Pruissen D Martijn O, Kappelle L Jaap, Rosendaal Frits R, Algra Ale
Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
Cerebrovasc Dis. 2009;27(3):290-4. doi: 10.1159/000199467. Epub 2009 Feb 6.
Although hundreds of genetic association studies of ischaemic stroke have been published, the failure to replicate associations has led to scepticism about their findings. Possible explanations for this failure are: (1) a false-positive association in the initial study; (2) a false-negative association in a replication study; (3) methodological differences (e.g. study populations or study designs). We review underlying causes for replication failure, such as small sample size, multiple testing and publication bias, and methods to deal with these problems. We also make suggestions about the design of genetic association studies in ischaemic stroke with regard to stroke subtype classification, candidate pathways, subgroups, intermediate phenotypes and potential clinical impact.
尽管已经发表了数百项关于缺血性中风的基因关联研究，但关联结果未能得到重复验证，这使得人们对这些研究结果产生了怀疑。这种未能重复验证的可能原因包括：（1）初始研究中存在假阳性关联；（2）重复研究中存在假阴性关联；（3）方法学差异（如研究人群或研究设计）。我们回顾了重复验证失败的潜在原因，如样本量小、多重检验和发表偏倚，以及处理这些问题的方法。我们还就缺血性中风基因关联研究的设计，在中风亚型分类、候选通路、亚组、中间表型和潜在临床影响方面提出了建议。
