Estimates Of Indirect Genetic Effects Research Articles

Interpreting population- and family-based genome-wide association studies in the presence of confounding.

A central aim of genome-wide association studies (GWASs) is to estimate direct genetic effects: the causal effects on an individual's phenotype of the alleles that they carry. However, estimates of direct effects can be subject to genetic and environmental confounding and can also absorb the "indirect" genetic effects of relatives' genotypes. Recently, an important development in controlling for these confounds has been the use of within-family GWASs, which, because of the randomness of mendelian segregation within pedigrees, are often interpreted as producing unbiased estimates of direct effects. Here, we present a general theoretical analysis of the influence of confounding in standard population-based and within-family GWASs. We show that, contrary to common interpretation, family-based estimates of direct effects can be biased by genetic confounding. In humans, such biases will often be small per-locus, but can be compounded when effect-size estimates are used in polygenic scores (PGSs). We illustrate the influence of genetic confounding on population- and family-based estimates of direct effects using models of assortative mating, population stratification, and stabilizing selection on GWAS traits. We further show how family-based estimates of indirect genetic effects, based on comparisons of parentally transmitted and untransmitted alleles, can suffer substantial genetic confounding. We conclude that, while family-based studies have placed GWAS estimation on a more rigorous footing, they carry subtle issues of interpretation that arise from confounding.

The predictive ability of indirect genetic models is reduced when culled animals are omitted from the data

BackgroundPhysical removal of individuals from groups causes reductions in group sizes and changes in group composition, which may affect the predictive ability of estimates of indirect genetic effects of animals on phenotypes of group mates. We hypothesized that including indirect genetic effects of culled animals and of animals without phenotypes in the analysis affects estimates of genetic parameters, improves predictive ability, and reduces bias of predicted breeding values. We tested this by applying different editing procedures, i.e. omission of individuals or groups from the data, and genetic models, i.e. a classical and an indirect genetic model (IGM) without or with weighting of indirect genetic effects based on the relative proportion of time spent in the pen or space allowance. Data consisted of average daily gain for 123,567 pigs in 11,111 groups, from which 3% of individuals in 25% of groups were prematurely removed from the group.ResultsThe estimate of total heritability was higher (0.29 to 0.34) than that of direct heritability (0.23 to 0.25) regardless of the editing procedures and IGM used. Omission of individuals or groups from the data reduced the predictive ability of estimates of indirect genetic effects by 8 to 46%, and the predictive ability of estimates of the combined direct and indirect genetic effects by up to 4%. Omission of full groups introduced bias in predicted breeding values. Weighting of indirect genetic effects reduced the predictive ability of their estimates by at least 19% and of the estimates of the combined direct and indirect genetic effects by 1%.ConclusionsWe identified significant indirect genetic effects for growth in pigs. Culled animals should neither be removed from the data nor accounted for by weighting their indirect genetic effects in the model based on the relative proportion of time spent in the pen or space allowance, because it will reduce predictive ability and increase bias of predicted breeding values. Information on culled animals is important for prediction of indirect genetic effects and must be accounted for in IGM analyses by including fixed regressions based on relative time spent within the pen or relative space allowance.

Social effects of territorial neighbours on the timing of spring breeding in North American red squirrels.

Organisms can affect one another's phenotypes when they socially interact. Indirect genetic effects occur when an individual's phenotype is affected by genes expressed in another individual. These heritable effects can enhance or reduce adaptive potential, thereby accelerating or reversing evolutionary change. Quantifying these social effects is therefore crucial for our understanding of evolution, yet estimates of indirect genetic effects in wild animals are limited to dyadic interactions. We estimated indirect phenotypic and genetic effects, and their covariance with direct effects, for the date of spring breeding in North American red squirrels (Tamiasciurus hudsonicus) living in an array of territories of varying spatial proximity. Additionally, we estimated indirect effects and the strength of selection at low and high population densities. Social effects of neighbours on the date of spring breeding were different from zero at high population densities but not at low population densities. Indirect phenotypic effects accounted for a larger amount of variation in the date of breeding than differences attributable to the among-individual variance, suggesting social interactions are important for determining breeding dates. The genetic component to these indirect effects was however not statistically significant. We therefore showcase a powerful and flexible method that will allow researchers working in organisms with a range of social systems to estimate indirect phenotypic and genetic effects, and demonstrate the degree to which social interactions can influence phenotypes, even in a solitary species.

Estimation of indirect genetic effects in group‐housed mink (Neovison vison) should account for systematic interactions either due to kin or sex

Social interactions among individuals are abundant, both in wild and in domestic populations. With social interactions, the genes of an individual may affect the trait values of other individuals, a phenomenon known as indirect genetic effects (IGEs). IGEs can be estimated using linear mixed models. Most IGE models assume that individuals interact equally to all group mates irrespective of relatedness. Kin selection theory, however, predicts that an individual will interact differently with family members versus non-family members. Here, we investigate kin- and sex-specific non-genetic social interactions in group-housed mink. Furthermore, we investigated whether systematic non-genetic interactions between kin or individuals of the same sex influence the estimates of genetic parameters. As a second objective, we clarify the relationship between estimates of the traditional IGE model and a family-based IGE model proposed in a previous study. Our results indicate that male siblings in mink show different non-genetic interactions than female siblings in mink and that this may impact the estimation of genetic parameters. Moreover, we have shown how estimates from a family-based IGE model can be translated to the ordinary direct-indirect model and vice versa. We find no evidence for genetic differences in interactions among related versus unrelated mink.