Family-based versus unrelated case-control designs for genetic associations.
Family-based versus unrelated case-control designs for genetic associations.
复制标题
DOI：
10.1371/journal.pgen.0020123
复制
发表时间：
2006-08
期刊：
影响因子：
4.5
通讯作者：
Ioannidis JP
中科院分区：
文献类型：
--
作者：
Evangelou E;Trikalinos TA;Salanti G;Ioannidis JP
最简单和最常用的遗传关联方法是对无关人群的病例对照研究设计。这种设计易受人群分层的影响。这个问题在以家庭为基础的研究中得到了解决，但通常很难积累足够大的具有良好特征的家庭样本。我们解决了经验是否两种设计提供了类似的估计，在93项调查，其中既不相关的病例对照和家庭为基础的设计已被采用。两种设计之间的估计比值比仅在四种情况下（4%）超出了偶然性。汇总相对比值比（ROR）（从不相关病例对照和基于家族的研究中获得的比值比）接近1（0.96 [95%置信区间，0.91-1.01]）。研究间的ROR无异质性（异质性超出机会I2 = 0%）。两种设计的结果是否具有名义上的统计学显著性（p < 0.05）的差异很常见（相反的分类率分别为14%和17%）;这主要反映了功效的差异。在不同的亚组分析中，结论基本相似。不相关的病例对照和基于家族的设计给出了总体相似的关联估计。我们不能排除罕见的大偏差或常见的小偏差。不同类型的设计用于评估复杂疾病的遗传关联。最广泛使用的是不相关人群的病例对照研究和基于家庭的设计。每一种都有其优点和缺点。本文使用荟萃分析方法比较了两种类型设计的估计值，即系统选择数据并对许多研究的结果进行定量合成。作者检查了93个协会，其中采用了不相关的病例对照和以家庭为基础的设计。两种设计给出了总体相似的关联估计，并且在考虑了可能在理论上影响两种设计之间一致程度的各种设计特征的亚组分析中，结论非常相似。未观察到研究间的异质性。因此，不存在与一种或另一种设计的探测相关性的一致高估或低估模式。然而，不能排除两种设计之间可能出现罕见的大差异或常见的小差异的可能性。
The most simple and commonly used approach for genetic associations is the case-control study design of unrelated people. This design is susceptible to population stratification. This problem is obviated in family-based studies, but it is usually difficult to accumulate large enough samples of well-characterized families. We addressed empirically whether the two designs give similar estimates of association in 93 investigations where both unrelated case-control and family-based designs had been employed. Estimated odds ratios differed beyond chance between the two designs in only four instances (4%). The summary relative odds ratio (ROR) (the ratio of odds ratios obtained from unrelated case-control and family-based studies) was close to unity (0.96 [95% confidence interval, 0.91–1.01]). There was no heterogeneity in the ROR across studies (amount of heterogeneity beyond chance I2 = 0%). Differences on whether results were nominally statistically significant (p < 0.05) or not with the two designs were common (opposite classification rates 14% and 17%); this reflected largely differences in power. Conclusions were largely similar in diverse subgroup analyses. Unrelated case-control and family-based designs give overall similar estimates of association. We cannot rule out rare large biases or common small biases. Different types of designs are used for the assessment of genetic associations for complex diseases. Case-control studies of unrelated people and family-based designs are the most widely used. Each has its advantages and disadvantages. This paper compares the estimates of the two types of design using a meta-analytic approach, i.e. a systematic selection of data and quantitative synthesis of results across many studies. The authors examined 93 associations where both unrelated case-control and family-based designs had been employed. Both designs gave overall similar estimates of association and the conclusions were very similar in subgroup analyses that considered various design features that might affect in theory the degree of agreement between the two designs. No heterogeneity between studies was observed. Hence, there was no consistent pattern of over-estimation or under-estimation of the probed association with one or the other design. However, one cannot exclude the possibility that rare large differences or common small differences may occur between the two designs.
登录
查看更多内容
影响因子：
11
作者：
Daly, G;Hawi, Z;Gill, M
通讯作者：
Gill, M
影响因子：
9.8
作者：
Mirza, MM;Fisher, SA;Mathew, CG
通讯作者：
Mathew, CG
影响因子：
168.9
作者：
Hattersley, AT;McCarthy, MI
通讯作者：
McCarthy, MI
影响因子：
168.9
作者：
Ioannidis, JPA;Trikalinos, TA;Contopoulos-Ioannidis, DG
通讯作者：
Contopoulos-Ioannidis, DG
影响因子：
30.8
作者：
Clayton, DG;Walker, NM;Todd, JA
通讯作者：
Todd, JA