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

摘要 在这项研究中，我们试图了解环境因素是如何影响发病风险的。 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遗传风险相互作用 精神错乱。SZ和BD具有重大的公共卫生重要性，因为它们具有深刻的个人和社会意义 成本。在了解遗传结构和特定基因座方面取得了重大进展 单独和联合地赋予这些疾病的风险。虽然有可靠的、重复的环境研究结果 SZ的风险因素已经确定，但BD的风险因素未能实现。我们打算寄给 通过平行调查深圳和BD的环境风险来解决这种不平衡问题，并探索 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处的数据，其中包含 瑞典人口的寿命(1000万英镑)。我们的首要目标是评估环境的影响 SZ或BD发生的危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、移民、童年逆境、大麻使用和冬季或 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，我们将同时使用间接(家族史)和直接(分子遗传学)基因评估 SZ和BD与环境暴露相关的风险。可用于本研究的注册信息为 准确、完整地给出三级亲属的总人口和家族史的衡量标准 障碍(目标2)。瑞典收集的10,059例SZ病例，11,052例BD的现有分子遗传学数据 将使用22,138个对照来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的作用 独立地并结合遗传风险来形成这些诊断。阐明其作用机制 导致这些相关疾病的疾病可能会揭示出预防和治疗的机会 目标是最终减少这些破坏性疾病造成的个人和社会负担。

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.