A Practical Guide to Estimating the Heritability of Pathogen Traits.

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 of surveyed serodiscordant couples and the phylogenetic mixed model (PMM), are prone to underestimate H2, because they neglect or do not fit to the loss of resemblance between transmission partners caused by within-host evolution. In a phylogenetic analysis of 8,483 HIV patients from the United Kingdom, we show that the phenotypic correlation between transmission partners decays with the amount of within-host evolution of the virus. We reproduce this pattern in toy-model simulations and show that a phylogenetic Ornstein-Uhlenbeck model (POUMM) outperforms the PMM in capturing this correlation pattern and in quantifying H2. In particular, we show that POUMM outperforms PMM even in simulations without selection-as it captures the mentioned correlation pattern-which has not been appreciated until now. By cross-validating the POUMM estimates with ANOVA on closest phylogenetic pairs, we obtain H2 ? 0.2, meaning ?20% of the variation in HIV-virulence is explained by the virus genome both for European and African data.

SUBMITTER: Mitov V 

PROVIDER: S-EPMC5850476 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature