Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setup. Retrovirology
Parent-offspring (PO) regression is a central tool to determine the heritability of phenotypic traits; i.e., the relative extent to which those traits are controlled by genetic factors. The applicability of PO regression to viral traits is unclear because the direction of viral transmission – who is the donor (parent) and who is the recipient (offspring) – is typically unknown and viral phylogenies are sparsely sampled.
Using simulated data on phylogenies derived from 11’442 Swiss HIV Cohort Study (SHCS) partial pol sequences and set-point viral load (SPVL) data from 3’293 patients, Bachmann et al. tested PO regression robustness against both the lack of knowledge concerning transmission directionality and sparse sampling. The authors found that the misidentification of donor and recipient plays a minor role in estimating heritability and showed that sparse sampling does not influence the mean heritability estimated by PO regression. A mixed-effect model with pairs as groups yielded heritability estimates equivalent to PO regression. Using both methods to estimate SPVL heritability in the SHCS, they employed a wide range of transmission pair criteria to measure heritability and found a strong dependence of the heritability estimates to these criteria. However, the estimates did not change substantially after adjusting for host-demographic factors in the mixed-effect model.
In conclusion, the study-results suggest that PO regression is for conservative transmission pair criteria a robust estimator of heritability in large datasets and that its conceptual problems are not quantitatively relevant in a real-life setting. Overall, the study found a strong effect of viral genetics on SPVL (32-46%) that is not confounded by host demographics.