Recent research has developed various promising methods to control for population structure in genomewide association mapping of complex traits, but systematic examination of how well these methods perform under different genetic scenarios is still lacking. Appropriate methods for controlling genetic relationships among individuals need to balance the concern of false positives and statistical power, which can vary for different association sample types. We used a series of simulated samples and empirical data sets from cross-and self-pollinated species to demonstrate the performance of several contemporary methods in correcting for different types of genetic relationships encountered in association analysis. We proposed a two-stage dimension determination approach for both principal component analysis and nonmetric multidimensional scaling (nMDS) to capture the major structure pattern in association mapping samples. Our results showed that by exploiting both genotypic and phenotypic information, this two-stage dimension determination approach balances the trade-off between data fit and model complexity, resulting in an effective reduction in false positive rate with minimum loss in statistical power. Further, the nMDS technique of correcting for genetic relationship proved to be a powerful complement to other existing methods. Our findings highlight the significance of appropriate application of different statistical methods for dealing with complex genetic relationships in various genomewide association studies.A SSOCIATION mapping of genetic factors underlying major human diseases has yielded very promising results, demonstrating the power of both genomewide and candidate-gene association mapping approaches (Newport et al. 2007;Samani et al. 2007;Scott et al. 2007; Wellcome Trust Case Control Consortium 2007;Yeager et al. 2007). Significant reductions in the costs of sequencing and genotyping make it feasible to conduct association mapping studies in many other species (Thornsberry et al. 2001;Aranzana et al. 2005;Borevitz et al. 2007;Clark et al. 2007). However, one obstacle inherent to drawing causal inferences from earlier association studies is the confounding effect of population structure (Lander and Kruglyak 1995;Marchini et al. 2004;Hirschhorn and Daly 2005;Wang et al. 2005;Shriner et al. 2007). Because this effect generally increases in proportion to population size (Reich and Lander 2001), population structure remains a major concern in large-scale association analyses (McCarthy et al. 2008).Several methods have been proposed for using association mapping in populations with complex genetic structure. Besides the earlier methods of genomic control (Devlin and Roeder 1999;Devlin et al. 2004) and structured association based on Bayesian clustering Falush et al. 2003Falush et al. , 2007, principal component analysis (PCA) was recently suggested as a fast and effective way to diagnose population structure (Price et al. 2006;Patterson et al. 2007). The PCA method summarizes variation observed a...