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Mixed Logistic Regression in Genome-Wide Association Studies

View ORCID ProfileJacqueline Milet, View ORCID ProfileHervé Perdry
doi: https://doi.org/10.1101/2020.01.17.910109
Jacqueline Milet
1Université de Paris, MERIT, IRD, Paris, F-75006, France
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  • ORCID record for Jacqueline Milet
Hervé Perdry
2CESP Inserm, U1018, UFR Médecine, Univ Paris-Sud, Université Paris-Saclay, Villejuif, France
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Abstract

Motivation Mixed linear models (MLM) have been widely used to account for population structure in case-control genome-wide association studies, the status being analyzed as a quantitative phenotype. Chen et al. proved that this method is inappropriate and proposed a score test for the mixed logistic regression (MLR). However this test does not allow an estimation of the variants’ effects.

Results We propose two computationally efficient methods to estimate the variants’ effects. Their properties are evaluated on two simulations sets, and compared with other methods (MLM, logistic regression). MLR performs the best in all circumstances. The variants’ effects are well evaluated by our methods, with a moderate bias when the effect sizes are large. Additionally, we propose a stratified QQ-plot, enhancing the diagnosis of p-values inflation or deflation, when population strata are not clearly identified in the sample.

Availability All methods are implemented in the R package milorGWAS available at https://github.com/genostats/milorGWAS.

Contact herve.perdry{at}u-psud.fr

Supplementary information Supplementary data are available at Bioinformatics online.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 17, 2020.
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Mixed Logistic Regression in Genome-Wide Association Studies
Jacqueline Milet, Hervé Perdry
bioRxiv 2020.01.17.910109; doi: https://doi.org/10.1101/2020.01.17.910109
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Mixed Logistic Regression in Genome-Wide Association Studies
Jacqueline Milet, Hervé Perdry
bioRxiv 2020.01.17.910109; doi: https://doi.org/10.1101/2020.01.17.910109

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