Epidemiology of Gene-Alcohol Interactions and Lipids

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. 公共卫生相关性：适度饮酒与降低冠心病风险有关，最明显的是通过酒精对脂质的有益影响。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，但是，现在有可能（更合理）使用全基因组关联的方法来确定基因-酒精相互作用影响脂质。ARIC研究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。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鉴定与酒精消耗特异性相互作用以影响脂质水平的推定功能变体。

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.