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：
10356016
负责人：
ROHAN Hugh Craig PALMER
金额：
$ 35.2万
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 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10356016
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.

项目摘要酒精和烟草使用和依赖的遗传风险因素的发现主要集中在个体遗传标记的贡献，例如单核苷酸多态性（SNP）。虽然这种方法已在绘制具有孟德尔遗传模式的罕见疾病的遗传倾向方面发挥了作用，这种方法在治疗具有多基因结构的复杂疾病方面取得的成功有限。这确定一组遗传因素，这些因素解释了使用和滥用责任的个体差异酒精和烟草/尼古丁将是了解未受控制的使用机制的重要一步。此外，开发新资源来预测或推断有问题使用酒精和烟草的风险基于遗传因素，这些因素在很大程度上解释了酒精和烟草使用/问题的个体差异与其他行为或神经认知表型一样，将是将研究发现转化为重要的一步预防策略。当前的提案解决了酒精和酒精的预测能力有限的问题通过提出使用综合方法和现有方法的新颖研究来进行烟草/尼古丁遗传学研究数据和生物信息学资源：（1）定位包含附加遗传效应的遗传变异酒精和烟草的使用和依赖，以及 (2) 开发一种新颖且免费的资源，增强了现有基因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建了分子遗传学、计算和统计学的多学科团队遗传学家来执行这些项目目标。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Associations of cigarette smoking with gray and white matter in the UK Biobank.

英国生物银行中吸烟与灰质和白质的关联。

DOI：
发表时间：
2020
期刊：
影响因子：
0
作者：
Gray, Joshua C;Thompson, Matthew;Bachman, Chelsie;Owens, Max M;Murphy, Mikela;Palmer, Rohan
通讯作者：
Palmer, Rohan

Multifactorial prediction of depression diagnosis and symptom dimensions.

抑郁症诊断和症状维度的多因素预测。

DOI：
发表时间：
2021-04
期刊：
影响因子：
11.3
作者：
McNamara, Mary E;Shumake, Jason;Stewart, Rochelle A;Labrada, Jocelyn;Alario, Alexandra;Allen, John J B;Palmer, Rohan;Schnyer, David M;McGeary, John E;Beevers, Christopher G
通讯作者：
Beevers, Christopher G

The intermediary role of adolescent temperamental and behavioral traits on the prospective associations between polygenic risk and cannabis use among young adults of European Ancestry.

青少年气质和行为特征对欧洲血统年轻人多基因风险与大麻使用之间的前瞻性关联的中介作用。

DOI：
发表时间：
2021
期刊：
影响因子：
0
作者：
Brick, Leslie A;Benca;Bertin, Lauren;Martin, Kathleen P;Risner, Victoria;Palmer, Rohan H C
通讯作者：
Palmer, Rohan H C

Associating broad and clinically defined polygenic scores for depression with depression-related phenotypes.

将广泛且临床定义的抑郁症多基因评分与抑郁症相关表型相关联。

DOI：
发表时间：
2023-04-21
期刊：
影响因子：
4.6
作者：
McGeary, John E;Benca;Risner, Victoria A;Beevers, Christopher G;Gibb, Brandon E;Palmer, Rohan H C
通讯作者：
Palmer, Rohan H C