Abou-Sleiman P M, Hanna M G, Wood N W
Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
J Neurol Neurosurg Psychiatry. 2006 Dec;77(12):1302-4. doi: 10.1136/jnnp.2005.082024.
Genetic association studies offer a powerful approach to identify the multiple variants of small effect that modulate susceptibility to common, complex disease. They, however, have a poor reputation, mainly because of the consistent lack of replication of all but a few. Thousands of genetic studies have been carried out on multifactorial diseases in the past 30 years, yielding only about 50 variants that can be considered to be true positives. Although the positive studies show proof of principle, the multitude of negative studies indicate fundamental problems in the design and execution of association studies. Here, we discuss some of the more pertinent study design and data analysis issues which can affect the outcome of genetic association studies.
基因关联研究提供了一种强有力的方法，用以识别那些对常见复杂疾病易感性产生影响的、具有微小效应的多个变异。然而，它们的声誉不佳，主要原因是除了少数几个研究外，其他研究几乎都无法重复验证。在过去30年里，针对多因素疾病开展了数千项基因研究，结果仅产生了约50个可被视为真正阳性的变异。尽管阳性研究证明了其原理，但大量的阴性研究表明关联研究在设计和实施方面存在根本性问题。在此，我们讨论一些可能影响基因关联研究结果的更为相关的研究设计和数据分析问题。
