An efficient approach to large-scale genotype-phenotype association analyses.

ABSTRACT

Modern molecular biotechnology generates a great deal of intermediate information, such as transcriptional and metabolic products in bridging DNA and complex traits. In genome-wide linkage analysis and genome-wide association study, regression analysis for large-scale correlated phenotypes is applied to map genes for those by-products that are regarded as quantitative traits. For a single trait, least absolute shrinkage and selection operator with coordinate descent step can be employed to efficiently shrink sparse non-zero genetic effects of quantitative trait loci (QTLs). However, regression analyses in a trait-by-trait basis do not take account of the correlations among the analyzed traits. In this study, conditional phenotype of each trait is defined, given other traits. Large-scale genotype-phenotype association analyses are therefore transformed to separate genotype-conditional phenotype ones. Meanwhile, the correlation architecture between each trait and other traits can also be provided by shrinkage estimation for each conditional phenotype. Simulation demonstrates that the proposed conditional mapping method is generally identical to joint mapping method based on multivariate analysis in terms of statistical detection power and parameter estimation. Application of the method is provided to locate eQTL in yeast.