Integrative Prioritization of Alcohol and Drug-Addiction Related Genetic Loci

酒精和毒瘾相关基因位点的综合优先排序

基本信息

批准号：
10092136
负责人：
ROHAN Hugh Craig PALMER
金额：
$ 36.59万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10092136
关键词：
Address Alcohol abuse Alcohol consumption Alcohol dependence Alcohols Architecture Archives Attention deficit hyperactivity disorder Bayesian Method Behavioral Biological Candidate Disease Gene Chromosome Mapping Colorado Communities Complex Data Data Discovery Data Set Databases Dependence Development Disease Drug Addiction Elements European Family Finland Genes Genetic Genetic Markers Genetic Polymorphism Genetic Risk Genetic study Genomics Genotype Genotype-Tissue Expression Project Goals Heritability Iceland Individual Individual Differences Inheritance Patterns Link Measures Methods Modeling Molecular Computations Molecular Genetics Neurocognitive Nicotine Northern Europe Pattern Persons Phenotype Physiological Population Predisposition Prevention strategy Proxy Psychopathology Rare Diseases Recording of previous events Research Resources Risk Sampling Scoring Method Severities Short-Term Memory Single Nucleotide Polymorphism Source Substance of Abuse Testing Texas Tissues Tobacco Tobacco Dependence Tobacco Use Disorder Tobacco use Translating Twin Multiple Birth Twin Studies United States National Institutes of Health Update Validation Variant alcohol misuse anti social base bioinformatics resource cohort comorbidity conduct problem data mining data resource database of Genotypes and Phenotypes endophenotype executive function externalizing behavior functional genomics gene expression database genetic risk factor genetic variant genome wide association study genome-wide genomic locus genomic platform in silico in vivo indexing innovation multidisciplinary new technology novel novel strategies population based psychosocial risk prediction simulation success tool trait whole genome

项目摘要

PROJECT ABSTRACT The discovery of genetic risk factors for alcohol and tobacco use and dependence has largely focused on the contribution of individual genetic markers, such as single nucleotide polymorphisms (SNPs). While this approach has been useful in mapping the genetic liability of rare diseases with a Mendelian pattern of inheritance, the approach has had limited success with complex diseases characterized by a more polygenetic architecture. The identification of a set of genetic factors that account for individual differences in the liability to use and misuse alcohol and tobacco/nicotine will be a major step in understanding mechanisms of undercontrolled use. Moreover, the development of novel resources to predict or infer risk for problematic use of alcohol and tobacco based on genetic factors that largely explain individual differences in alcohol and tobacco use/problems, as well as other behavioral or neurocognitive phenotypes, will be a major step in translating research discoveries into prevention strategies. The current proposal addresses the problem of limited predictive power in alcohol and tobacco/nicotine genetic studies by proposing novel research that uses an integrative approach and existing data and bioinformatics resources to: (1) localize genetic variants that comprise the additive genetic effects on alcohol and tobacco use and dependence, and (2) developing a novel and freely-available resource that enhances the way existing genetically informed samples are used for alcohol and tobacco risk prediction. The current application assembles a multidisciplinary team of molecular genetics and computational and statistical geneticists to execute these project aims.

项目摘要发现酒精和烟草使用和依赖性的遗传危险因素主要集中在单个遗传标记物的贡献，例如单核苷酸多态性（SNP）。而这种方法已经有助于绘制稀有疾病的遗传责任，以孟德尔的遗传模式，方法在以更多基因结构为特征的复杂疾病中取得了有限的成功。这识别一组遗传因素，这些因素解释了使用和滥用责任的个体差异酒精和烟草/尼古丁将是理解无法控制的使用机制的主要步骤。此外，开发新的资源来预测或推断出有问题使用酒精和烟草的风险基于遗传因素，在很大程度上解释了酒精和烟草使用/问题的个体差异作为其他行为或神经认知表型，将是将研究发现转化为预防策略。当前的提案解决了酒精预测能力有限的问题，烟草/尼古丁遗传研究通过提出使用综合方法和现有的新研究数据和生物信息学资源：（1）定位构成构成遗传影响的遗传变异酒精和烟草使用和依赖，以及（2）开发一种新颖且自由利用的资源增强现有遗传知识样本用于酒精和烟草风险预测的方式。这当前的应用程序组装了一个分子遗传学以及计算和统计的多学科团队遗传学家执行这些项目的目的。