Jun 12, 2016

The Heritability of Pathogen Traits: Definitions and Estimators

BioRxiv : the Preprint Server for Biology
Venelin Mitov, Tanja Stadler

Abstract

Pathogen traits, such as the virulence of an infection, can vary significantly between patients. A major challenge is to measure the extent to which genetic differences between infecting strains explain the observed variation of the trait. This is quantified by the trait's broad-sense heritability, H2. A recent discrepancy between estimates of the heritability of HIV-virulence has opened a debate on the estimators' accuracy. Here, we show that the discrepancy originates from model limitations and important lifecycle differences between sexually reproducing organisms and transmittable pathogens. In particular, current quantitative genetics methods, such as donor-recipient regression (DR) of surveyed serodiscordant couples and the phylogenetic mixed model (PMM), are prone to underestimate H2, because they fail to model the gradual loss of phenotypic resemblance between transmission-related patients in the presence of within-host evolution. We explore two approaches correcting these errors: ANOVA on closest phylogenetic pairs (ANOVA-CPP) and the phylogenetic Ornstein-Uhlenbeck mixed model (POUMM). Empirical analyses reveal that at least 25% of the variation in HIV-virulence is explained by the virus genome both for European and Af...Continue Reading

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Mentioned in this Paper

Neuro-Oncological Ventral Antigen 2
Genome-Wide Association Study
Study
Virus
Genome
Pathogenic Organism
Definition
Phylogenetic Analysis
HIV Infections
NOVA2 protein, human

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