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）：中等饮酒与降低CHD风险的降低有关。这些有益的作用通常归因于酒精诱导的脂质变化，尽管低至中度酒精消耗的心脏保护作用的基础机制尚不清楚。脂质水平受到多种因素的影响，包括环境（例如酒精）和遗传因素，尽管这些因素中的每一个对脂质的独立作用进行了广泛的研究，但其组合效应的研究较少，并且不了解。先前的研究主要利用一种候选基因方法来研究脂质代谢基因内预选的遗传变异。然而，多态性发现，种群遗传学和基因分型技术的进步已经产生了跨越人类基因组的全基因组的SNP。因此，现在有可能（更合理）利用全基因组关联方法来识别影响脂质的基因醇相互作用。 ARIC研究[n〜16,000]的基因分型以> 1,000,000个SNP跨越人类的基因组，而拟议的研究将利用该资源的全部范围来识别影响LIPD水平的基因 - 酒精相互作用，并通过与Cardia研究的预处理协作促进了与Cardia研究[N〜3,750]和DALLAS HEATS和DALLAS HEATS和DALLAS HEATS和DALLAS HEATS的复制促进。在顶部复制命中的基因/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的识别o推定的功能变体，这些功能变体专门与酒精消耗相互作用以影响脂质 水平。