Analytical approaches to detect maternal/fetal genotype incompatibilities that increase risk of pre-eclampsia.

Analytical approaches to detect maternal/fetal genotype incompatibilities that increase risk of pre-eclampsia.
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分析方法检测出孕产妇/胎儿基因型不兼容,从而增加了先兆子痫的风险。

DOI:
10.1186/1471-2350-9-60
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发表时间:
2008-07-03
影响因子:
--
通讯作者:
Goddard, Katrina A. B.
Goddard, Katrina A. B.
中科院分区:
医学4区
文献类型:
--
作者:
Parimi, Neeta;Tromp, Gerard;Kuivaniemi, Helena;Nien, Jyh Kae;Gomez, Ricardo;Romero, Roberto;Goddard, Katrina A. B.

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母体与胎儿不相容的基因型之间在子宫内的相互作用是妊娠相关疾病(如子痫前期)发病或进展的一种潜在机制。然而,评估母体/后代不相容基因型组合的最佳分析方法和研究设计尚不明确。 通过模拟,我们评估了两种分析方法中母体/后代不相容基因型模型的I型错误和效能:用于病例 - 对照母体/后代对的逻辑回归以及用于病例 - 父母三联体的对数线性回归。我们根据模拟研究的结果,使用最优分析方法评估了一个包含患有和未患子痫前期的母体/后代对的真实数据集的不相容性效应。 我们确定了一种单一的编码方案用于不相容性效应,无论不相容性效应的真实潜在模型如何,该方案与所评估的所有替代分析模型相比,效能相同或更高。此外,当遗传力较低时,对数线性回归比逻辑回归更有效能,并且对母体或胎儿效应的调整更稳健。对于子痫前期数据,该分析揭示了三个可能具有不相容性效应的基因,即淋巴毒素α(LTA)、血管性血友病因子(VWF)和IV型胶原蛋白α2链(COL4A2)。 对于妊娠并发症(如子痫前期),应评估不相容性模型,因为两个个体的基因型可能与疾病的发生有关。
In utero interactions between incompatible maternal and fetal genotypes are a potential mechanism for the onset or progression of pregnancy related diseases such as pre-eclampsia (PE). However, the optimal analytical approach and study design for evaluating incompatible maternal/offspring genotype combinations is unclear. Using simulation, we estimated the type I error and power of incompatible maternal/offspring genotype models for two analytical approaches: logistic regression used with case-control mother/offspring pairs and the log-linear regression used with case-parent triads. We evaluated a real dataset consisting of maternal/offspring pairs with and without PE for incompatibility effects using the optimal analysis based on the results of the simulation study. We identified a single coding scheme for the incompatibility effect that was equally or more powerful than all of the alternative analysis models evaluated, regardless of the true underlying model for the incompatibility effect. In addition, the log-linear regression was more powerful than the logistic regression when the heritability was low, and more robust to adjustment for maternal or fetal effects. For the PE data, this analysis revealed three genes, lymphotoxin alpha (LTA), von Willebrand factor (VWF), and alpha 2 chain of type IV collagen (COL4A2) with possible incompatibility effects. The incompatibility model should be evaluated for complications of pregnancy, such as PE, where the genotypes of two individuals may contribute to the presence of disease.
DOI: 10.1093/molehr/gah035
发表时间: 2004-04-01
影响因子: 4
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期刊: BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY
影响因子: --
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