Trans-omic Analysis of Alcohol Consumption and its Relation to Cardiovascular Disease
酒精消耗及其与心血管疾病关系的跨组学分析
基本信息
- 批准号:10436830
- 负责人:
- 金额:$ 54.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAlcohol consumptionAlcoholsAmericanApplications GrantsBiological MarkersCaloriesCardiovascular DiseasesComplexComputer softwareCoronary heart diseaseDNA MethylationDatabasesDimensionsDisease OutcomeFramingham Heart StudyFutureGene ExpressionGenesGenotype-Tissue Expression ProjectGoalsHealthy EatingHumanInterdisciplinary StudyInvestigationIschemic StrokeKnowledgeLife StyleMeasuresMediatingMediationMedicalMendelian randomizationMethodsMolecularMolecular ProfilingMolecular TargetMultiomic DataNeurodegenerative DisordersParticipantPathway AnalysisPathway interactionsPatternPhenotypePlasmaPlasma ProteinsPreventionProcessProteinsProteomeProteomicsResourcesRisk FactorsSamplingTestingTreatment Costadjudicatealcohol abuse therapyalcohol effectbioinformatics toolcardiovascular disorder preventioncardiovascular disorder riskcardiovascular risk factorcausal variantcohortcost efficientdietary guidelineshigh throughput technologymetabolomemetabolomicsmethylation biomarkermethylomemodifiable lifestyle factorsmultidisciplinarymultiple omicsnovelpolygenic risk scoreprotein metabolitepublic health prioritiesrandom foresttranscriptometranscriptomics
项目摘要
PROJECT SUMMARY
Alcohol consumption is an important modifiable lifestyle risk factor for cardiovascular disease (CVD). Advances
in high-throughput technologies have made it possible to measure and analyze a variety of ‘omics’, that is, DNA
methylation (methylome), gene expression (transcriptome), protein (proteome) and metabolite (metabolome), in
relation to alcohol consumption and CVD in a cost-efficient manner. In this grant proposal, we will test the
hypothesis that alcohol consumption alters multiple molecular processes across different “omics” dimensions
and these molecular intermediates mediate alcohol’s effects on CVD.
To test this hypothesis, we will assemble a multidisciplinary team to test five Specific Aims. In Aim 1, we will first
identify alcohol-associated transcriptomic markers. We will then examine the associations of alcohol-associated
transcriptomic markers with incident CVD (fatal and nonfatal coronary heart disease and ischemic stroke), and
test whether these transcriptomic markers mediate the effect of alcohol intake on incident CVD. We will construct
polygenic risk scores to examine the potential causal relationships between alcohol intake, transcriptomic
markers, and incident CVD. We will also conduct a two-sample Mendelian randomization (MR) analysis to further
test and quantify the causal relationships. In Aims 2 and 3, we will identify alcohol-associated proteomic (Aim 2)
and metabolomic (Aim 3) markers and will test the relationship between alcohol, omics markers and CVD using
similar methods outlined in Aim 1. Many alcohol-associated DNA methylation markers have been identified by
our prior study in >13,000 participants. Therefore, in Aim 4, we will examine the relations of alcohol-associated
DNA methylation markers with incident CVD using similar methods outlined in Aim 1. In Aim 5, we will integrate
alcohol-associated multi-omics markers to identify key pathways and multi-omics modules associated with
alcohol intake and CVD. We will perform Random Forest analysis to identify additional alcohol-associated multi-
omics markers. We will also perform network analyses to identify modules of alcohol-associated multi-omics
markers. We will examine the relationships between these identified multi-omics markers with incident CVD, and
will functionally annotate these markers using bioinformatics tools (e.g., ENCODE, GTEx, Human Metabolome
Database, and UniProt). With the completion of this project, we will highlight the novel molecular targets for both
alcohol-associated CVD risk prevention and treatment. In addition, we will generate a multi-omics biomarker
database of alcohol intake with tailored software to facilitate the future investigations of alcohol’s relations with
other non-communicable diseases such as neurodegenerative diseases.
