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Harnessing multivariate, penalized regression methods for genomic prediction and QTL detection of drought-related traits in grapevine.

ABSTRACT: Viticulture has to cope with climate change and to decrease pesticide inputs, while maintaining yield and wine quality. Breeding is a key lever to meet this challenge, and genomic prediction a promising tool to accelerate breeding programs. Multivariate methods are potentially more accurate than univariate ones. Moreover, some prediction methods also provide marker selection, thus allowing quantitative trait loci (QTLs) detection and the identification of positional candidate genes. To study both genomic prediction and QTL detection for drought-related traits in grapevine, we applied several methods, interval mapping (IM) as well as univariate and multivariate penalized regression, in a bi-parental progeny. With a dense genetic map, we simulated two traits under four QTL configurations. The penalized regression method Elastic Net (EN) for genomic prediction, and controlling the marginal False Discovery Rate on EN selected markers to prioritize the QTLs. Indeed, penalized methods were more powerful than IM for QTL detection across various genetic architectures. Multivariate prediction did not perform better than its univariate counterpart, despite strong genetic correlation between traits. Using 14 traits measured in semi-controlled conditions under different watering conditions, penalized regression methods proved very efficient for intra-population prediction whatever the genetic architecture of the trait, with predictive abilities reaching 0.68. Compared to a previous study on the same traits, these methods applied on a denser map found new QTLs controlling traits linked to drought tolerance and provided relevant candidate genes. Overall, these findings provide a strong evidence base for implementing genomic prediction in grapevine breeding.

SUBMITTER: Brault C

PROVIDER: S-EPMC8496232 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Polygenic Risk Scores (PRS) combine genotype information across many single-nucleotide polymorphisms (SNPs) to give a score reflecting the genetic risk of developing a disease. PRS might have a major impact on public health, possibly allowing for screening campaigns to identify high-genetic risk individuals for a given disease. The "Clumping+Thresholding" (C+T) approach is the most common method to derive PRS. C+T uses only univariate genome-wide association studies (GWAS) summary statistics, which makes it fast and easy to use. However, previous work showed that jointly estimating SNP effects for computing PRS has the potential to significantly improve the predictive performance of PRS as compared to C+T. In this paper, we present an efficient method for the joint estimation of SNP effects using individual-level data, allowing for practical application of penalized logistic regression (PLR) on modern datasets including hundreds of thousands of individuals. Moreover, our implementation of PLR directly includes automatic choices for hyper-parameters. We also provide an implementation of penalized linear regression for quantitative traits. We compare the performance of PLR, C+T and a derivation of random forests using both real and simulated data. Overall, we find that PLR achieves equal or higher predictive performance than C+T in most scenarios considered, while being scalable to biobank data. In particular, we find that improvement in predictive performance is more pronounced when there are few effects located in nearby genomic regions with correlated SNPs; for instance, in simulations, AUC values increase from 83% with the best prediction of C+T to 92.5% with PLR. We confirm these results in a data analysis of a case-control study for celiac disease where PLR and the standard C+T method achieve AUC values of 89% and of 82.5%. Applying penalized linear regression to 350,000 individuals of the UK Biobank, we predict height with a larger correlation than with the best prediction of C+T (∼65% instead of ∼55%), further demonstrating its scalability and strong predictive power, even for highly polygenic traits. Moreover, using 150,000 individuals of the UK Biobank, we are able to predict breast cancer better than C+T, fitting PLR in a few minutes only. In conclusion, this paper demonstrates the feasibility and relevance of using penalized regression for PRS computation when large individual-level datasets are available, thanks to the efficient implementation available in our R package bigstatsr.

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Harnessing multivariate, penalized regression methods for genomic prediction and QTL detection of drought-related traits in grapevine.

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