Abstract
Analyzing genetic variation of human populations for detecting loci that have been affected by positive natural selection is important for understanding adaptive history and phenotypic variation in humans. In this study, we analyzed recent positive selection in Northern Europe from genome-wide data sets of 250 000 and 500 000 single-nucleotide polymorphisms (SNPs) in a total of 999 individuals from Great Britain, Northern Germany, Eastern and Western Finland, and Sweden. Coalescent simulations were used for demonstrating that the integrated haplotype score (iHS) and long-range haplotype (LRH) statistics have sufficient power in genome-wide data sets of different sample sizes and SNP densities. Furthermore, the behavior of the FST statistic in closely related populations was characterized by allele frequency simulations. In the analysis of the North European data set, 60 regions in the genome showed strong signs of recent positive selection. Out of these, 21 regions have not been discovered in previous scans, and many contain genes with interesting functions (eg, RAB38, INFG, NOS1AP, and APOE). In the putatively selected regions, we observed a statistically significant overrepresentation of genetic association with complex disease, which emphasizes the importance of the analysis of positive selection in understanding the evolution of human disease. Altogether, this study demonstrates the potential of genome-wide data sets to discover loci that lie behind evolutionary adaptation in different human populations.
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Acknowledgements
The funding for this study has been provided by the Emil Aaltonen foundation, the Research Foundation of the University of Helsinki, the Graduate School in Computational Biology, Bioinformatics, and Biometry, the Sigrid Juselius Foundation, the Academy of Finland, the Swedish Research Council, the Finnish Cultural Foundation, the National Genome Research Network (NGFN), and the PopGen Biobank, both through the German Ministry of Education and Science, and DFG excellence cluster ‘inflammation at interfaces’. Funding for the WTCCC project was provided by the Wellcome Trust under Award 076113. This study makes use of the data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Furthermore, we thank Ingegerd Fransson and the personnel at Bioinformatics and Expression analysis core facility at Karolinska Institutet for technical support.
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Lappalainen, T., Salmela, E., Andersen, P. et al. Genomic landscape of positive natural selection in Northern European populations. Eur J Hum Genet 18, 471–478 (2010). https://doi.org/10.1038/ejhg.2009.184
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DOI: https://doi.org/10.1038/ejhg.2009.184
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