项目摘要
饮酒是心血管疾病(CVD)的一个重要的可改变的生活方式风险因素。进展
高通量技术的发展使得测量和分析各种“组学”,即DNA,
甲基化(甲基化组),基因表达(转录组),蛋白质(蛋白质组)和代谢物(代谢组),
以具有成本效益的方式减少酒精消费和CVD的关系。在这份拨款申请中,我们将测试
饮酒改变不同“组学”维度的多个分子过程的假说
这些分子中间体介导了酒精对CVD的影响。
为了验证这一假设,我们将组建一个多学科团队来测试五个特定目标。在目标1中,我们将首先
鉴定酒精相关转录组标记。然后,我们将研究与酒精相关的
与CVD事件(致死性和非致死性冠心病和缺血性卒中)相关的转录组学标志物,以及
测试这些转录组标志物是否介导酒精摄入对CVD事件的影响。了建设一
多基因风险评分,以检查酒精摄入量、转录组学和遗传学之间的潜在因果关系。
标记物和意外心血管疾病我们还将进行双样本孟德尔随机化(MR)分析,以进一步
测试并量化因果关系。在目标2和3中,我们将确定酒精相关蛋白质组学(目标2)
和代谢组学(Aim 3)标记物,并将使用
类似于目标1中概述的方法。许多与酒精相关的DNA甲基化标志物已经被鉴定,
我们之前在13,000名参与者中进行的研究。因此,在目标4中,我们将研究酒精相关的关系,
使用目标1中概述的类似方法,使用发生CVD的DNA甲基化标志物。在目标5中,我们将
酒精相关的多组学标记物,以确定与酒精相关的关键途径和多组学模块。
酒精摄入和心血管疾病我们将进行随机森林分析,以确定其他与酒精相关的多-
组学标记。我们还将进行网络分析,以确定酒精相关的多组学模块
标记。我们将研究这些确定的多组学标记物与CVD事件之间的关系,
将使用生物信息学工具(例如,ENCODE,GTEx,人代谢组
数据库和UniProt)。随着该项目的完成,我们将重点关注这两个新的分子靶点
酒精相关的CVD风险预防和治疗。此外,我们将生成多组学生物标志物,
酒精摄入量数据库,并配有专门的软件,以方便今后调查酒精与
其他非传染性疾病,如神经退行性疾病。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Chunyu Liu其他文献
Chunyu Liu的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Chunyu Liu', 18)}}的其他基金
Gene Expression Regulation in Brains of East Asian, African, and European Descent Explains Schizophrenia GWAS in Diverse Populations.
东亚、非洲和欧洲血统大脑中的基因表达调控解释了不同人群中的精神分裂症 GWAS。
- 批准号:
10382057 - 财政年份:2022
- 资助金额:
$ 54.36万 - 项目类别:
Gene Expression Regulation in Brains of East Asian, African, and European Descent Explains Schizophrenia GWAS in Diverse Populations.
东亚、非洲和欧洲血统大脑中的基因表达调控解释了不同人群中的精神分裂症 GWAS。
- 批准号:
10597054 - 财政年份:2022
- 资助金额:
$ 54.36万 - 项目类别:
Mitochondrial DNA, Nuclear DNA Methylation, and Cardiometabolic Disease Traits
线粒体 DNA、核 DNA 甲基化和心脏代谢疾病特征
- 批准号:
10646401 - 财政年份:2021
- 资助金额:
$ 54.36万 - 项目类别:
Mitochondrial DNA, Nuclear DNA Methylation, and Cardiometabolic Disease Traits
线粒体 DNA、核 DNA 甲基化和心脏代谢疾病特征
- 批准号:
10475148 - 财政年份:2021
- 资助金额:
$ 54.36万 - 项目类别:
Mitochondrial DNA, Nuclear DNA Methylation, and Cardiometabolic Disease Traits
线粒体 DNA、核 DNA 甲基化和心脏代谢疾病特征
- 批准号:
10297789 - 财政年份:2021
- 资助金额:
$ 54.36万 - 项目类别:
Trans-omic Analysis of Alcohol Consumption and its Relation to Cardiovascular Disease
酒精消耗及其与心血管疾病关系的跨组学分析
- 批准号:
10616528 - 财政年份:2021
- 资助金额:
$ 54.36万 - 项目类别:
Trans-omic Analysis of Alcohol Consumption and its Relation to Cardiovascular Disease
酒精消耗及其与心血管疾病关系的跨组学分析
- 批准号:
10209156 - 财政年份:2021
- 资助金额:
$ 54.36万 - 项目类别:
1/3 High-resolution mapping of cell type-specific DNA (hydroxy)methylation in the human brain during postnatal development and in psychiatric disease.
