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: 10369024
• 负责人: Sarah E Bergen
• 金额: $ 29.54万
• 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 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10369024
• 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; 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.

抽象的 在这项研究中，我们试图了解环境因素如何影响发展风险 精神分裂症 (SZ) 和双相情感障碍 (BD) 以及这些危险因素如何与这些疾病的遗传风险相互作用 失调。 SZ 和 BD 由于其深刻的个人和社会影响而具有重大的公共卫生重要性 成本。在理解遗传结构和特定位点方面取得了重大进展 单独或共同带来这些疾病的风险。虽然环境方面的研究结果可靠且可重复 SZ 的风险因素已经确定，但 BD 的风险因素却未能实现。我们打算向 通过对深圳和BD的环境风险进行并行调查来解决这种不平衡，并探索 与这些疾病的遗传风险可能存在相互作用。 对于这项工作，我们将利用瑞典国家登记册中的数据，其中包含整个国家的数据 瑞典人口的寿命（>1000 万）。我们的首要目标是评估环境影响 影响 SZ 或 BD 发展的风险因素以及这些因素是否相同或不同。这些将包括： 城市生活、感染、产科并发症、移民、童年逆境、大麻使用以及冬季或 春天出生。 此外，个体的基因可能会不同地影响对环境暴露的敏感性。 因此，我们将使用间接（家族史）和直接（分子遗传学）遗传评估 SZ 和 BD 与环境暴露相关的风险。本研究可用的注册信息是 准确、完整地向三级亲属提供其家族史的总人口测量数据 疾病（目标 2）。瑞典收集的 10,059 例 SZ 病例、11,052 例 BD 病例的现有分子遗传学数据 病例，22,138 个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 将能够直接比较环境暴露的行为 独立地并结合遗传风险来形成这些诊断。阐明机制 引起这些相关状况的因素可能会揭示预防和治疗的机会 最终减少这些破坏性疾病给个人和社会带来的负担的目标。