TY - JOUR A1 - McEvoy, Brian P A1 - Montgomery, Grant W A1 - McRae, Allan F A1 - Ripatti, Samuli A1 - Perola, Markus A1 - Spector, Tim D A1 - Cherkas, Lynn A1 - Ahmadi, Kourosh R A1 - Boomsma, Dorret A1 - Willemsen, Gonneke A1 - Hottenga, Jouke Jan A1 - Peterson, Nancy L A1 - Magnusson, Patrik KE A1 - Ohm Kyvik, Kirsten A1 - Christensen, Kaare A1 - Kaprio, Jaako A1 - Heikkila, Kauko A1 - Palotie, Aarno A1 - Widen, Elisabeth A1 - Muilu, Juha A1 - Syvanen, Anne-Christine A1 - Liljedahl, Ulrika A1 - Hardiman, Orla A1 - Cronin, Simon A1 - Peltonen, Leena A1 - Martin, Nicholas G A1 - Visscher, Peter M T1 - Geographical structure and differential natural selection amongst North European populations Y1 - 2009/01/01 JF - Genome Research JO - Genome Research DO - 10.1101/gr.083394.108 SP - gr.083394.108 UR - http://genome.cshlp.org/content/early/2009/03/05/gr.083394.108.abstract 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, UK, 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 -American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogenous region. There is evidence from FST based analysis of genic and non-genic 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 HLA-G gene on chromosome 6. Evidence of the sweep extends over 8Mb/3.5cM 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 ER -