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Genome-Wide Association with Uncertainty in the Genetic Similarity Matrix

Wang, Shijia; Ge, Shufei; Sobkowiak, Benjamin; Wang, Liangliang; Grandjean, Louis; Colijn, Caroline; Elliott, Lloyd T; (2022) Genome-Wide Association with Uncertainty in the Genetic Similarity Matrix. Journal of Computational Biology 10.1089/cmb.2022.0067. (In press). Green open access

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Abstract

Genome-wide association studies (GWASs) are often confounded by population stratification and structure. Linear mixed models (LMMs) are a powerful class of methods for uncovering genetic effects, while controlling for such confounding. LMMs include random effects for a genetic similarity matrix, and they assume that a true genetic similarity matrix is known. However, uncertainty about the phylogenetic structure of a study population may degrade the quality of LMM results. This may happen in bacterial studies in which the number of samples or loci is small, or in studies with low-quality genotyping. In this study, we develop methods for linear mixed models in which the genetic similarity matrix is unknown and is derived from Markov chain Monte Carlo estimates of the phylogeny. We apply our model to a GWAS of multidrug resistance in tuberculosis, and illustrate our methods on simulated data.

Type: Article
Title: Genome-Wide Association with Uncertainty in the Genetic Similarity Matrix
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1089/cmb.2022.0067
Publisher version: https://doi.org/10.1089/cmb.2022.0067
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: genetic similarity, genome-wide association studies, phylogenetics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10161374
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