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Local and Bayesian Survival FDR Estimations to Identify Reliable Associations in Whole Genome of Bread Wheat

Estimating the FDR significance threshold in genome-wide association studies remains a major challenge in distinguishing true positive hypotheses from false positive and negative errors. Several comparative methods for multiple testing comparison have been developed to determine the significance thr...

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Autores principales: Sadeqi, Mohammad Bahman, Ballvora, Agim, Léon, Jens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531084/
https://www.ncbi.nlm.nih.gov/pubmed/37762314
http://dx.doi.org/10.3390/ijms241814011
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author Sadeqi, Mohammad Bahman
Ballvora, Agim
Léon, Jens
author_facet Sadeqi, Mohammad Bahman
Ballvora, Agim
Léon, Jens
author_sort Sadeqi, Mohammad Bahman
collection PubMed
description Estimating the FDR significance threshold in genome-wide association studies remains a major challenge in distinguishing true positive hypotheses from false positive and negative errors. Several comparative methods for multiple testing comparison have been developed to determine the significance threshold; however, these methods may be overly conservative and lead to an increase in false negative results. The local FDR approach is suitable for testing many associations simultaneously based on the empirical Bayes perspective. In the local FDR, the maximum likelihood estimator is sensitive to bias when the GWAS model contains two or more explanatory variables as genetic parameters simultaneously. The main criticism of local FDR is that it focuses only locally on the effects of single nucleotide polymorphism (SNP) in tails of distribution, whereas the signal associations are distributed across the whole genome. The advantage of the Bayesian perspective is that knowledge of prior distribution comes from other genetic parameters included in the GWAS model, such as linkage disequilibrium (LD) analysis, minor allele frequency (MAF) and call rate of significant associations. We also proposed Bayesian survival FDR to solve the multi-collinearity and large-scale problems, respectively, in grain yield (GY) vector in bread wheat with large-scale SNP information. The objective of this study was to obtain a short list of SNPs that are reliably associated with GY under low and high levels of nitrogen (N) in the population. The five top significant SNPs were compared with different Bayesian models. Based on the time to events in the Bayesian survival analysis, the differentiation between minor and major alleles within the association panel can be identified.
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spelling pubmed-105310842023-09-28 Local and Bayesian Survival FDR Estimations to Identify Reliable Associations in Whole Genome of Bread Wheat Sadeqi, Mohammad Bahman Ballvora, Agim Léon, Jens Int J Mol Sci Article Estimating the FDR significance threshold in genome-wide association studies remains a major challenge in distinguishing true positive hypotheses from false positive and negative errors. Several comparative methods for multiple testing comparison have been developed to determine the significance threshold; however, these methods may be overly conservative and lead to an increase in false negative results. The local FDR approach is suitable for testing many associations simultaneously based on the empirical Bayes perspective. In the local FDR, the maximum likelihood estimator is sensitive to bias when the GWAS model contains two or more explanatory variables as genetic parameters simultaneously. The main criticism of local FDR is that it focuses only locally on the effects of single nucleotide polymorphism (SNP) in tails of distribution, whereas the signal associations are distributed across the whole genome. The advantage of the Bayesian perspective is that knowledge of prior distribution comes from other genetic parameters included in the GWAS model, such as linkage disequilibrium (LD) analysis, minor allele frequency (MAF) and call rate of significant associations. We also proposed Bayesian survival FDR to solve the multi-collinearity and large-scale problems, respectively, in grain yield (GY) vector in bread wheat with large-scale SNP information. The objective of this study was to obtain a short list of SNPs that are reliably associated with GY under low and high levels of nitrogen (N) in the population. The five top significant SNPs were compared with different Bayesian models. Based on the time to events in the Bayesian survival analysis, the differentiation between minor and major alleles within the association panel can be identified. MDPI 2023-09-12 /pmc/articles/PMC10531084/ /pubmed/37762314 http://dx.doi.org/10.3390/ijms241814011 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sadeqi, Mohammad Bahman
Ballvora, Agim
Léon, Jens
Local and Bayesian Survival FDR Estimations to Identify Reliable Associations in Whole Genome of Bread Wheat
title Local and Bayesian Survival FDR Estimations to Identify Reliable Associations in Whole Genome of Bread Wheat
title_full Local and Bayesian Survival FDR Estimations to Identify Reliable Associations in Whole Genome of Bread Wheat
title_fullStr Local and Bayesian Survival FDR Estimations to Identify Reliable Associations in Whole Genome of Bread Wheat
title_full_unstemmed Local and Bayesian Survival FDR Estimations to Identify Reliable Associations in Whole Genome of Bread Wheat
title_short Local and Bayesian Survival FDR Estimations to Identify Reliable Associations in Whole Genome of Bread Wheat
title_sort local and bayesian survival fdr estimations to identify reliable associations in whole genome of bread wheat
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531084/
https://www.ncbi.nlm.nih.gov/pubmed/37762314
http://dx.doi.org/10.3390/ijms241814011
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