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.