1/3 出生后发育和精神疾病期间人脑中细胞类型特异性 DNA(羟基)甲基化的高分辨率图谱。
- 批准号:
10576891 - 财政年份:2020
- 资助金额:
$ 54.36万 - 项目类别:
1/3 High-resolution mapping of cell type-specific DNA (hydroxy)methylation in the human brain during postnatal development and in psychiatric disease.
1/3 出生后发育和精神疾病期间人脑中细胞类型特异性 DNA(羟基)甲基化的高分辨率图谱。
- 批准号:
10360523 - 财政年份:2020
- 资助金额:
$ 54.36万 - 项目类别:
Mitochondrial DNA Copy Number and Sequence Variation in Relation to Age, Alzheimer's Disease Related Phenotypes and Age-related Metabolic Traits
线粒体 DNA 拷贝数和序列变异与年龄、阿尔茨海默病相关表型和年龄相关代谢特征的关系
- 批准号:
10212947 - 财政年份:2018
- 资助金额:
$ 54.36万 - 项目类别:
相似海外基金
Molecular mechanisms of carcinogenesis and symptoms associated with alcohol consumption
致癌的分子机制和饮酒相关症状
- 批准号:
23K05734 - 财政年份:2023
- 资助金额:
$ 54.36万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The investigation of chronic alcohol consumption enhanced aging colon in elder mice and the mechanism of suppressed on aging colon tissues by sesame lignans continuous intake
长期饮酒促进老年小鼠结肠衰老的研究及持续摄入芝麻木脂素抑制结肠组织衰老的机制
- 批准号:
23K10904 - 财政年份:2023
- 资助金额:
$ 54.36万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Internal Sources of Minority Stress and Alcohol Consumption
少数群体压力和饮酒的内部根源
- 批准号:
10742318 - 财政年份:2023
- 资助金额:
$ 54.36万 - 项目类别:
Characterizing the Relationship Between Alcohol Consumption and Neuron-Derived Exosomal MicroRNA Cargo in an Adolescent-Young Adult Twin Cohort
青少年双胞胎队列中酒精消耗与神经元衍生的外泌体 MicroRNA 货物之间关系的表征
- 批准号:
10452928 - 财政年份:2022
- 资助金额:
$ 54.36万 - 项目类别:
Endocrine regulation of alcohol consumption and fear learning
饮酒和恐惧学习的内分泌调节
- 批准号:
10483780 - 财政年份:2022
- 资助金额:
$ 54.36万 - 项目类别:
The impact of friends sharing different modalities of alcohol-related social media content on alcohol consumption: A longitudinal examination of changes in content shared by social networks over time
朋友分享不同形式的酒精相关社交媒体内容对饮酒的影响:对社交网络分享内容随时间变化的纵向研究
- 批准号:
10534428 - 财政年份:2022
- 资助金额:
$ 54.36万 - 项目类别:
Cannabis' Impact on Alcohol Consumption: Integrating Laboratory and Ecological Momentary Assessment Methods
大麻对酒精消费的影响:整合实验室和生态瞬时评估方法
- 批准号:
10339931 - 财政年份:2022
- 资助金额:
$ 54.36万 - 项目类别:
Chronic alcohol consumption results in elevated Autotaxin levels that suppress anti-tumor immunity
长期饮酒会导致自分泌运动因子水平升高,从而抑制抗肿瘤免疫力
- 批准号:
10370159 - 财政年份:2022
- 资助金额:
$ 54.36万 - 项目类别:
Cannabis' Impact on Alcohol Consumption: Integrating Laboratory and Ecological Momentary Assessment Methods
大麻对酒精消费的影响:整合实验室和生态瞬时评估方法
- 批准号:
10595096 - 财政年份:2022
- 资助金额:
$ 54.36万 - 项目类别:
Technology-based assessments and intervention to reduce alcohol consumption and improve HIV viral suppression in the Florida Cohort
基于技术的评估和干预,以减少佛罗里达队列的饮酒量并改善艾滋病病毒抑制
- 批准号:
10707386 - 财政年份:2022
- 资助金额:
$ 54.36万 - 项目类别: