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

精神障碍的原因和后果：父母对后代的环境和遗传影响。

• 批准号: 10665036
• 负责人: Matthew Charles Keller
• 金额: $ 73.46万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10665036
• 关键词: Accounting; Adoption; Age; Alcohol consumption; Anxiety; Attention; Attentional deficit; Behavior; Child; Cognition; Complex; Data; Data Set; Data Sources; Development; Environment; Equation; Explosion; Family; Fertilization; Functional disorder; Genes; Genetic; Health; Human Resources; Literature; Measures; Mediation; Mental Depression; Mental Health; Mental disorders; Modeling; Nature; Parents; Partner in relationship; Personal Satisfaction; Phenotype; Play; Psychopathology; Reproducibility; Research Personnel; Rest; Risk; Role; Sampling; Shapes; Siblings; Smoking; Spouses; Symptoms; Techniques; Testing; Time; Twin Multiple Birth; Underrepresented Populations; Variant; Vertical Transmission; Well in self; biobank; cohort; depressive symptoms; design; ethnic diversity; improved; insight; large datasets; novel; offspring; parental influence; parental role; pleiotropism; sex; social; tool; trait; whole genome

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.

项目摘要/摘要 后代几乎在调查的每个特征上都类似于父母，但了解这一点的原因 相似性已被证明是挑战。传统的遗传信息丰富的方法，例如采用和 扩展的双胞胎家庭设计已被证明在帮助解散遗传和环境方面有价值 父母的原因相似性的原因，但结果的有效性取决于对 亲戚之间协方差的原因，它们需要难以获得的数据，通常 所有权。在这里，我们介绍了一种一般有用的设计，即SEMPG，该设计使用多基因分数 估计垂直传播（VT）引起的后代特征的总变化，该特征发生在 父母的特质直接通过后代的饲养环境影响后代特质。 VT的估计值 基于可观察的遗传数据，不依赖于相对原因的强烈假设 协方差。 SEMPG可以利用现有的现有公开可用的生物库和队列数据，从而大大扩展 数据源范围可用于回答有关父母的相似性问题。 在这里，我们建议以使其结果更准确的方式扩展和完善SEMPG方法 这可以为父母对后代的影响提​​供新颖的见解。这些发展包括测试 并考虑分类交配机制，测试VT是否取决于性别 父母和/或后代，设计多元模型，以评估父母特质是否影响不同 后代特征，以及开发测试哪些特定父母行为的方法 VT的观察。我们将在总计约61.5k的三个大数据集中使用现有和拟议的SEMPGS模型 Trios，62k父母源二重奏，〜39k兄弟姐妹和〜141K配偶对探索VT在后代的作用 心理健康。我们的研究将阐明父母特征影响的机制 后代的抑郁和注意力缺陷，它们还将阐明父母的后果 抑郁症的身心健康。而且，通过研究相关性 在跨配偶的多基因分数中，我们的研究将有助于阐明多个配偶相似性的原因 特质。到项目的结尾，我们预计拥有工具，为研究人员提供一种新的方法来解开 父母源相似的原因，可以更清楚地了解 精神障碍和其他复杂特征。

项目成果

Intergenerational effects of parental educational attainment on parenting and childhood educational outcomes: Evidence from MoBa using within-family Mendelian randomization.

父母受教育程度对养育和儿童教育成果的代际影响：来自 MoBa 使用家庭内孟德尔随机化的证据。

• DOI: 10.1101/2023.02.22.23285699
• 发表时间: 2023
• 期刊: medRxiv : the preprint server for health sciences
• 作者: Havdahl,Alexandra;Hughes,AmandaM;Sanderson,Eleanor;Ask,Helga;Cheesman,Rosa;Reichborn-Kjennerud,Ted;Andreassen,OleA;Corfield,ElizabethC;Hannigan,Laurie;Magnus,Per;Njølstad,PålR;Stoltenberg,Camilla;Torvik,FarteinAsk;Brandlistu
• 通讯作者: Brandlistu