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

项目总结/摘要 后代在几乎每一个被调查的特征上都与他们的父母相似， 相似性已被证明具有挑战性。传统的遗传信息方法，如收养和 扩展的双胞胎家庭设计，已被证明是有价值的，有助于解开遗传和环境 父母-后代相似性的原因，但他们的结果的有效性依赖于对父母-后代相似性的强有力的假设。 亲属之间的协方差的原因，他们需要的数据是难以获得的，通常 专有的。在这里，我们介绍了一种遗传信息设计，SEMPGS，它使用多基因评分， 估计由于垂直传播（VT）而引起的后代性状的总变化，这种情况发生在 父母特质通过子女的养育环境直接影响子女的特质。VT的估计值 是基于可观察的遗传数据，并不依赖于对相对遗传的原因的强有力的假设。 协方差SEMPGS可以利用现有的公开可用的生物库和队列数据，大大扩展了 一系列的数据来源可用于回答有关亲子相似性的问题。 在这里，我们建议扩展和完善SEMPGS方法的方式，使其结果更准确 这可以为父母对后代的影响提供新的见解。这些发展包括测试 并解释了间接交配的机制，测试VT是否因性别而异， 父母和/或后代，设计多变量模型，评估父母的性状是否影响不同的 后代特征，并开发测试哪些特定的父母行为是基础的方法 观察VT。我们将在三个总计约61.5K的大型数据集中使用现有和拟议的SEMPGS模型 三人组、62 K亲子二人组、~ 39 K同胞组和~ 141 K配偶组，探讨VT对子代的作用 心理健康我们的研究将阐明亲本性状影响遗传病症状的机制。 抑郁症和注意力缺陷的后代，他们也将阐明的后果，父母 抑郁症对他们后代的身心健康造成的影响。此外，通过研究 我们的研究将有助于澄清多个配偶之间的配偶相似性的原因， 性状到项目结束时，我们预计将有工具为研究人员提供一种新的方法来解开 亲子相似性的原因，以便更清楚地了解亲子相似性的原因和后果 精神障碍和其他复杂的特征。

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.