Genetic associations in large versus small studies: an empirical assessment
Genetic associations in large versus small studies: an empirical assessment
复制标题
DOI：
10.1016/s0140-6736(03)12516-0
复制
发表时间：
2003-02-15
期刊：
影响因子：
168.9
通讯作者：
Contopoulos-Ioannidis, DG
中科院分区：
文献类型：
--
作者：
Ioannidis, JPA;Trikalinos, TA;Contopoulos-Ioannidis, DG
人类遗传学的进展可以帮助我们评估个体的预后，并优化复杂疾病的管理。然而，对同一遗传关联的不同研究有时会有不一致的结果。我们的目的是评估大型研究与小型研究得出不同结论的频率，以及当首次发表的研究结果与后续研究结果不一致时，这种情况是否会更频繁地出现。（579项研究比较）的遗传关联，并测试了遗传效应的大小是否不同，在大型与小型研究。在26项（47%）荟萃分析中研究异质性。在10项（18%）、20项（36%）和21项（38%）荟萃分析中，遗传效应的大小在大型与小型研究中存在显著差异，分别采用秩相关、SE回归和方差倒数回归进行检验。最大规模的研究通常比完整的荟萃分析（包括所有研究）产生更保守的结果（p=0.005）。在14项（26%）荟萃分析中，首次研究中提出的相关性明显强于后续研究。只有在9项（16%）荟萃分析中，遗传相关性显著且重复，没有异质性或偏倚的迹象。在首次与后续差异、大差异与小差异中几乎没有一致性。解释真正的异质性和偏倚可能会影响遗传关联研究的结果。复杂疾病的遗传风险因素应谨慎评估，如果可能的话，使用大规模的证据。
Background Advances in human genetics could help us to assess prognosis on an individual basis and to optimise the management of complex diseases. However, different studies on the same genetic association sometimes have discrepant results. Our aim was to assess how often large studies arrive at different conclusions than smaller studies, and whether this situation arises more frequently when findings of first published studies disagree with those of subsequent research.Methods We examined the results of 55 meta-analyses (579 study comparisons) of genetic associations and tested whether the magnitude of the genetic effect differs in large versus smaller studies.Findings We noted significant between-study heterogeneity in 26 (47%) meta-analyses. The magnitude of the genetic effect differed significantly in large versus smaller studies in ten (18%), 20 (36%), and 21 (38%) meta-analyses with tests of rank correlation, regression on SE, and regression on inverse of variance, respectively. The largest studies generally yielded more conservative results than the complete meta-analyses, which included all studies (p=0.005). In 14 (26%) meta-analyses the proposed association was significantly stronger in the first studies than in subsequent research. Only in nine (16%) meta-analyses was the genetic association significant and replicated without hints of heterogeneity or bias. There was little concordance in first versus subsequent discrepancies, and large versus small discrepancies.Interpretation Genuine heterogeneity and bias could affect the results of genetic association studies. Genetic risk factors for complex diseases should be assessed cautiously and, if possible, using large scale evidence.