Extensive impact of low-frequency variants on the phenotypic landscape at population-scale

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 i...

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Bibliographic Details
Main Authors: Téo Fournier, Omar Abou Saada, Jing Hou, Jackson Peter, Elodie Caudal, Joseph Schacherer
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2019-10-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/49258
Description
Summary: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.
ISSN:2050-084X