Epidemiology of Gene-Alcohol Interactions and Lipids

基因-酒精相互作用和脂质的流行病学

• 批准号: 8544145
• 负责人: Alanna C Morrison
• 金额: $ 7.07万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8544145
• 关键词: Affect; African American; Alcohol consumption; Alcohols; Atherosclerosis; Candidate Disease Gene; Caucasoid Race; Clinical; Collaborations; Collection; Communities; Coronary artery; Coronary heart disease; Data; Data Analyses; Development; Epidemiology; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genotype; Heart; High Density Lipoprotein Cholesterol; Human Genome; LDL Cholesterol Lipoproteins; Lipids; Longitudinal Studies; Measures; Modification; National Institute on Alcohol Abuse and Alcoholism; Plasma; Population Genetics; Prevention; Research; Resources; Risk; Sampling; Single Nucleotide Polymorphism; Statistical Methods; Triglycerides; Variant; alcohol effect; alcohol research; cohort; follow-up; genome wide association study; genome-wide; genotyping technology; interest; lipid metabolism; population based; public health relevance; response; success; young adult

DESCRIPTION (provided by applicant): Moderate alcohol consumption has been associated with a reduction in the risk of CHD. These beneficial effects are most commonly attributed to alcohol-induced changes in lipids, although the mechanisms underlying the cardioprotective effects of low to moderate alcohol consumption are unknown. Lipid levels are influenced by multiple factors, including environmental (e.g. alcohol) and genetic factors, and while the independent effects of each of these factors on lipids have been widely studied, their combined effects have been less studied and are less understood. Previous studies have primarily utilized a candidate gene approach to investigate pre-selected genetic variation within lipid metabolism genes; however, advances in polymorphism discovery, population genetics and genotyping technologies have yielded a genome-wide collection of SNPs that span the human genome. Therefore, it is now possible (and more plausible) to utilize a genome-wide association approach to identify gene-alcohol interactions influencing lipids. The ARIC study [N~16,000] has been genotyped for >1,000,000 SNPs spanning the human genome, and the proposed research will leverage the full scope of this resource to identify gene-alcohol interactions influencing lipd levels, with replication facilitated through pre-arranged collaborations with the CARDIA Study [N~3,750] and the Dallas Heart Study [N~3,550]. Further genotyping of functional variants and/or TagSNPs within the genes/regions of the top replicated hits will aid in our identification o putative functional variants that specifically interact with alcohol consumption to influence lipid levels.

描述（由申请人提供）：适度饮酒与CHD风险降低相关。这些有益的作用最常见的归因于酒精诱导的脂质变化，尽管低至中度饮酒的心脏保护作用的机制尚不清楚。血脂水平受多种因素影响，包括环境（如酒精）和遗传因素，虽然这些因素对血脂的独立影响已被广泛研究，但其综合影响研究较少，了解较少。以前的研究主要利用候选基因的方法来调查预先选择的脂质代谢基因内的遗传变异;然而，多态性发现，群体遗传学和基因分型技术的进步已经产生了一个全基因组的SNP集合，跨越人类基因组。因此，现在有可能（也更合理）利用全基因组关联方法来识别影响脂质的基因-酒精相互作用。ARIC研究[N~ 16，000]已对跨越人类基因组的> 1，000，000个SNP进行了基因分型，拟议的研究将充分利用该资源来确定影响lipd水平的基因-酒精相互作用，通过与CARDIA研究[N~ 3，750]和达拉斯心脏研究[N~ 3，550]预先安排的合作促进复制。在最高复制命中的基因/区域内的功能变体和/或TagSNP的进一步基因分型将有助于我们鉴定与酒精消耗特异性相互作用以影响脂质代谢的推定功能变体。 程度.