Estimation of Parental Effects Using Polygenic Scores.

Offspring resemble their parents for both genetic and environmental reasons. Understanding the relative magnitude of these alternatives has long been a core interest in behavioral genetics research, but traditional designs, which compare phenotypic covariances to make inferences about unmeasured genetic and environmental factors, have struggled to disentangle them. Recently, Kong et al. (2018) showed that by correlating offspring phenotypic values with the measured polygenic score of parents' nontransmitted alleles, one can estimate the effect of "genetic nurture"-a type of passive gene-environment covariation that arises when heritable parental traits directly influence offspring traits. Here, we instantiate this basic idea in a set of causal models that provide novel insights into the estimation of parental influences on offspring. Most importantly, we show how jointly modeling the parental polygenic scores and the offspring phenotypes can provide an unbiased estimate of the variation attributable to the environmental influence of parents on offspring, even when the polygenic score accounts for a small fraction of trait heritability. This model can be further extended to (a) account for the influence of different types of assortative mating, (b) estimate the total variation due to additive genetic effects and their covariance with the familial environment (i.e., the full genetic nurture effect), and (c) model situations where a parental trait influences a different offspring trait. By utilizing structural equation modeling techniques developed for extended twin family designs, our approach provides a general framework for modeling polygenic scores in family studies and allows for various model extensions that can be used to answer old questions about familial influences in new ways.