Comparison of mixed-model approaches for association mapping

Genetics. 2008 Mar;178(3):1745-54. doi: 10.1534/genetics.107.079707. Epub 2008 Feb 3.

Abstract

Association-mapping methods promise to overcome the limitations of linkage-mapping methods. The main objectives of this study were to (i) evaluate various methods for association mapping in the autogamous species wheat using an empirical data set, (ii) determine a marker-based kinship matrix using a restricted maximum-likelihood (REML) estimate of the probability of two alleles at the same locus being identical in state but not identical by descent, and (iii) compare the results of association-mapping approaches based on adjusted entry means (two-step approaches) with the results of approaches in which the phenotypic data analysis and the association analysis were performed in one step (one-step approaches). On the basis of the phenotypic and genotypic data of 303 soft winter wheat (Triticum aestivum L.) inbreds, various association-mapping methods were evaluated. Spearman's rank correlation between P-values calculated on the basis of one- and two-stage association-mapping methods ranged from 0.63 to 0.93. The mixed-model association-mapping approaches using a kinship matrix estimated by REML are more appropriate for association mapping than the recently proposed QK method with respect to (i) the adherence to the nominal alpha-level and (ii) the adjusted power for detection of quantitative trait loci. Furthermore, we showed that our data set could be analyzed by using two-step approaches of the proposed association-mapping method without substantially increasing the empirical type I error rate in comparison to the corresponding one-step approaches.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Chromosome Mapping / methods*
  • Models, Genetic*
  • Principal Component Analysis
  • Quantitative Trait Loci / genetics
  • Statistics, Nonparametric
  • Triticum / genetics*