Measuring alcohol consumption for genomic meta-analyses of alcohol intake: opportunities and challenges
Measuring alcohol consumption for genomic meta-analyses of alcohol intake: opportunities and challenges
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DOI：
10.3945/ajcn.111.015545
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发表时间：
2012-03-01
影响因子：
7.1
通讯作者：
Bierut, Laura J.
中科院分区：
文献类型：
--
作者：
Agrawal, Arpana;Freedman, Neal D.;Bierut, Laura J.
虽然适度饮酒可能对健康有益，但过度饮酒会导致许多重要的急性和慢性疾病，是美国可预防死亡的第三大元凶。双胞胎研究表明，饮酒模式是可遗传的（50%）；然而，适度效应大小的多种遗传变异可能导致这种遗传变异。全基因组关联研究为发现导致饮酒量变化的基因位点提供了一种工具。通过对多个研究进行荟萃分析，有机会确定影响不大的易感位点。然而，现有的研究评估了酒精使用的许多不同方面，例如将典型饮酒与重度饮酒进行比较，这些不同的评估可能难以调和。此外，许多研究缺乏区分终生戒酒和最近戒酒的能力，也缺乏评估一周内饮酒模式的能力，而且各种各样的担忧围绕着制定一种通用的酒精摄入量综合衡量标准的适当性。结合这些酒精摄入量的测量可能导致异质性和暴露错误分类，导致功率降低，并影响遗传关联信号的大小。在这篇综述中，我们讨论了与协调来自不同评估工具的研究的酒精消费数据相关的挑战，特别关注大规模基因研究。J·克林·努尔2012；95: 539 - 47岁。
Whereas moderate drinking may have health benefits, excessive alcohol consumption causes many important acute and chronic diseases and is the third leading contributor to preventable death in the United States. Twin studies suggest that alcohol-consumption patterns are heritable (50%); however, multiple genetic variants of modest effect size are likely to contribute to this heritable variation. Genome-wide association studies provide a tool for discovering genetic loci that contribute to variations in alcohol consumption. Opportunities exist to identify susceptibility loci with modest effect by meta-analyzing together multiple studies. However, existing studies assessed many different aspects of alcohol use, such as typical compared with heavy drinking, and these different assessments can be difficult to reconcile. In addition, many studies lack the ability to distinguish between lifetime and recent abstention or to assess the pattern of drinking during the week, and a variety of such concerns surround the appropriateness of developing a common summary measure of alcohol intake. Combining such measures of alcohol intake can cause heterogeneity and exposure misclassification, cause a reduction in power, and affect the magnitude of genetic association signals. In this review, we discuss the challenges associated with harmonizing alcohol-consumption data from studies with widely different assessment instruments, with a particular focus on large-scale genetic studies. Am J Clin Nutr 2012; 95: 539-47.