accounting for population stratification in practice a comparison of the main strategies dedicated to genome-wide association studies占人口分层在实践中比较致力于全基因组关联研究的主要策略.pdfVIP

Accounting for Population Stratification in Practice: A Comparison of the Main Strategies Dedicated to Genome-Wide Association Studies 1,2 2 1 Matthieu Bouaziz *, Christophe Ambroise , Mickael Guedj 1 Department of Biostatistics, Pharnext, Paris, France, 2 Statistics and Genome Laboratory, University of Evry Val d’Essonne, UMR CNRS 8071 - USC INRA, Evry, France Abstract Genome-Wide Association Studies are powerful tools to detect genetic variants associated with diseases. Their results have, however, been questioned, in part because of the bias induced by population stratification. This is a consequence of systematic differences in allele frequencies due to the difference in sample ancestries that can lead to both false positive or false negative findings. Many strategies are available to account for stratification but their performances differ, for instance according to the type of population structure, the disease susceptibility locus minor allele frequency, the degree of sampling imbalanced, or the sample size. We focus on the type of population structure and propose a comparison of the most commonly used methods to deal with stratification that are the Genomic Control, Principal Component based methods such as implemented in Eigenstrat, adjusted Regressions and Meta-Analyses strategies. Our assessment of the methods is based on a large simulation study, involving several scenarios corresponding to many types of population structures. We focused on both false positive rate and power to determine which methods perform the best. Our analysis showed that if there is no population structure, none of the tests led to a bias nor decreased the power except for the Meta- Analyses. When the population is strati