Epidemiology of Gene-Alcohol Interactions and Lipids

描述(由申请人提供)：适度饮酒与降低冠心病风险有关。这些有益的影响最常见的归因于酒精诱导的血脂变化，尽管低至中等酒精摄入量对心脏保护作用的潜在机制尚不清楚。血脂水平受到多种因素的影响，包括环境因素(如酒精)和遗传因素，虽然这些因素中的每一个对血脂的独立影响已被广泛研究，但它们的联合影响研究较少，了解也较少。以前的研究主要利用候选基因的方法来研究脂代谢基因中预先选择的遗传变异；然而，随着多态发现、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SNPs集合。因此，现在有可能(也更有可能)利用全基因组关联方法来识别影响血脂的基因-酒精相互作用。ARIC研究[N~16,000]已经对跨越人类基因组的1,000,000个SNPs进行了基因分型，拟议的研究将利用该资源的全部范围来确定影响Lipd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]预先安排的合作来促进复制。进一步对最高复制HITS的基因/区域内的功能变异和/或TagSNPs进行基因分型将有助于我们识别与饮酒特异性相互作用影响血脂的假定功能变异 级别。 与公众健康相关：适度饮酒与降低冠心病风险有关，最显著的是通过酒精对血脂的有益影响。以前的研究主要使用候选基因方法来研究脂代谢基因中预先选择的遗传变异；然而，现在使用全基因组关联方法来识别影响血脂的基因-酒精相互作用是可能的(也更有可能)。ARIC研究已经对跨越人类基因组的100万个SNPs进行了基因分型，拟议的研究将利用这一可用资源的全部范围(以及两个独立的复制队列，CARDIA和DHS)来确定影响血脂水平的基因-酒精相互作用。进一步对最高复制HITS的基因/区域内的功能变异和/或TagSNPs进行基因分型，将有助于识别可能与饮酒相互作用影响血脂水平的功能变异。

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. PUBLIC HEALTH RELEVANCE: Moderate alcohol consumption has been associated with a reduction in the risk of CHD, most notably through the beneficial effects of alcohol on lipids. Previous studies have primarily utilized a candidate gene approach to investigate pre-selected genetic variation within lipid metabolism genes; however, it is now possible (and more plausible) to use a genome-wide association approach to identify gene-alcohol interactions influencing lipids. The ARIC study has been genotyped for >1,000,000 SNPs spanning the human genome, and the proposed research will leverage the full scope of this available resource (as well as two independent replication cohorts, CARDIA and DHS) to identify gene-alcohol interactions influencing lipid levels. Further genotyping of functional variants and/or TagSNPs within the genes/regions of the top replicated hits will aid in the identification of putative functional varints that specifically interact with alcohol consumption to influence lipid levels.