Genome-wide association mapping including phenotypes from relatives without genotypes

作者：H. Wang, I. Misztal, Ignácio Aguilar, Andrés Legarra, William M. Muir · 发表于：Genetics Research · 年份：2012 · DOI：10.1017/s0016672312000274 · 被引用次数：670 · 研究领域：Genetic and phenotypic traits in livestock、Genetic Mapping and Diversity in Plants and Animals、Genetics and Plant Breeding

A common problem for genome-wide association analysis (GWAS) is lack of power for detection of quantitative trait loci (QTLs) and precision for fine mapping. Here, we present a statistical method, termed single-step GBLUP (ssGBLUP), which increases both power and precision without increasing genotyping costs by taking advantage of phenotypes from other related and unrelated subjects. The procedure achieves these goals by blending traditional pedigree relationships with those derived from genetic markers, and by conversion of estimated breeding values (EBVs) to marker effects and weights. Additionally, the application of mixed model approaches allow for both simple and complex analyses that involve multiple traits and confounding factors, such as environmental, epigenetic or maternal environmental effects. Efficiency of the method was examined using simulations with 15,800 subjects, of which 1500 were genotyped. Thirty QTLs were simulated across genome and assumed heritability was 0·5. Comparisons included ssGBLUP applied directly to phenotypes, BayesB and classical GWAS (CGWAS) with deregressed proofs. An average accuracy of prediction 0·89 was obtained by ssGBLUP after one iteration, which was 0·01 higher than by BayesB. Power and precision for GWAS applications were evaluated by the correlation between true QTL effects and the sum of m adjacent single nucleotide polymorphism (SNP) effects. The highest correlations were 0·82 and 0·74 for ssGBLUP and CGWAS with m=8, and 0·83 ...