title: Accounting for genetic architecture improves sequence based genomic prediction for a Drosophila fitness trait.
abstract: The ability to predict quantitative trait phenotypes from molecular polymorphism data will revolutionize evolutionary biology, medicine and human biology, and animal and plant breeding. Efforts to map quantitative trait loci have yielded novel insights into the biology of quantitative traits, but the combination of individually significant quantitative trait loci typically has low predictive ability. Utilizing all segregating variants can give good predictive ability in plant and animal breeding populations, but gives little insight into trait biology. Here, we used the Drosophila Genetic Reference Panel to perform both a genome wide association analysis and genomic prediction for the fitness-related trait chill coma recovery time. We found substantial total genetic variation for chill coma recovery time, with a genetic architecture that differs between males and females, a small number of molecular variants with large main effects, and evidence for epistasis. Although the top additive variants explained 36% (17%) of the genetic variance among lines in females (males), the predictive ability using genomic best linear unbiased prediction and a relationship matrix using all common segregating variants was very low for females and zero for males. We hypothesized that the low predictive ability was due to the mismatch between the infinitesimal genetic architecture assumed by the genomic best linear unbiased prediction model and the true genetic architecture of chill coma recovery time. Indeed, we found that the predictive ability of the genomic best linear unbiased prediction model is markedly improved when we combine quantitative trait locus mapping with genomic prediction by only including the top variants associated with main and epistatic effects in the relationship matrix. This trait-associated prediction approach has the advantage that it yields biologically interpretable prediction models.
authors.affiliation: Department of Animal Sciences, Animal Breeding and Genetics Group, Georg-August-Universität Göttingen, Göttingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Ober
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, United States of America.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Magwire
authors.affiliation: Institute for Mathematics, University of Mannheim, Mannheim, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schlather
authors.affiliation: Department of Animal Sciences, Animal Breeding and Genetics Group, Georg-August-Universität Göttingen, Göttingen, Germany.
authors.forename: Henner
authors.initials: H
authors.lastname: Simianer
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, United States of America.
authors.forename: Trudy F C
authors.initials: TF
authors.lastname: Mackay
mesh_terms: D000818:Animals; D004330:Drosophila / Q000235:genetics* / Q000502:physiology*; D017344:Genes, Insect