The influence of multiple environmental exposures on suicide risk

项目摘要：自杀是美国第十大死亡原因， 每年自杀造成的损失约为530亿美元。虽然自杀的原因很复杂，但自杀集中在 它是广泛假设，一个潜在的遗传易感性之间的相互作用， 环境因素在自杀的因果路径中。我们最近报道了自杀风险的增加 在盐湖的所有自杀者中， 2000-2010年犹他州县。补充研究调查天气和气候变化之间的关系， 自杀研究发现，暴露在过热、太阳辐射和通风条件下，自杀风险会增加。 迄今为止，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上。 因此，复杂的混合物，更真实地反映了一个人每天暴露于环境空气污染， 天气，还没有被调查是否自杀。此外， 影响一个人在暴露于空气污染物和天气变量后自杀的脆弱性， 这些问题在很大程度上不为人知，但认识到这些问题对于制定有效的干预措施至关重要。的目标 建议的研究是：1）彻底调查我们目前对个体，添加剂 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）对自杀风险的影响，2）确定增加自杀风险的人口统计学，临床和家族特征， 人在短期暴露于环境空气污染和天气后自杀的可能性，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遗传变异， 增加自杀风险。我们在犹他州大学的独特地位，以开展拟议的工作。数据 我们的研究团队已经可以利用的资源包括来自> 5，500个病例的分子数据（Illumina Psycharray数据;全基因组序列数据可在665个病例的子集上获得）。临床和人口统计学 信息可从犹他州州医学检查办公室和犹他州人口数据库获得 （B）.该数据库包括多代家谱记录、人口统计数据、生命记录数据， 关于早期生活状况的信息，以及犹他州约1100万人的当前医疗信息。我们 将使用嵌套病例对照设计，在多次暴露贝叶斯框架中分析，以量化影响 多种环境暴露的影响，并确定潜在的个人水平和家庭易感性。 将使用仅病例和病例交叉研究设计研究基因-环境相互作用。研究 结果可能导致自杀的临床，教育和/或药理干预的发展， 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.