; Tim D. Spector; Lynn Cherkas; Kourosh R. Ahmadi; Dorret Boomsma; Gonneke Willemsen; Jouke J. Hottenga; Nancy L. Pedersen; Patrik K. E. Magnusson; Kirsten Ohm Kyvik; Kaare Christensen; Jaakko Kaprio; Kauko Heikkila; Aarno Palotie; Elisabeth Widen; Juha Muilu; Ann-Christine Syvanen; Ulrika Liljedahl; Orla Hardiman; Simon Cronin; Leena Peltonen; Nicholas G. Martin; Peter M. Visscher

doi:10.1101/gr.083394.108

Geographical structure and differential natural selection among North European populations

Brian P. McEvoy, Grant W. Montgomery, Allan F. McRae, Samuli Ripatti, Markus Perola, Tim D. Spector, Lynn Cherkas, Kourosh R. Ahmadi, Dorret Boomsma, Gonneke Willemsen, Jouke J. Hottenga, Nancy L. Pedersen, Patrik K. E. Magnusson, Kirsten Ohm Kyvik, Kaare Christensen, Jaakko Kaprio, Kauko Heikkila, Aarno Palotie, Elisabeth Widen, Juha MuiluAnn-Christine Syvanen, Ulrika Liljedahl, Orla Hardiman, Simon Cronin, Leena Peltonen, Nicholas G. Martin, Peter M. Visscher

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Abstract

Population structure can provide novel insight into the human past, and recognizing and correcting for such stratification is a practical concern in gene mapping by many association methodologies. We investigate these patterns, primarily through principal component (PC) analysis of whole genome SNP polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like the British Isles, and this information can then be applied to finely dissect the ancestry of the European-Australian and European-American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogeneous region. There is evidence from FST-based analysis of genic and nongenic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic. Such an event may explain a striking selective sweep centered on the rs2508049-G allele, close to the HLA-G gene on chromosome 6. Evidence of the sweep extends over a 8-Mb/3.5-cM region. Overall, the results illustrate the power of dense genotype and sample data to explore regional population variation, the events that have crafted it, and their implications in both explaining disease prevalence and mapping these genes by association.

Original language	English
Pages (from-to)	804 - 814
Number of pages	11
Journal	Genome Research
Volume	19
Issue number	5
DOIs	https://doi.org/10.1101/gr.083394.108
Publication status	Published - May 2009

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McEvoy, B. P., Montgomery, G. W., McRae, A. F., Ripatti, S., Perola, M., Spector, T. D., Cherkas, L., Ahmadi, K. R., Boomsma, D., Willemsen, G., Hottenga, J. J., Pedersen, N. L., Magnusson, P. K. E., Kyvik, K. O., Christensen, K., Kaprio, J., Heikkila, K., Palotie, A., Widen, E., ... Visscher, P. M. (2009). Geographical structure and differential natural selection among North European populations. Genome Research, 19(5), 804 - 814. https://doi.org/10.1101/gr.083394.108

@article{a0cfe2e5e8d74d2584dbd3d547c6318a,

title = "Geographical structure and differential natural selection among North European populations",

abstract = "Population structure can provide novel insight into the human past, and recognizing and correcting for such stratification is a practical concern in gene mapping by many association methodologies. We investigate these patterns, primarily through principal component (PC) analysis of whole genome SNP polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like the British Isles, and this information can then be applied to finely dissect the ancestry of the European-Australian and European-American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogeneous region. There is evidence from FST-based analysis of genic and nongenic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic. Such an event may explain a striking selective sweep centered on the rs2508049-G allele, close to the HLA-G gene on chromosome 6. Evidence of the sweep extends over a 8-Mb/3.5-cM region. Overall, the results illustrate the power of dense genotype and sample data to explore regional population variation, the events that have crafted it, and their implications in both explaining disease prevalence and mapping these genes by association.",

author = "McEvoy, {Brian P.} and Montgomery, {Grant W.} and McRae, {Allan F.} and Samuli Ripatti and Markus Perola and Spector, {Tim D.} and Lynn Cherkas and Ahmadi, {Kourosh R.} and Dorret Boomsma and Gonneke Willemsen and Hottenga, {Jouke J.} and Pedersen, {Nancy L.} and Magnusson, {Patrik K. E.} and Kyvik, {Kirsten Ohm} and Kaare Christensen and Jaakko Kaprio and Kauko Heikkila and Aarno Palotie and Elisabeth Widen and Juha Muilu and Ann-Christine Syvanen and Ulrika Liljedahl and Orla Hardiman and Simon Cronin and Leena Peltonen and Martin, {Nicholas G.} and Visscher, {Peter M.}",

