Sex-specific analysis of opioid dependence GWAS and beyond

阿片类药物依赖 GWAS 及其他的性别特异性分析

基本信息

批准号：
9432193
负责人：
JOEL GELERNTER
金额：
$ 8.51万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-08-05 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9432193
关键词：
Abstinence Address Administrative Supplement Affect African African American Alcoholism Alcohols American Animals Basic Science Binding Biological Biological Assay Biology Brain Budgets Candidate Disease Gene Cannabis Clinical Cocaine Collaborations Collection Comorbidity Computer software DISC1 gene Data Databases Dependence Diagnostic Dose Drug Addiction Electrophoretic Mobility Shift Assay European Exons Family Female Follow-Up Studies Gender Gene Expression Gene Expression Regulation Genes Genetic Genetic Risk Genomic Segment Genotype Goals Heritability Human In Vitro Individual Manuscripts Medical Meta-Analysis Methods Modeling Nicotine Opiate Addiction Opioid Parents Phase Phenotype Population Preparation Prevention strategy Procedures Publishing Quantitative Trait Loci Regulatory Element Relapse Reporting Research Research Personnel Resources Risk Sampling Self Administration Severity of illness Sex Characteristics Signal Transduction Strategic Planning Structure Testing Therapeutic Tissues Treatment outcome United States National Institutes of Health Untranslated RNA Variant Withdrawal Woman Women&apos s Health Work Yang addiction case control cohort cost cost effective deep sequencing density design drug of abuse exome exome sequencing experience follow-up genetic risk assessment genetic risk factor genetic variant genome analysis genome wide association study genomic data girls individualized prevention instrument male men methadone maintenance pleiotropism programs promoter rare variant risk variant segregation sex social targeted sequencing tool trait treatment program treatment response treatment strategy

项目摘要

Sex differences exist in multiple phases of opioid dependence (OD) including acquisition, escalation, addiction, withdrawal, relapse, and treatment response. Overall, men are more likely to become OD than women, although women tend to progress and develop medical or social consequences faster, have more difficulty discontinuing use, and more vulnerable to relapse. Thus, determining sex-specific factors underlying OD is critical for optimizing prevention and treatment strategies for men and women with OD. Identifying relevant genetic factors holds particular promise. Although studies have reported sex-specific heritability of OD and different association results for men and women for some candidate genes in OD, the results to date are meagre, and sex-specific genome wide association studies (GWAS) on OD have never been reported. We will use rigorous statistical approaches to identify sex-specific genetic risk factors for OD. We have a well-characterized substance-dependent (SD) cohort for African and European Americans with GWAS and exome-array data that can be analyzed and leveraged with publically available genetic and genomics data. This large SD cohort has been assessed using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) instrument. In this proposal, OD defined by DSM criterion count will be the targeted trait for analysis. The overall goal of this administrative supplement proposal is to analyze the genetic data we have collected for women and men to identify most effectively sex-specific genetic variants.

性别差异存在于阿片类药物依赖性（OD）的多个阶段，包括获取，升级，成瘾，戒断，复发和治疗反应。总体而言，男人更有可能比女性成为OD，尽管女性倾向于进步并发展医疗或社会后果更快，停止使用更加困难，并且更容易发生复发。因此，确定OD的性别特定因素对于优化预防和患有OD的男性和女性的治疗策略。识别相关的遗传因素的存在特别的承诺。尽管研究报告了特定的性别遗传力和不同的性别遗传力 OD中某些候选基因的男性和女性的关联结果，迄今为止的结果为微薄和性别特定的基因组广泛关联研究（GWAS）从未有过报告。我们将使用严格的统计方法来识别特定性别的遗传危险因素对于OD。我们有非洲和非洲和可以分析和利用的具有GWAS和外显阵阵列数据的欧洲裔美国人具有公开可用的遗传和基因组学数据。这个大型SD队列已被评估使用药物依赖和酒精中毒的半结构化评估（SSADDA）乐器。在此提案中，由DSM标准计数定义的OD将是针对性的特征分析。该行政补充提案的总体目标是分析遗传我们为男女收集的数据以最有效地识别性别特异性的遗传变体。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Inviting in the Exome for Alcohol and Smoking Traits.

邀请外显子组研究酒精和吸烟特征。

DOI：
10.1016/j.biopsych.2019.04.005
发表时间：
2019
期刊：
Biological psychiatry
影响因子：
10.6
作者：
Gelernter,Joel
通讯作者：
Gelernter,Joel

Meta-analysis of 15 genome-wide linkage scans of smoking behavior.

DOI：
10.1016/j.biopsych.2009.08.028
发表时间：
2010-01-01
期刊：
BIOLOGICAL PSYCHIATRY
影响因子：
10.6
作者：
Han, Shizhong;Gelernter, Joel;Luo, Xingguang;Yang, Bao-Zhu
通讯作者：
Yang, Bao-Zhu

Sex-stratified gene-by-environment genome-wide interaction study of trauma, posttraumatic-stress, and suicidality.

DOI：
10.1016/j.ynstr.2021.100309
发表时间：
2021-05
期刊：
Neurobiology of stress
影响因子：
5
作者：
Wendt FR;Pathak GA;Levey DF;Nuñez YZ;Overstreet C;Tyrrell C;Adhikari K;De Angelis F;Tylee DS;Goswami A;Krystal JH;Abdallah CG;Stein MB;Kranzler HR;Gelernter J;Polimanti R
通讯作者：
Polimanti R

Genome-wide screen for heavy alcohol consumption.

针对大量饮酒的全基因组筛查。

DOI：
10.1186/1471-2156-4-s1-s106
发表时间：
2003
期刊：
BMC genetics [electronic resource].
影响因子：
0
作者：
Wyszynski,DiegoF;Panhuysen,CarolienI;Ma,Qianli;Yip,AgustinG;Wilcox,Marsha;Erlich,Porat;Farrer,LindsayA
通讯作者：
Farrer,LindsayA

A Preliminary Study of DBH (Encoding Dopamine Beta-Hydroxylase) Genetic Variation and Neural Correlates of Emotional and Motivational Processing in Individuals With and Without Pathological Gambling.

有或没有病态赌博个体的 DBH（编码多巴胺 β-羟化酶）遗传变异以及情绪和动机加工的神经相关性的初步研究。