Genomics of Alcohol Withdrawal and Treatment Response to Benzodiazepines

酒精戒断的基因组学和苯二氮卓类药物的治疗反应

基本信息

  • 批准号:
    10497622
  • 负责人:
  • 金额:
    $ 54.85万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-05-01 至 2027-04-30
  • 项目状态:
    未结题

项目摘要

ABSTRACT Alcohol withdrawal is a critical component of development and persistence of addiction to alcohol and a cause for significant morbidity and mortality in patients with alcohol use disorders (AUD). Introduction of benzodiazepines resulted in reduced severity of alcohol withdrawal syndrome (AWS), and decreased mortality and frequency of complications. While research suggests involvement of certain neurotransmitter systems in the neurobiology of AWS, genetic markers associated with predisposition to AWS and its treatment response remain unknown. We therefore propose to perform comprehensive genetic analyses, including genome-wide association studies (GWASs), to identify genetic markers of AWS risk and response to benzodiazepine treatment of AWS. The proposed analyses will constitute the largest GWAS of AWS to date, with a sample size of AUD subjects 10 times larger than the only previously published AWS GWAS, and the first GWAS of benzodiazepine response. We will also investigate sex differences in genetic effects on AWS and response to its treatment. Our study will involve advanced analyses, including assessment of SNP-based heritability of AWS along with gene and pathway-level analyses (including drug-target enrichment) and fine-mapping to detect relevant genetic effects. We will also use polygenic risk scores to determine if genetic load for AUD-related traits is associated with AWS. The proposed study is aligned with NIAAA policy, which states that GWAS is “the preferred approach for the identification of and the confirmation of genes that harbor variants that contribute to AUD and related phenotypes, since results from these studies will likely provide potential insights into translational studies and new therapeutic targets”. The proposed research also supports NIH efforts to increase awareness and attention to sex and gender in research. Our preliminary data and power calculations demonstrate that analysis of available data is expected to identify common genetic variants associated with AWS. Discovery of genetic variants that impact the risk of AWS will generate knowledge on its neurobiology and ultimately contribute to the development of tools for the identification of patients at risk and selection of treatment options based on an understanding of inter- individual differences in sensitivity to this central component of AUD. This line of research may also contribute to development of new AUD treatment approaches aimed to restore physiological dysfunction associated with those genetic variants.
摘要

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Joanna M Biernacka其他文献

450. In Bipolar Disorder, SLC1A2 Promoter Hypomethylation is Associated with Binge Eating Disorder and Nicotine Dependance
  • DOI:
    10.1016/j.biopsych.2017.02.934
  • 发表时间:
    2017-05-15
  • 期刊:
  • 影响因子:
  • 作者:
    Marin Veldic;Yun-Fang Jia;YuBin Choi;Jennifer R Ayers-Ringler;Joanna M Biernacka;Jennifer R Geske;Susan McElroy;Mark Frye;Doo-Sup Choi
  • 通讯作者:
    Doo-Sup Choi
Gene set analysis of SNP data: benefits, challenges, and future directions
单核苷酸多态性数据的基因集分析:益处、挑战和未来方向
  • DOI:
    10.1038/ejhg.2011.57
  • 发表时间:
    2011-04-13
  • 期刊:
  • 影响因子:
    4.600
  • 作者:
    Brooke L Fridley;Joanna M Biernacka
  • 通讯作者:
    Joanna M Biernacka

Joanna M Biernacka的其他文献

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{{ truncateString('Joanna M Biernacka', 18)}}的其他基金

2/4: Leveraging EHR-linked biobanks for deep phenotyping, polygenic risk score modeling, and outcomes analysis in psychiatric disorders
2/4:利用与 EHR 相关的生物库进行精神疾病的深度表型分析、多基因风险评分建模和结果分析
  • 批准号:
    10176262
  • 财政年份:
    2019
  • 资助金额:
    $ 54.85万
  • 项目类别:
2/4: Leveraging EHR-linked biobanks for deep phenotyping, polygenic risk score modeling, and outcomes analysis in psychiatric disorders
2/4:利用与 EHR 相关的生物库进行精神疾病的深度表型分析、多基因风险评分建模和结果分析
  • 批准号:
    10406330
  • 财政年份:
    2019
  • 资助金额:
    $ 54.85万
  • 项目类别:
PHARMACOGENOMICS OF ACAMPROSATE TREATMENT OUTCOME
阿坎酸治疗结果的药物基因组学
  • 批准号:
    10477435
  • 财政年份:
    2018
  • 资助金额:
    $ 54.85万
  • 项目类别:
PHARMACOGENOMICS OF ACAMPROSATE TREATMENT OUTCOME
阿坎酸治疗结果的药物基因组学
  • 批准号:
    10007092
  • 财政年份:
    2018
  • 资助金额:
    $ 54.85万
  • 项目类别:
PHARMACOGENOMICS OF ACAMPROSATE TREATMENT OUTCOME
阿坎酸治疗结果的药物基因组学
  • 批准号:
    9767646
  • 财政年份:
    2018
  • 资助金额:
    $ 54.85万
  • 项目类别:
PHARMACOGENOMICS OF ACAMPROSATE TREATMENT OUTCOME
阿坎酸治疗结果的药物基因组学
  • 批准号:
    10000815
  • 财政年份:
    2018
  • 资助金额:
    $ 54.85万
  • 项目类别:
Pharmacogenomics of Treatment Outcomes in Alcohol Use Disorders
酒精使用障碍治疗结果的药物基因组学
  • 批准号:
    9164922
  • 财政年份:
    2016
  • 资助金额:
    $ 54.85万
  • 项目类别:
Pharmacogenomics of Treatment Outcomes in Alcohol Use Disorders
酒精使用障碍治疗结果的药物基因组学
  • 批准号:
    9315679
  • 财政年份:
    2016
  • 资助金额:
    $ 54.85万
  • 项目类别:
Methods for detecting interacting risk factors for addictions
检测成瘾相互作用危险因素的方法
  • 批准号:
    8038314
  • 财政年份:
    2010
  • 资助金额:
    $ 54.85万
  • 项目类别:
Methods for detecting interacting risk factors for addictions
检测成瘾相互作用危险因素的方法
  • 批准号:
    7897098
  • 财政年份:
    2010
  • 资助金额:
    $ 54.85万
  • 项目类别:

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