Risk ratio as parameter for the genetic characterization of complex binary traits in cattle. A simulation study under various genetic models using halfsib families

The risk ratio (λ_R) is defined as ‘the recurrence risk for a relative of an affected individual divided by the prevalence in the general population’ and is considered as the most important parameter when designing mapping experiments for diseases in humans. In this paper, the risk ratio was introduced as a parameter to genetically characterize complex binary traits such as mastitis in cattle. Simulations were applied to evaluate the properties of λ_R under different genetic models (monogenic, digenic, polygenic and mixed models) and in dependency of their parameters for a design consisting of unbalanced halfsib families typically found in dairy cattle. Population prevalences of the simulated data ranged from 5 to 40% and λ_R was estimated on a phenotypic level. In the discrete loci models complexity of the traits was introduced through different levels of penetrance and the proportions of phenocopies within each genetic background. The risk ratio and the power to reject the null hypothesis of independent halfsibs (λ_R=1) were influenced by the prevalence in all genetic models chosen. Absolute values for λ_R were higher for lower prevalences, for example, λ_R=2.77 and 1.62 for a pure monogenic recessive model with 5 and 20% prevalence, respectively, whereas the power decreases in the case of lower prevalences. For all the prevalences investigated, higher risk ratios were found for discrete loci models compared with the polygenic models, with higher values for the monogenic relative to the digenic models in general. For the mixed models, λ_R was intermediate between the polygenic and discrete loci models. Genes with dominant relative to recessive inheritance for susceptibility caused higher risk ratios in monogenic and mixed models, for example, λ_R=5.16 and 2.77 for a pure monogenic model with 5% prevalence. In the discrete loci models, λ_R decreased with lower penetrance and a higher proportion of phenocopies. Risk ratios increased with the heritability in the polygenic and in addition with the effect of the major gene in mixed models. Consistent patterns of risk ratios were observed under the analysed genetic models and parameters, which indicate that the risk ratio is a parameter well suited to genetically characterize binary traits in unbalanced halfsib families.