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Optimal experimental designs for estimating genetic and non-genetic effects underlying infectious disease transmission

View ORCID ProfileChristopher Pooley, View ORCID ProfileGlenn Marion, Stephen Bishop, Andrea Doeschl-Wilson
doi: https://doi.org/10.1101/2022.01.10.475628
Christopher Pooley
1Biomathematics and Statistics Scotland, James Clerk Maxwell Building, The King’s Buildings, Peter Guthrie Tait Road, Edinburgh, EH9 3FD, UK
2The Roslin Institute, University of Edinburgh, Midlothian, EH25 9RG, UK
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  • For correspondence: chris.pooley@bioss.ac.uk
Glenn Marion
1Biomathematics and Statistics Scotland, James Clerk Maxwell Building, The King’s Buildings, Peter Guthrie Tait Road, Edinburgh, EH9 3FD, UK
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Stephen Bishop
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Andrea Doeschl-Wilson
2The Roslin Institute, University of Edinburgh, Midlothian, EH25 9RG, UK
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Abstract

Background Infectious disease spread in populations is controlled by individuals’ susceptibility (propensity to acquire infection), infectivity (propensity to pass on infection to others) and recoverability (propensity to recover/die). Estimating the effects of genetic risk factors on these host epidemiological traits can help reduce disease spread through genetic control strategies. However, the effects of previously identified ‘disease resistance SNPs’ on these epidemiological traits are usually unknown. Recent advances in computational statistics make it now possible to estimate the effects of single nucleotide polymorphisms (SNPs) on these traits from longitudinal epidemic data (e.g. infection and/or recovery times of individuals or diagnostic test results). However, little is known how to optimally design disease transmission experiments or field studies to maximise the precision at which pleiotropic SNP effects estimates for susceptibility, infectivity and recoverability can be estimated.

Results We develop and validate analytical expressions for the precision of SNP effects estimates on the three host traits assuming a disease transmission experiment with one or more non-interacting contact groups. Maximising these leads to three distinct ‘experimental’ designs, each specifying a different set of ideal SNP genotype compositions across groups: a) appropriate for a single contact-group, b) a multi-group design termed “pure”, and c) a multi-group design termed “mixed”, where ‘pure’ and ‘mixed’ refer to contact groups consisting of individuals with the same or different SNP genotypes, respectively. Precision estimates for susceptibility and recoverability were found to be less sensitive to the experimental design than infectivity. Data from multiple groups were found more informative about infectivity effects than from a single group containing the same number of individuals. Whilst the analytical expressions suggest that the multi-group pure and mixed designs estimate SNP effects with similar precision, the mixed design is preferable because it uses information from naturally occurring infections rather than those artificially induced. The same optimal design principles apply to estimating other categorical fixed effects, such as vaccinations status, helping to more effectively quantify their epidemiological impact.

An online software tool SIRE-PC has been developed which calculates the precision of estimated substitution and dominance effects of a single SNP (or vaccine status) associated with all three traits depending on experimental design parameters.

Conclusions The developed methodology and software tool can be used to aid the design of disease transmission experiments for estimating the effect of individual SNPs and other categorical variables underlying host susceptibility, infectivity and recoverability.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • E-mail addresses: GM: glenn.marion{at}bioss.ac.uk, AW: andrea.wilson{at}roslin.ed.ac.uk

  • https://theiteam.github.io/SIRE-PC.html

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 4.0 International license.
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Posted January 11, 2022.
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Optimal experimental designs for estimating genetic and non-genetic effects underlying infectious disease transmission
Christopher Pooley, Glenn Marion, Stephen Bishop, Andrea Doeschl-Wilson
bioRxiv 2022.01.10.475628; doi: https://doi.org/10.1101/2022.01.10.475628
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Optimal experimental designs for estimating genetic and non-genetic effects underlying infectious disease transmission
Christopher Pooley, Glenn Marion, Stephen Bishop, Andrea Doeschl-Wilson
bioRxiv 2022.01.10.475628; doi: https://doi.org/10.1101/2022.01.10.475628

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