Causes and consequences of mental disorders: The environmental and genetic influences of parents on offspring.

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PROJECT SUMMARY/ABSTRACT Offspring resemble their parents on nearly every trait investigated but understanding the causes of this similarity has proven challenging. Traditional genetically informative approaches, such as adoption and extended twin family designs, have proven valuable in helping to disentangle the genetic and environmental causes for parents-offspring similarity, but the validity of their results rest upon strong assumptions about the reasons for covariance among relatives and they require data that is difficult to obtain and typically proprietary. Here, we introduce a genetically informative design, SEMPGS, that uses polygenic scores to estimate the total variation in offspring traits that is due to vertical transmission (VT), which occurs when a parental trait directly influences an offspring trait via the offspring’s rearing environment. This estimate of VT is based on observable genetic data and does not depend on strong assumptions about the causes of relative covariances. SEMPGS can utilize existing publicly available biobank and cohort data, greatly expanding the range of data sources available to answer questions about parent-offspring resemblance. Here, we propose to extend and refine the SEMPGS approach in ways that will make its results more accurate and that can provide novel insights into parental influences on offspring. These developments include testing and accounting for mechanisms of assortative mating, testing whether VT differs depending on the sex of the parent and/or offspring, designing multivariate models that assess whether a parental trait influences different offspring trait(s), and developing approaches for testing which specific parental behaviors underlie observations of VT. We will use existing and proposed SEMPGS models in three large datasets totaling ~61.5K trios, 62K parent-offspring duos, ~39K siblings and ~141K spousal pairs to explore the role of VT on offspring mental health. Our studies will elucidate the mechanisms by which parental traits influence symptoms of depression and attentional deficits in offspring, and they will also elucidate the consequences that parental depression has on their offspring’s physical and mental well-being. Moreover, by investigating the correlations of polygenic scores across spouses, our studies will help clarify the causes of spousal similarity across multiple traits. By project’s end, we anticipate having tools that provide researchers with a new way to disentangle the causes of parent-offspring resemblance, allowing for a clearer understanding of the causes and consequences of mental disorders and other complex traits.