Extensive impact of low-frequency variants on the phenotypic landscape at population-scale
Abstract
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 3,025 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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1 and 4.
Article and author information
Author details
Funding
National Institutes of Health (R01 GM101091-01)
- Joseph Schacherer
European Research Council (Consolidator grants (772505))
- Joseph Schacherer
Fondation pour la Recherche Médicale (Graduate student grant)
- Téo Fournier
Institut Universitaire de France
- Joseph Schacherer
University of Strasbourg Institute for Advanced Study
- Joseph Schacherer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Christian R Landry, Université Laval, Canada
Version history
- Received: June 12, 2019
- Accepted: October 23, 2019
- Accepted Manuscript published: October 24, 2019 (version 1)
- Version of Record published: December 4, 2019 (version 2)
Copyright
© 2019, Fournier et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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- Genetics and Genomics
Rare genetic variants in yeast explain a large amount of phenotypic variation in a complex trait like growth.
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- Genetics and Genomics
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