A multilocus association analysis method integrating phenotype and expression data reveals multiple novel associations to flowering time variation in wild-collected Arabidopsis thaliana.

The adaptation to a new habitat often results in a confounding between genomewide genotype and beneficial alleles. When the confounding is strong, or the allelic effects is weak, it is a major statistical challenge to detect the adaptive polymorphisms. We describe a novel approach to dissect polygenic traits in natural populations. First, candidate adaptive loci are identified by screening for loci directly associated with the adaptive trait or the expression of genes known to affect it. Then, a multilocus genetic architecture is inferred using a backward elimination association analysis across all candidate loci with an adaptive false discovery rate-based threshold. Effects of population stratification are controlled by accounting for genomic kinship in both steps of the analysis and also by simultaneously testing all candidate loci in the multilocus model. We illustrate the method by exploring the polygenic basis of an important adaptive trait, flowering time in Arabidopsis thaliana, using public data from the 1,001 genomes project. We revealed associations between 33 (29) loci and flowering time at 10 (16)°C in this collection of natural accessions, where standard genomewide association analysis methods detected five (3) loci. The 33 (29) loci explained approximately 55.1 (48.7)% of the total phenotypic variance of the respective traits. Our work illustrates how the genetic basis of highly polygenic adaptive traits in natural populations can be explored in much greater detail using new multilocus mapping approaches taking advantage of prior biological information, genome and transcriptome data.