How to Use an Article About Genetic Association B: Are the Results of the Study Valid?
How to Use an Article About Genetic Association B: Are the Results of the Study Valid?
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DOI：
10.1001/jama.2008.946
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发表时间：
2009-01-14
影响因子：
120.7
通讯作者：
Guyatt, Gordon
中科院分区：
文献类型：
--
作者：
Attia, John;Ioannidis, John P. A.;Guyatt, Gordon
在本系列的第一篇文章中，我们回顾了理解遗传关联研究所必需的基本遗传学概念。在这第二篇文章中，我们列举了判断这些研究的有效性的主要问题，作为关键的评估问题。疾病的表型是否由不了解遗传信息的人正确定义和准确记录？疾病组和非疾病组之间的任何潜在差异，特别是种族差异，是否得到了适当的解决？在遗传学研究中，假关联的一个潜在原因是病例和对照之间的种族差异，这种情况称为人群分层。遗传变异的测量是否公正和准确？DNA序列变异的测定方法并不完善，可能存在一定的测量误差。基因型比例是否符合哈代-温伯格平衡？这个关于基因组分布的简单数学规则可能是检查阅读DNA信息中错误的一种方法。研究者是否调整了多重比较的推论？考虑到全基因组关联研究中测试的数千种遗传标记，假阳性和假阴性结果的可能性比传统医学研究高得多，寻找结果的重复性尤为重要。
In the first article of this series, we reviewed the basic genetics concepts necessary to understand genetic association studies. In this second article, we enumerate the major issues in judging the validity of these studies, framed as critical appraisal questions. Was the disease phenotype properly defined and accurately recorded by someone blind to the genetic information? Have any potential differences between disease and nondisease groups, particularly ethnicity, been properly addressed? In genetic studies, one potential cause of spurious associations is differences between cases and controls in ethnicity, a situation termed population stratification. Was measurement of the genetic variants unbiased and accurate? Methods for determining DNA sequence variation are not perfect and may have some measurement error. Do the genotype proportions observe Hardy- Weinberg equilibrium? This simple mathematic rule about the distribution of genetic groups may be one way to check for errors in reading DNA information. Have the investigators adjusted their inferences for multiple comparisons? Given the thousands of genetic markers tested in genome- wide association studies, the potential for false- positive and false-negative results is much higher than in traditional medical studies, and it is particularly important to look for replication of results.