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:10616528
- 负责人:
- 金额:$ 53.17万
- 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 MethylationDatabasesDimensionsDiseaseDisease OutcomeFramingham Heart StudyFutureGene ExpressionGenesGenotype-Tissue Expression ProjectGoalsHealthy EatingHumanInterdisciplinary StudyInvestigationIschemic StrokeKnowledgeLife StyleMeasuresMediatingMediationMedicalMendelian randomizationMethodsMolecularMolecular ProfilingMolecular TargetMultiomic DataMyocardial IschemiaNeurodegenerative DisordersParticipantPathway AnalysisPathway interactionsPatternPhenotypePlasmaPlasma ProteinsPreventionProcessProteinsProteomeProteomicsRecommendationResourcesRisk FactorsSamplingTestingTreatment Costadjudicationalcohol abuse therapyalcohol effectbioinformatics toolcardiovascular disorder preventioncardiovascular disorder riskcardiovascular risk factorcausal variantcohortcost efficientdietary guidelineshigh throughput technologymetabolomemetabolomicsmethylation biomarkermethylomemodifiable lifestyle factorsmultidisciplinarymultiple omicsnovelpolygenic risk scorepublic 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.
项目总结
项目成果
期刊论文数量(9)
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 between Taste Perception Profiles and Empirically Derived Dietary Patterns: An Exploratory Analysis among Older Adults with Metabolic Syndrome.
- DOI:10.3390/nu14010142
- 发表时间:2021-12-29
- 期刊:
- 影响因子:5.9
- 作者:Gervis JE;Fernández-Carrión R;Chui KKH;Ma J;Coltell O;Sorli JV;Asensio EM;Ortega-Azorín C;Pérez-Fidalgo JA;Portolés O;Lichtenstein AH;Corella D
- 通讯作者:Corella D
Alcohol consumption and epigenetic age acceleration across human adulthood.
- DOI:10.18632/aging.205153
- 发表时间:2023-10-26
- 期刊:
- 影响因子:5.2
- 作者:Wang, Mengyao;Li, Yi;Lai, Meng;Nannini, Drew R.;Hou, Lifang;Joehanes, Roby;Huan, Tianxiao;Levy, Daniel;Ma, Jiantao;Liu, Chunyu
- 通讯作者:Liu, Chunyu
Whole Genome DNA and RNA Sequencing of Whole Blood Elucidates the Genetic Architecture of Gene Expression Underlying a Wide Range of Diseases.
全血的全基因组 DNA 和 RNA 测序阐明了多种疾病背后的基因表达的遗传结构。
- DOI:10.1101/2022.04.13.22273841
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:Liu,Chunyu;Joehanes,Roby;Ma,Jiantao;Wang,Yuxuan;Sun,Xianbang;Keshawarz,Amena;Sooda,Meera;Huan,Tianxiao;Hwang,Shih-Jen;Bui,Helena;Tejada,Brandon;Munson,PeterJ;Cumhur,Demirkale;Heard-Costa,NancyL;Pitsillides,AchilleasN;Pelos
- 通讯作者:Pelos
Elucidating the genetic architecture of DNA methylation to identify promising molecular mechanisms of disease.
阐明DNA甲基化的遗传结构,以鉴定有希望的疾病分子机制。
- DOI:10.1038/s41598-022-24100-0
- 发表时间:2022-11-15
- 期刊:
- 影响因子:4.6
- 作者:
- 通讯作者:
Blood transcriptomic biomarkers of alcohol consumption and cardiovascular disease risk factors: the Framingham Heart Study.
饮酒和心血管疾病危险因素的血液转录组生物标志物:弗雷明汉心脏研究。
- DOI:10.1093/hmg/ddac237
- 发表时间:2023
- 期刊:
- 影响因子:3.5
- 作者:Ma,Jiantao;Huang,Allen;Yan,Kaiyu;Li,Yi;Sun,Xianbang;Joehanes,Roby;Huan,Tianxiao;Levy,Daniel;Liu,Chunyu
- 通讯作者:Liu,Chunyu
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Chunyu Liu的其他文献
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{{ 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:
$ 53.17万 - 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:
$ 53.17万 - 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:
10436830 - 财政年份:2021
- 资助金额:
$ 53.17万 - 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:
$ 53.17万 - 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:
$ 53.17万 - 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:
$ 53.17万 - 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:
$ 53.17万 - 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:
$ 53.17万 - 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:
$ 53.17万 - 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:
$ 53.17万 - 项目类别:
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