Novel Statistical Methods in Quantitative Genetics: Modeling Genetic Variance for Quantitative Trait Loci Mapping and Genomic Evaluation
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
This thesis develops and evaluates statistical methods for different types of genetic analyses, including quantitative trait loci (QTL) analysis, genome-wide association study (GWAS), and genomic evaluation. The main contribution of the thesis is to provide novel insights in modeling genetic variance, especially via random effects models.
In variance component QTL analysis, a full likelihood model accounting for uncertainty in the identity-by-descent (IBD) matrix was developed. It was found to be able to correctly adjust the bias in genetic variance component estimation and gain power in QTL mapping in terms of precision.
Double hierarchical generalized linear models, and a non-iterative simplified version, were implemented and applied to fit data of an entire genome. These whole genome models were shown to have good performance in both QTL mapping and genomic prediction.
A re-analysis of a publicly available GWAS data set identified significant loci in Arabidopsis that control phenotypic variance instead of mean, which validated the idea of variance-controlling genes.
The works in the thesis are accompanied by R packages available online, including a general statistical tool for fitting random effects models (hglm), an efficient generalized ridge regression for high-dimensional data (bigRR), a double-layer mixed model for genomic data analysis (iQTL), a stochastic IBD matrix calculator (MCIBD), a computational interface for QTL mapping (qtl.outbred), and a GWAS analysis tool for mapping variance-controlling loci (vGWAS).
Place, publisher, year, edition, pages
Uppsala: Uppsala universitet, 2012.
, Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 908
statistical genetics, quantitative trait loci, genome-wide association study, genomic selection, genetic variance, hierarchical generalized linear model, linear mixed model, random effect, heteroscedastic effects model, variance-controlling genes
Probability Theory and Statistics
Research subject Komplexa system - mikrodataanalys
IdentifiersURN: urn:nbn:se:du-11673ISBN: 978-91-554-8298-5OAI: oai:DiVA.org:du-11673DiVA: diva2:586378
Carlborg, ÖrjanRönnegård, Lars, docent