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
• 负责人: Chunyu Liu
• 金额: $ 53.17万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10616528
• 关键词: Address; Alcohol consumption; Alcohols; American; Applications Grants; Biological Markers; Calories; Cardiovascular Diseases; Complex; Computer software; Coronary heart disease; DNA Methylation; Databases; Dimensions; Disease; Disease Outcome; Framingham Heart Study; Future; Gene Expression; Genes; Genotype-Tissue Expression Project; Goals; Healthy Eating; Human; Interdisciplinary Study; Investigation; Ischemic Stroke; Knowledge; Life Style; Measures; Mediating; Mediation; Medical; Mendelian randomization; Methods; Molecular; Molecular Profiling; Molecular Target; Multiomic Data; Myocardial Ischemia; Neurodegenerative Disorders; Participant; Pathway Analysis; Pathway interactions; Pattern; Phenotype; Plasma; Plasma Proteins; Prevention; Process; Proteins; Proteome; Proteomics; Recommendation; Resources; Risk Factors; Sampling; Testing; Treatment Cost; adjudication; alcohol abuse therapy; alcohol effect; bioinformatics tool; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular risk factor; causal variant; cohort; cost efficient; dietary guidelines; high throughput technology; metabolome; metabolomics; methylation biomarker; methylome; modifiable lifestyle factors; multidisciplinary; multiple omics; novel; polygenic risk score; public health priorities; random forest; transcriptome; transcriptomics

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

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: Nutrients
• 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: AGING-US
• 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: medRxiv : the preprint server for health sciences
• 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: Scientific reports
• 影响因子: 4.6

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: Human molecular genetics
• 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