The influence of multiple environmental exposures on suicide risk

项目简介：自杀是美国第十大死因，与国民经济 自杀造成的损失约为每年530亿美元。虽然自杀的原因很复杂，但自杀事件集中在 人们普遍假设，潜在的遗传易感性与家庭之间的相互作用 环境因素是导致自杀的原因之一。我们最近报告说自杀的风险很高 在盐湖所有自杀者中，短期接触细颗粒物和二氧化氮 2000年至2010年，犹他州县。调查天气和气候之间关系的补充研究 自杀研究发现，暴露在过热、太阳辐射和空气中会增加自杀风险。 到目前为止，研究主要集中在单一空气污染物或天气变量对自杀的影响。 因此，复杂的混合物，更真实地反映了一个人每天暴露在环境空气污染和 天气，还没有检查过关于自杀的情况。此外，潜在的特征是 影响一个人在暴露于空气污染物和天气变量后自杀的可能性 很大程度上不为人所知，但它们的认识对于制定有效的干预措施至关重要。世界银行的目标是 拟议的研究是为了1)彻底调查我们目前对个人的认识中的差距， 以及多种短期环境暴露(即环境空气污染物和天气)的综合影响 变量)关于自杀风险，2)确定人口统计、临床和家庭特征会增加 个人在短期暴露于周围空气污染和天气后自杀的易感性，以及3) 识别和表征与短期环境空气污染和天气相互作用的基因变异 增加自杀风险。我们在犹他大学处于独特的位置，可以开展拟议的工作。数据 我们的研究团队已获得的资源包括来自5,500个病例(Illumina)的分子数据 精神病学数据；665个病例的子集上有全基因组序列数据)。临床和人口学 相关信息可从犹他州验尸官办公室和犹他州人口数据库获得 (UPDB)。UPDB包括多代家谱记录、人口统计数据、生命记录数据、 关于犹他州早期生活状况的信息，以及约1100万人的当前医疗信息。我们 将使用在多次接触贝叶斯框架中分析的嵌套病例对照设计来量化影响 对多种环境暴露进行评估，并确定潜在的个人和家庭易感性。 基因与环境的相互作用将使用仅病例和病例交叉研究设计进行研究。学习 结果可能导致针对自杀的临床、教育和/或药物干预的发展， 针对高危人群。

Project Summary: Suicide is the 10th leading cause of death in the United States with the national economic costs of suicide approximated to be $53 billion annually. While suicide’s causes are complex, suicide clusters in families and it is widely hypothesized that interactions between an underlying genetic predisposition and environmental factors are in suicide’s causal pathway. We recently reported a heightened risk of suicide following short-term exposure to fine particulate matter and nitrogen dioxide among all suicides in Salt Lake County, Utah from 2000-2010. Complementary studies investigating the relationship between weather and suicide have found that suicide risk increases following exposure to excessive heat, solar radiation and draught. To date, studies have largely focused on the effects of single air pollutants or weather variables on suicide. Thus, complex mixtures, which more realistically reflect a person’s daily exposure to ambient air pollution and weather, have not been examined in regards to suicide. In addition, the underlying characteristics that influence a person’s vulnerability to suicide following exposure to air pollutants and weather variables are largely unknown yet their recognition is critical for developing effective interventions. The goals of the proposed study are to 1) investigate thoroughly the gaps in our current knowledge of the individual, additive and combined effects of multiple short-term environmental exposures (i.e. ambient air pollutants and weather variables) on suicide risk, 2) identify the demographic, clinical, and familial characteristics that increase a person’s susceptibility to suicide following short-term exposure to ambient air pollution and weather, and 3) identify and characterize genetic variants that interact with short-term ambient air pollution and weather to increase suicide risk. We are uniquely positioned at the University of Utah to carry out the proposed work. Data resources already available to our research team include molecular data from >5,500 cases (Illumina Psycharray data; whole genome sequence data is available on a subset of 665 cases). Clinical and demographic information is available from the Utah State Office of the Medical Examiner and the Utah Population Database (UPDB). The UPDB includes multi-generation genealogical records, demographic data, vital records data, information on early life conditions, and current medical information on ~11 million individuals in Utah. We will use a nested case-control design analyzed in a multi-exposure Bayesian framework to quantify the effects of multiple environmental exposures and identify underlying individual-level and familial susceptibilities. Gene-environment interactions will be investigated using case-only and case-crossover study designs. Study results may lead to the development of clinical, educational and/or pharmacological interventions for suicide, targeted at high-risk individuals.