year = "2009",

month = may,

doi = "10.1101/gr.083394.108",

language = "English",

volume = "19",

pages = "804 -- 814",

journal = "Genome Research",

publisher = "Cold Spring Harbor Laboratory Press",

number = "5",

}

McEvoy, BP, Montgomery, GW, McRae, AF, Ripatti, S, Perola, M, Spector, TD , Cherkas, L , Ahmadi, KR, Boomsma, D, Willemsen, G, Hottenga, JJ, Pedersen, NL, Magnusson, PKE, Kyvik, KO, Christensen, K, Kaprio, J, Heikkila, K, Palotie, A, Widen, E, Muilu, J, Syvanen, A-C, Liljedahl, U, Hardiman, O, Cronin, S, Peltonen, L, Martin, NG & Visscher, PM 2009, 'Geographical structure and differential natural selection among North European populations', Genome Research, vol. 19, no. 5, pp. 804 - 814. https://doi.org/10.1101/gr.083394.108

TY - JOUR

T1 - Geographical structure and differential natural selection among North European populations

AU - McEvoy, Brian P.

AU - Montgomery, Grant W.

AU - McRae, Allan F.

AU - Ripatti, Samuli

AU - Perola, Markus

AU - Spector, Tim D.

AU - Cherkas, Lynn

AU - Ahmadi, Kourosh R.

AU - Boomsma, Dorret

AU - Willemsen, Gonneke

AU - Hottenga, Jouke J.

AU - Pedersen, Nancy L.

AU - Magnusson, Patrik K. E.

AU - Kyvik, Kirsten Ohm

AU - Christensen, Kaare

AU - Kaprio, Jaakko

AU - Heikkila, Kauko

AU - Palotie, Aarno

AU - Widen, Elisabeth

AU - Muilu, Juha

AU - Syvanen, Ann-Christine

AU - Liljedahl, Ulrika

AU - Hardiman, Orla

AU - Cronin, Simon

AU - Peltonen, Leena

AU - Martin, Nicholas G.

AU - Visscher, Peter M.

PY - 2009/5

Y1 - 2009/5

N2 - Population structure can provide novel insight into the human past, and recognizing and correcting for such stratification is a practical concern in gene mapping by many association methodologies. We investigate these patterns, primarily through principal component (PC) analysis of whole genome SNP polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like the British Isles, and this information can then be applied to finely dissect the ancestry of the European-Australian and European-American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogeneous region. There is evidence from FST-based analysis of genic and nongenic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic. Such an event may explain a striking selective sweep centered on the rs2508049-G allele, close to the HLA-G gene on chromosome 6. Evidence of the sweep extends over a 8-Mb/3.5-cM region. Overall, the results illustrate the power of dense genotype and sample data to explore regional population variation, the events that have crafted it, and their implications in both explaining disease prevalence and mapping these genes by association.

AB - Population structure can provide novel insight into the human past, and recognizing and correcting for such stratification is a practical concern in gene mapping by many association methodologies. We investigate these patterns, primarily through principal component (PC) analysis of whole genome SNP polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like the British Isles, and this information can then be applied to finely dissect the ancestry of the European-Australian and European-American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogeneous region. There is evidence from FST-based analysis of genic and nongenic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic. Such an event may explain a striking selective sweep centered on the rs2508049-G allele, close to the HLA-G gene on chromosome 6. Evidence of the sweep extends over a 8-Mb/3.5-cM region. Overall, the results illustrate the power of dense genotype and sample data to explore regional population variation, the events that have crafted it, and their implications in both explaining disease prevalence and mapping these genes by association.

U2 - 10.1101/gr.083394.108

DO - 10.1101/gr.083394.108

M3 - Article

VL - 19

SP - 804

EP - 814

JO - Genome Research

JF - Genome Research

IS - 5

ER -

Geographical structure and differential natural selection among North European populations

Abstract

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