Genetic analysis of high-risk Utah suicide pedigrees

犹他州高风险自杀家系的遗传分析

基本信息

批准号：
9033440
负责人：
Hilary Coon
金额：
$ 15.53万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9033440
关键词：
Accounting Age Biological Cause of Death Cessation of life Characteristics Collaborations Communities DNA Data Data Aggregation Data Set Databases Detection Dideoxy Chain Termination DNA Sequencing Discrimination Disease Environment Epidemiologic Studies Exhibits Family Fostering Future Gender Gene Expression Regulation Genealogy Genes Genetic Research Genetic Risk Genetic Variation Genome Genotype Hand Health Heritability Individual Knowledge Light Link Medical Medical Examiners Methods Molecular Pathway interactions Phenotype Population Population Database Promoter Regions Records Relative (related person)Resources Risk Risk Factors Sampling Source Suicide Suicide attempt Testing United States United States National Center for Health Statistics Utah Validation Variant World Health Organization accomplished suicide analytical method cohort computerized demographics exome exome sequencing follow-up genetic analysis genetic pedigree genetic risk factor genetic variant genome sequencing high risk interest male non-genetic population based psychogenetics public health relevance rare variant suicidal morbidity suicidal risk suicide rate tool

项目摘要

DESCRIPTION (provided by applicant): Suicide is a significant health concern. There are over 33,000 suicide deaths per year in the United States, accounting for 1.3% of all fatalities (WISQARS, 2005), and about 2% of deaths worldwide (World Health Organization, 2000). Aggregated data across multiple large studies has produced heritability estimates of completed suicide of 45%. The Rocky Mountain States have much higher age-adjusted suicide rates, and Utah is consistently in the top ten. In Utah, suicide is the leading cause of death for males between the ages of 15 and 54. Our project will use a large DNA resource already collected from decedents through a long-term collaboration with the centralized Utah State Office of the Medical Examiner (OME). Records of >2,000 decedents with DNA were linked to the Utah Population DataBase (UPDB), a computerized genealogy database that includes medical data, demographic information, and genealogical data for over 6.5 million individuals. Using the UPDB, we identified 27 high risk families containing ~150 suicide decedents with DNA. As a rare condition (1-2/10,000 per year), aggregation of suicide completion in high-risk pedigrees represents a unique resource to study risk factors. We will use the genealogical, demographic, and medical data in the UPDB to identify and focus on the most compelling of these high-risk suicide pedigrees; those that contain both a significant excess of suicide completion and that exhibit the most discriminating characteristics compared to non-familial suicide. By using these phenotypic comparisons to choose the most unique high-risk pedigrees, we will increase homogeneity and strengthen our ability to isolate genetic variants related to suicide risk. These discriminating phenotypes will also identify non-genetic factors associated with high familial risk that can foster other epidemiological studies, and can facilitate future gene x environment analyses. We currently have in hand a large resource of DNA and phenotype information from ~2500 additional Utah suicide decedents. This sample will grow to over 4000 DNAs by the end of the study, the largest population-based sample of DNA from suicide decedents ever collected. We propose to focus on unusual high-risk suicide pedigrees with increased likelihood for more penetrant rare genetic variation, followed by confirmation and follow-up analyses in large cohorts of Utah decedents and publicly-available psychiatric data sets. The detection of genetic variants associated with suicide could shed light on biological pathways leading to suicide risk in the population, or in association with specific disorders. We have chosen state-of-the-art analytical methods, and have assembled a team of experts (analytic, phenotypic, and molecular) to explore these unique data resources to identify genetic risk factors for suicide. The detection of rare variants associated with suicide could shed light on biological pathways leading to suicide risk in the population, or in association with specific disorders.

描述（由申请人提供）：自杀是一个重大的健康问题。美国每年有超过 33,000 人自杀死亡，占所有死亡人数的 1.3%（WISQARS，2005 年），约占全世界死亡人数的 2%（世界卫生组织，2000 年）。多项大型研究的汇总数据得出自杀完成率的遗传性估计为 45%。落基山脉各州的年龄调整自杀率要高得多，而犹他州一直位居前十。在犹他州，自杀是 15 岁至 54 岁男性死亡的主要原因。我们的项目将使用通过与犹他州集中体检办公室 (OME) 长期合作从死者那里收集的大量 DNA 资源。）。超过 2,000 名带有 DNA 的死者记录与犹他州人口数据库 (UPDB) 相关联，这是一个计算机化的家谱数据库，其中包括超过 650 万人的医疗数据、人口统计信息和家谱数据。使用 UPDB，我们确定了 27 个高风险家庭，其中包含约 150 名带有 DNA 的自杀死者。作为一种罕见的情况（每年 1-2/10,000 例），高风险谱系中自杀完成情况的汇总代表了研究风险因素的独特资源。我们将使用 UPDB 中的家谱、人口统计和医学数据来识别并关注这些高风险自杀谱系中最引人注目的一个；与非家庭自杀相比，那些自杀完成率显着过高且表现出最具区别性特征的自杀者。通过使用这些表型比较来选择最独特的高风险谱系，我们将增加同质性并增强我们分离与自杀风险相关的遗传变异的能力。这些区分表型还将识别与高家族风险相关的非遗传因素这可以促进其他流行病学研究，并可以促进未来的基因 x 环境分析。目前，我们手头有来自约 2500 名犹他州自杀死者的大量 DNA 和表型信息。到研究结束时，该样本将增加到超过 4000 个 DNA，这是迄今为止从自杀者死者中收集的最大的基于人群的 DNA 样本。我们建议重点关注不寻常的高风险自杀谱系，这些谱系出现更具渗透性的罕见遗传变异的可能性更大，然后对犹他州死者的大型队列和公开的精神病学数据集进行确认和后续分析。检测与自杀相关的遗传变异可以揭示导致人群自杀风险或与特定疾病相关的生物学途径。我们选择了最先进的分析方法，并组建了一个专家团队（分析、表型和分子）来探索这些独特的数据资源，以确定自杀的遗传风险因素。这检测与自杀相关的罕见变异可以揭示导致人群自杀风险或与特定疾病相关的生物学途径。