Carey G
Institute for Behavioral Genetics, University of Colorado, Boulder 80309-0345, USA.
Am J Med Genet. 1994 Dec 15;54(4):311-7. doi: 10.1002/ajmg.1320540407.
Recent analysis of the candidate gene, association study for psychiatric disorders have concluded that most statistically significant results are likely to be false positives because there are a large number of potential candidate loci and a low a priori probability that a given candidate locus will in fact be trait relevant. Hence, it was recommended that the alpha level (P level) be lowered for association studies. The present study demonstrates that lowering the alpha level to some fixed, predetermined value is not a recommended strategy. Rather, the probability of false positives (and false negatives) depends on such parameters as the prevalence of the disorder, the prevalence of the genotypes at the candidate locus, and the relative risk. In some areas of the parameter space, the adjustment to alpha may be modest. In other areas, however, even the requirement of one or more independent replications of the original results gives false positive rates exceeding 80% or 90%. Hence, the P levels required to minimize false positives may have to be changed from one statistical test to another even within the same study. A procedure for adjusting the probability level for a test of association between genotypes and a disorder is given.
近期针对精神疾病的候选基因关联研究分析得出结论，大多数具有统计学显著意义的结果可能是假阳性，因为存在大量潜在的候选基因座，且给定候选基因座实际上与性状相关的先验概率较低。因此，有人建议在关联研究中降低显著性水平（P值）。本研究表明，将显著性水平降低到某个固定的预定值并非推荐策略。相反，假阳性（和假阴性）的概率取决于诸如疾病患病率、候选基因座处基因型的患病率以及相对风险等参数。在参数空间的某些区域，对显著性水平的调整可能较小。然而，在其他区域，即使要求对原始结果进行一次或多次独立重复验证，假阳性率仍会超过80%或90%。因此，即使在同一研究中，为使假阳性最小化所需的P值可能也会因统计检验的不同而改变。本文给出了一种调整基因型与疾病关联检验概率水平的方法。
