Epidemiology of Gene-Alcohol Interactions and Lipids

描述（由申请人提供）：适度饮酒与冠心病风险降低有关。这些有益的影响通常归因于酒精引起的脂质变化，尽管低至中度饮酒对心脏保护作用的机制尚不清楚。脂质水平受到多种因素的影响，包括环境（如酒精）和遗传因素，虽然这些因素中的每一个对脂质的独立影响已被广泛研究，但它们的综合影响研究较少，也不太清楚。以前的研究主要是利用候选基因方法来研究脂质代谢基因中预先选择的遗传变异；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跨越人类基因组的全基因组snp集合。因此，现在利用全基因组关联方法来鉴定影响脂质的基因-酒精相互作用是可能的（而且更合理）。ARIC研究[N~16,000]已经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这一资源来确定影响血脂水平的基因-酒精相互作用，并通过与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了复制。进一步对顶级复制点基因/区域内的功能变异和/或标签snp进行基因分型，将有助于我们识别与酒精消耗特异性相互作用以影响脂质的假定功能变异

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.