A comparison of environmental and genetic risks for schizophrenia and bipolar disorder: A Swedish national study

精神分裂症和双相情感障碍的环境和遗传风险比较：瑞典国家研究

• 批准号: 10577897
• 负责人: Sarah E Bergen
• 金额: $ 28.37万
• 依托单位: KAROLINSKA INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-18 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10577897
• 关键词: Address; Affect; Age of Onset; Attention; Bipolar Disorder; Birth; Clinical; Data; Development; Diagnosis; Disease; Environmental Exposure; Environmental Impact; Environmental Risk Factor; Etiology; Family; Family history of; Foundations; Genes; Genetic; Genetic Risk; Genotype; Heritability; Individual; Infection; Inherited; Investigation; Longevity; Measures; Mental disorders; Molecular Genetics; Pathway interactions; Population; Prevention; Prevention strategy; Public Health; Recording of previous events; Registries; Reporting; Research; Resources; Risk; Risk Factors; Role; Sampling; Scandinavian; Schizophrenia; Shapes; Single Nucleotide Polymorphism; Sweden; Testing; Work; base; childhood adversity; comparative; disorder risk; genetic architecture; genetic risk assessment; genetic risk factor; indexing; informant; marijuana use; migration; novel; obstetrical complication; personal narratives; risk prediction; schizophrenia risk; severe psychiatric disorder; societal costs; therapeutic target

Abstract In this study we seek to understand how environmental factors influence the risk of developing schizophrenia (SZ) and bipolar disorder (BD) and how these risk factors interact with genetic risk for these disorders. SZ and BD are of major public health importance owing to their profound personal and societal costs. Major advances have been made in understanding the genetic architectures and specific loci conferring risk for these disorders individually and jointly. While robust, replicated findings for environmental risk factors for SZ have been identified, these have failed to materialize for BD. We intend to address to address this imbalance through parallel investigations of environmental risk for SZ and BD and explore possible interactions with genetic risk for these disorders. For this work, we will utilize data from the Swedish National Registers which contain data across the lifespan for the Swedish population (>10 million). Our first aim seeks to assess the impact of environmental risk factors on the development of SZ or BD and whether these are shared or divergent. These will include: urban living, infections, obstetric complications, migration, childhood adversity, cannabis use, and winter or spring birth. Additionally, an individual’s genes may differentially affect sensitivity to environmental exposures. Therefore, we will use both indirect (family history) and direct (molecular genetic) assessments of genetic risk for SZ and BD in relation to environmental exposures. Registry information available for this study is accurate and complete out to third degree relatives for total population measures of family history for these disorders (Aim 2). Existing molecular genetic data collected in Sweden for 10,059 SZ cases, 11,052 BD cases, and 22,138 controls will be used for analyses of directly measured genetic risk (Aim 3). Concurrent examination of BD and SZ will allow for direct comparisons of how environmental exposures act independently and in conjunction with genetic risk to shape these diagnoses. Elucidating the mechanisms which give rise to these related conditions may reveal opportunities for prevention efforts and therapeutic targets to ultimately reduce the personal and societal burdens of these devastating disorders.

摘要 在这项研究中，我们试图了解环境因素如何影响发展的风险， 精神分裂症（SZ）和双相情感障碍（BD）以及这些风险因素如何与这些风险的遗传风险相互作用 紊乱SZ和BD由于其深刻的个人和社会影响， 成本在理解遗传结构和特定位点方面取得了重大进展 从而单独地和共同地赋予这些疾病的风险。虽然对环境的研究结果是可靠的， 已经确定了SZ的风险因素，但这些风险因素未能在BD中实现。我们打算向 通过对深圳和屋宇署的环境风险进行平行调查，解决这种不平衡的问题，并探讨 可能与这些疾病的遗传风险相互作用。 在这项工作中，我们将利用瑞典国家登记册中的数据，这些数据包含整个 瑞典人口的平均寿命（> 1000万）。我们的第一个目标是评估环境影响 发展深圳或BD的风险因素，以及这些因素是共同的还是不同的。这些措施包括： 城市生活、感染、产科并发症、移徙、童年逆境、大麻使用以及冬季或 春天出生 此外，个体的基因可能会对环境暴露的敏感性产生不同的影响。 因此，我们将使用间接（家族史）和直接（分子遗传学）评估遗传学， SZ和BD与环境暴露有关的风险。本研究可用的登记信息为 准确和完整的三度亲属的总人口的家庭史措施，这些 疾病（目标2）。在瑞典收集的10，059例SZ病例和11，052例BD的现有分子遗传学数据 病例和22，138例对照将用于分析直接测量的遗传风险（目标3）。 同时检查BD和SZ将允许直接比较环境暴露如何起作用 独立地和结合遗传风险来形成这些诊断。阐明机制 引起这些相关疾病的可能揭示了预防工作和治疗的机会 目标是最终减轻这些毁灭性疾病的个人和社会负担。

项目成果

Impact of Early-Life Factors on Risk for Schizophrenia and Bipolar Disorder.

早期生活因素对精神分裂症和双相情感障碍风险的影响。

• DOI: 10.1093/schbul/sbac205
• 发表时间: 2023
• 期刊: Schizophrenia bulletin
• 影响因子: 6.6
• 作者: Robinson,Natassia;Ploner,Alexander;Leone,Marica;Lichtenstein,Paul;Kendler,KennethS;Bergen,SarahE
• 通讯作者: Bergen,SarahE

Environmental Risk Factors for Schizophrenia and Bipolar Disorder and Their Relationship to Genetic Risk: Current Knowledge and Future Directions.

• DOI: 10.3389/fgene.2021.686666
• 发表时间: 2021
• 期刊: Frontiers in genetics
• 影响因子: 3.7
• 作者: Robinson N;Bergen SE
• 通讯作者: Bergen SE

Migration and risk of schizophrenia and bipolar disorder: A Swedish national study.

移民与精神分裂症和双相情感障碍的风险：瑞典国家研究。

• DOI: 10.1016/j.schres.2023.08.022
• 发表时间: 2023
• 期刊: Schizophrenia research
• 影响因子: 4.5
• 作者: Robinson,Natassia;Ploner,Alexander;Müller-Eberstein,Roxana;Lichtenstein,Paul;Kendler,KennethS;Bergen,SarahE
• 通讯作者: Bergen,SarahE