TY - JOUR TI - Extensive impact of low-frequency variants on the phenotypic landscape at population-scale AU - Fournier, Téo AU - Abou Saada, Omar AU - Hou, Jing AU - Peter, Jackson AU - Caudal, Elodie AU - Schacherer, Joseph A2 - Landry, Christian R A2 - Barkai, Naama VL - 8 PY - 2019 DA - 2019/10/24 SP - e49258 C1 - eLife 2019;8:e49258 DO - 10.7554/eLife.49258 UR - https://doi.org/10.7554/eLife.49258 AB - Genome-wide association studies (GWAS) allow to dissect complex traits and map genetic variants, which often explain relatively little of the heritability. One potential reason is the preponderance of undetected low-frequency variants. To increase their allele frequency and assess their phenotypic impact in a population, we generated a diallel panel of 3025 yeast hybrids, derived from pairwise crosses between natural isolates and examined a large number of traits. Parental versus hybrid regression analysis showed that while most phenotypic variance is explained by additivity, a third is governed by non-additive effects, with complete dominance having a key role. By performing GWAS on the diallel panel, we found that associated variants with low frequency in the initial population are overrepresented and explain a fraction of the phenotypic variance as well as an effect size similar to common variants. Overall, we highlighted the relevance of low-frequency variants on the phenotypic variation. KW - genetic architecture KW - GWAS KW - low-frequency variants JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -