Investigating the molecular mechanisms and consequences of assortative mating in major psychiatric disorders: completing a missing piece of the psychiatric genetics puzzle

项目总结 最近的研究表明，被诊断出患有严重精神障碍的人比 健康的人选择有自己或其他精神疾病的配偶。这是什么角色？ 然而，非随机交配可能在精神疾病的传播中发挥作用，目前尚不清楚。哪里 父母是一种疾病的同型(例如，父母都有精神分裂症的诊断)，子女会 从每个父母那里收到与这种疾病相关的基因变异--把他们放在特别高的位置 这种疾病发展的遗传风险。然而，这种类型的复合遗传风险也可能发生在 异型配对(例如，父母一方患有精神分裂症，另一方患有躁郁症)， 各种疾病都有遗传风险。先前的研究表明，这种异型配对在 精神病患者，了解这些后代的风险程度是一种 很重要的问题。 因此，这项建议的主要目标是利用瑞典可用数据的独特规模 在儿童的后代中确定重大精神疾病诊断风险变化的医疗登记册 父母在重大精神疾病诊断中是同型或异型的，相对于子代的风险 受影响的或健康的单亲父母。有八种主要精神疾病之一的父母-注意力缺陷 多动症、躁郁症、广泛性焦虑症、抑郁症、强迫症- 强迫症、精神分裂症、社交恐惧症和药物滥用--将在这项工作中被考虑， 这些疾病在他们的后代中的发生率与匹配的人群对照中的发生率相比。 除了描述这些风险之外，本项目还建议检查风险变量的重叠程度 一种特殊的疾病-精神分裂症-在被诊断患有这种疾病的子女的父母中。如果 发现，这种类型的分子关联将发出一个明确的机制，通过这种机制可能会在 同型或异型配对的后代，虽然它的缺失可能表明环境在 塑造这些额外的风险。

PROJECT SUMMARY Recent research has indicated that individuals diagnosed with a major psychiatric disorder are more likely than healthy individuals to select a mate with their own or an alternative psychiatric condition. What role this nonrandom mating may play in the transmission of psychiatric illness, however, remains unclear. Where parents are homotypic for a disorder (e.g., both parents have a diagnosis of schizophrenia), offspring will receive genetic variants from each parent that are related to that disorder – placing them at particularly high genetic risk for that condition's development. However, this type of compounded genetic risk may also occur in heterotypic pairings (e.g., one parent having schizophrenia, the other bipolar disorder), as many psychiatric conditions share genetic risks. With prior research suggesting that such heterotypic pairings are pervasive in psychiatric populations, understanding the degree to which risks are sustained in these offspring is an important question. The primary goal of this proposal is, therefore, to leverage the unique scale of data available in the Swedish Medical Registers to determine the change in risk for major psychiatric diagnoses, among the offspring of parents who are homotypic or heterotypic for major psychiatric diagnoses, relative to the risk in offspring of single affected or healthy parents. Parents with any of eight major psychiatric diagnoses - attention deficit hyperactivity disorder, bipolar disorder, generalized anxiety disorder, major depressive disorder, obsessive- compulsive disorder, schizophrenia, social phobia, and substance abuse – will be considered in this work, with the incidence of these conditions in their offspring compared to the incidence in matched population controls. In addition to describing these risks, this project also proposes to examine the degree of overlap in risk variants for a particular condition – schizophrenia – among the parents of offspring diagnosed with this condition. If found, this type of molecular correlation would signal a clear mechanism by which a disorder may arise in offspring of homo- or heterotypic pairs, while its absence could suggest a stronger role for environment in shaping these added risks.