Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA.
Am J Clin Nutr. 2012 Mar;95(3):539-47. doi: 10.3945/ajcn.111.015545. Epub 2012 Feb 1.
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.
虽然适量饮酒可能对健康有益,但过量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主要原因。双胞胎研究表明,饮酒模式是可遗传的(50%);然而,许多遗传变异体可能对这种可遗传的变异有影响,但效应大小适中。全基因组关联研究为发现导致饮酒量变化的遗传基因座提供了一种工具。通过对多个研究进行荟萃分析,有机会确定具有适度影响的易感基因座。然而,现有的研究评估了饮酒的许多不同方面,例如与大量饮酒相比的典型饮酒,并且这些不同的评估可能难以协调。此外,许多研究缺乏区分终生和近期戒酒或评估一周内饮酒模式的能力,并且围绕制定共同的酒精摄入量综合衡量标准的适当性存在各种担忧。将这些酒精摄入量衡量标准结合起来可能会导致异质性和暴露错误分类,降低效力,并影响遗传关联信号的大小。在这篇综述中,我们讨论了协调具有广泛不同评估工具的研究中的饮酒数据所面临的挑战,特别是在大规模遗传研究方面。