Estimation of odds ratios of genetic variants for the secondary phenotypes associated with primary diseases.
Estimation of odds ratios of genetic variants for the secondary phenotypes associated with primary diseases.
复制标题
DOI：
10.1002/gepi.20568
复制
发表时间：
2011-04
影响因子：
2.1
通讯作者：
Shete, Sanjay
中科院分区：
文献类型：
--
作者：
Wang, Jian;Shete, Sanjay
关键词：
对二元疾病的遗传关联研究是作为病例对照研究设计的：病例是受原发疾病影响的人，对照者没有该疾病。在收集病例对照时，还收集了有关继发性表型的信息。继发表型与遗传变异的关联研究近年来引起了人们极大的兴趣。为了研究继发性表型，研究人员使用标准回归方法，其中具有继发性表型的个体被编码为病例，而没有继发性表型的个体被编码为对照。然而，在病例对照研究中使用继发表型作为结果变量可能导致遗传变异的优势比（ORs）估计有偏倚。继发表型与原发疾病相关；因此，有或没有继发性表型的个体不按照病例对照研究的原则取样。在这篇文章中，我们证明了这样的分析将导致对OR的偏倚估计，并提出了新的方法来提供与继发表型相关的遗传变异更准确的OR估计，无论是不匹配的还是频率匹配的（相对于继发表型）病例对照研究。我们还提出了一种自举方法来估计修正后的ORs的经验置信区间。通过模拟研究和分析肺癌数据中与吸烟数量相关的单核苷酸多态性，我们将我们的新方法与标准逻辑回归和扩展版本的反概率抽样加权回归进行了比较。所提出的方法提供了更准确的真实OR估计。
Genetic association studies for binary diseases are designed as case-control studies: the cases are those affected with the primary disease and the controls are free of the disease. At the time of case-control collection, information about secondary phenotypes is also collected. Association studies of secondary phenotype and genetic variants have received a great deal of interest recently. To study the secondary phenotypes, investigators use standard regression approaches, where individuals with secondary phenotypes are coded as cases and those without secondary phenotypes are coded as controls. However, using the secondary phenotype as an outcome variable in a case-control study might lead to a biased estimate of odds ratios (ORs) for genetic variants. The secondary phenotype is associated with the primary disease; therefore, individuals with and without the secondary phenotype are not sampled following the principles of a case-control study. In this article, we demonstrate that such analyses will lead to a biased estimate of OR and propose new approaches to provide more accurate OR estimates of genetic variants associated with the secondary phenotype for both unmatched and frequency-matched (with respect to the secondary phenotype) case-control studies. We also propose a bootstrapping method to estimate the empirical confidence intervals for the corrected ORs. Using simulation studies and analysis of lung cancer data for single-nucleotide polymorphism associated with smoking quantity, we compared our new approaches to standard logistic regression and to an extended version of the inverse-probability-of-sampling-weighted regression. The proposed approaches provide more accurate estimation of the true OR.
登录
查看更多内容
影响因子：
30.8
作者：
He, Chunyan;Kraft, Peter;Chen, Constance;Buring, Julie E.;Pare, Guillaume;Hankinson, Susan E.;Chanock, Stephen J.;Ridker, Paul M.;Hunter, David J.;Chasman, Daniel I.
通讯作者：
Chasman, Daniel I.
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.
影响因子：
2.1
作者：
Monsees, Genevieve M.;Tamimi, Rulla M.;Kraft, Peter
通讯作者：
Kraft, Peter
影响因子：
2.1
作者：
Lin, D. Y.;Zeng, D.
通讯作者：
Zeng, D.
影响因子：
5.8
作者：
Halekoh, U;Hojsgaard, S;Yan, J
通讯作者：
Yan, J