Establishment of genetic associations for complex diseases is independent of early study findings
Establishment of genetic associations for complex diseases is independent of early study findings
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DOI：
10.1038/sj.ejhg.5201227
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发表时间：
2004-09-01
影响因子：
5.2
通讯作者：
Ioannidis, JPA
中科院分区：
文献类型：
--
作者：
Trikalinos, TA;Ntzani, EE;Ioannidis, JPA
对复杂疾病进行了许多遗传关联研究。研究者强调正式的统计学显著性（P值= 3），早期发表的研究，或早期研究中的高统计学显著性具有任何预测能力，可以在随后的研究中建立或反驳遗传相关性的存在。在35个协会中，第一次研究是“积极的”，在15个协会中，超过一半的早期发表的报告是“积极的”。后续研究的平均发表率增加了1.71倍，首次报告为“阳性”。与后续研究的总结结果相比，第一份报告的敏感性和特异性分别为0.65和0.38，当考虑至少三项早期研究时，敏感性和特异性分别为0.40和0.73。当我们考虑估计的可归因分数和95%置信区间的覆盖率或更高水平的统计学显著性时，第一项研究的预测能力也很差。我们的结论是，虽然“积极”的发现，在第一次报告提供了强大的激励进行更多的研究，一个假定的遗传流行病学协会，统计学意义，甚至早期研究的影响的幅度不能充分预测最终建立的协会。相反，如果在早期的“负面”研究不足后放弃研究，许多真正的流行病学关联将被错过。
Numerous genetic association studies for complex diseases are performed. Investigators place emphasis on formal statistical significance (P-values = 3) early-published studies, or high statistical significance in early studies had any predictive ability for establishing or refuting the presence of the genetic association in subsequent research. In 35 associations, a first study was 'positive' and in 15 associations more than half of the early-published reports were 'positive'. The average publication rate of subsequent studies increased 1.71-fold with a 'positive' first report. When compared against the summary results of subsequent research, sensitivity and specificity were 0.65 and 0.38 for the first reports, and 0.40 and 0.73, respectively, when at least three early studies were considered. First studies also had poor predictive ability, when we considered the estimated attributable fraction and coverage of the 95% confidence interval thereof or higher levels of statistical significance. We conclude that although 'positive' findings in the very first reports provide strong incentive for conducting more studies on a putative genetic epidemiological association, the statistical significance or even the magnitude of the effect of early studies cannot adequately predict eventual establishment of an association. Conversely, many genuine epidemiological associations would be missed, if research were abandoned after early underpowered 'negative' studies.