Genetic Dissection in Pedigrees of Substance Use and Mood Disorders Comorbidity

药物使用和情绪障碍合并症谱系的基因剖析

基本信息

  • 批准号:
    9062049
  • 负责人:
  • 金额:
    $ 10.44万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-07-15 至 2017-06-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): This project aims to identify genetic variants that contribute to the comorbidity of substance use disorders (SUD) and mood disorders (MD). Each of these disorders represents among the greatest disease burdens worldwide. Yet their frequent co-morbidity is itself a major public health problem: individuals in whom SUD and MD co-occur have clinical outcomes that are dramatically worse than those of individuals who suffer from only one of these conditions. Our limited understanding of the factors that generate SUD/MD co-morbidity hinders our ability to prevent it or to successfully treat affected individuals. In particular, although both types of disorder are highly heritable, it remains unclear whether the set of genetic variants influencing risk for SUD overlaps with the genetic variants contributing to risk for MD, or even whether there are variants that specifically predispose to SUD/MD co-morbidity. To elucidate the genetic basis of SUD/MD comorbidity this project will analyze comprehensive genetic variation data obtained through whole genome sequencing (WGS) of members of 26 pedigrees from the genetically related population isolates of Antioquia, Colombia (CO) and the Central Valley of Costa Rica (CR). The project will leverage the infrastructure and data (extensive phenotypes, high-resolution genome-wide genotypes, and deep WGS) from an existing study of 800 individuals in these pedigrees that has focused on identifying genetic variants contributing to severe bipolar disorder (BP-I) and has already genetically mapped loci for both BP-I and for BP-I endophenotypes. The majority of BP-I individuals worldwide demonstrate comorbidity with one or more SUD, and preliminary data indicate that these pedigrees include a substantial number of members comorbid for SUD with either BP-I or another form of MD. To conduct genetic investigations of SUD/MD comorbidity this project will: 1) Recruit 300 additional 1st degree relatives of existing subjects, targeting individuals affected with SUD and a broad spectrum of MD, achieving a total sample of 1100 individuals; 2) Conduct phenotypic assessments in the 1100-person sample to quantify substance use, diagnose SUD, and identify heritable endophenotypes for SUD and SUD/MD comorbidity; 3) Perform additional genotyping and WGS to achieve comprehensive genetic variation data for the entire 1100-person sample; 4) Carry out genetic mapping studies to identify variants contributing to SUD, SUD/MD comorbidity, and to SUD-related endophenotypes. Future studies will follow-up our results in a variety of independent study samples from CO, CR and the U.S.
 描述(由申请人提供):该项目旨在确定导致物质使用障碍(SUD)和情绪障碍(MD)共病的遗传变异。这些疾病中的每一种都是全世界最大的疾病负担。然而,他们频繁的共同发病本身就是一个重大的公共卫生问题:SUD和MD共同发生的个体的临床结果比仅患有其中一种疾病的个体的临床结果要差得多。我们对产生SUD/MD共病的因素的有限理解阻碍了我们预防或成功治疗受影响个体的能力。特别是,尽管这两种类型的疾病都是高度遗传的,但目前尚不清楚影响SUD风险的遗传变异是否与导致SUD的遗传变异重叠。 MD的风险,甚至是否存在特别易患SUD/MD共病的变异。为了阐明SUD/MD共病的遗传基础,该项目将分析通过全基因组测序(WGS)从安蒂奥基亚、哥伦比亚(CO)和哥斯达黎加(CR)的中央谷的遗传相关群体分离物中获得的26个家系成员的综合遗传变异数据。该项目将利用这些家系中800名个体的现有研究的基础设施和数据(广泛的表型,高分辨率全基因组基因型和深度WGS),该研究专注于识别导致严重双相情感障碍(BP-I)的遗传变异,并且已经为BP-I和BP-I内表型绘制了基因座。世界范围内大多数BP-I个体表现出与一种或多种SUD的共病,初步数据表明,这些家系包括大量与BP-I或另一种形式的MD共病的SUD成员。为了进行SUD/MD共患病的遗传学调查,该项目将:1)招募300名现有受试者的额外一级亲属,针对受影响的个人 2)在1100人样本中进行表型评估以量化物质使用、诊断SUD并鉴定SUD和SUD/MD共病的可遗传内表型; 3)进行额外的基因分型和WGS以获得整个1100人样本的全面遗传变异数据; 4)进行遗传作图研究以鉴定促成SUD、SUD/MD共病和SUD相关内表型的变体。未来的研究将跟踪我们在CO、CR和美国的各种独立研究样本中的结果。

项目成果

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NELSON B. FREIMER其他文献

NELSON B. FREIMER的其他文献

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{{ truncateString('NELSON B. FREIMER', 18)}}的其他基金

A Latin American biobank for large-scale genetics research on severe mental illness
拉丁美洲生物库,用于严重精神疾病的大规模遗传学研究
  • 批准号:
    10386289
  • 财政年份:
    2021
  • 资助金额:
    $ 10.44万
  • 项目类别:
4/4 Powering Genetic Discovery for Severe Mental Illness in Latin American and African Ancestries
4/4 推动拉丁美洲和非洲血统中严重精神疾病的基因发现
  • 批准号:
    10263326
  • 财政年份:
    2020
  • 资助金额:
    $ 10.44万
  • 项目类别:
A Latin American biobank for large-scale genetics research on severe mental illness
拉丁美洲生物库,用于严重精神疾病的大规模遗传学研究
  • 批准号:
    10363749
  • 财政年份:
    2020
  • 资助金额:
    $ 10.44万
  • 项目类别:
4/4 Powering Genetic Discovery for Severe Mental Illness in Latin American and African Ancestries
4/4 推动拉丁美洲和非洲血统中严重精神疾病的基因发现
  • 批准号:
    10478253
  • 财政年份:
    2020
  • 资助金额:
    $ 10.44万
  • 项目类别:
4/4 Powering Genetic Discovery for Severe Mental Illness in Latin American and African Ancestries
4/4 推动拉丁美洲和非洲血统中严重精神疾病的基因发现
  • 批准号:
    10383005
  • 财政年份:
    2020
  • 资助金额:
    $ 10.44万
  • 项目类别:
1/2 Genomic Strategies to Identify High-impact Psychiatric Risk Variants
1/2 识别高影响精神病风险变异的基因组策略
  • 批准号:
    8806391
  • 财政年份:
    2014
  • 资助金额:
    $ 10.44万
  • 项目类别:
Genome Sequencing in Extended Bipolar Pedigrees
扩展双相谱系的基因组测序
  • 批准号:
    8474847
  • 财政年份:
    2012
  • 资助金额:
    $ 10.44万
  • 项目类别:
Genome Sequencing in Extended Bipolar Pedigrees
扩展双相谱系的基因组测序
  • 批准号:
    8321412
  • 财政年份:
    2012
  • 资助金额:
    $ 10.44万
  • 项目类别:
Genomic and Metabolomic Profiling of Finnish Familial Dyslipidemia Families
芬兰家族性血脂异常家族的基因组和代谢组学分析
  • 批准号:
    8485662
  • 财政年份:
    2012
  • 资助金额:
    $ 10.44万
  • 项目类别:
Genomic and Metabolomic Profiling of Finnish Familial Dyslipidemia Families
芬兰家族性血脂异常家族的基因组和代谢组学分析
  • 批准号:
    8644877
  • 财政年份:
    2012
  • 资助金额:
    $ 10.44万
  • 项目类别:
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