Performance of the log-linear approach to case-parent triad data for assessing maternal genetic associations with offspring disease: Type I error, power, and bias
Performance of the log-linear approach to case-parent triad data for assessing maternal genetic associations with offspring disease: Type I error, power, and bias
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DOI：
10.1093/aje/kwi021
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发表时间：
2005-01-15
影响因子：
5
通讯作者：
Schwartz, SM
中科院分区：
文献类型：
--
作者：
Starr, JR;Hsu, L;Schwartz, SM
母亲遗传变异可作为生物标志物，用于研究澄清婴儿或成人疾病的胎儿决定因素。病例-亲本三联体数据（LCPT）的对数线性方法可用于研究与后代疾病风险相关的母体遗传多态性，但LCPT操作特征仅在有限范围的情况下被报道。作者进行了一项模拟研究，以调查LCPT在不同样本量(n)、高风险等位基因频率(f)和遗传模式的广泛情况下评估母亲与后代疾病风险关联的性能，所有这些都极大地影响了信息类别中三联体的预期数量。对于大多数小于0.5的f值，当遗传为对数加性或显性遗传时，具有200个三元组的LCPT方法允许大约80%的功率来检测有效的、无偏的母体相对风险为2。当遗传为隐性遗传时，对于大多数大于0.35的f都是如此。然而，在这个范围之外，权力和偏见很大程度上取决于遗传模式f和n。基于这些发现，流行病学家可能认为LCPT是评估母亲相对风险的有用方法，除非人们期望非常罕见或相当常见的母亲等位基因会增加后代的疾病风险。
Maternal genetic variation may serve as a biomarker in studies aimed at clarifying fetal determinants of infant or adult disease. The log-linear approach to case-parent triad data (LCPT) can be used to investigate maternal genetic polymorphisms in relation to offspring disease risk, but LCPT operating characteristics have been reported for only a limited range of situations. The authors performed a simulation study to investigate the performance of the LCPT for assessing maternal associations with offspring disease risk over a wide range of scenarios with varying sample sizes (n), high-risk allele frequencies (f ), and modes of inheritance, all of which greatly affect the expected number of triads in informative categories. For most f values less than 0.5, the LCPT approach with 200 triads allowed for approximately 80% power to detect valid, unbiased maternal relative risks of 2 when inheritance was log-additive or dominant. When inheritance was recessive, this was true for most f 's greater than 0.35. Outside of this range, however, power and bias depended greatly on the mode of inheritance, f, and n. On the basis of these findings, epidemiologists may consider the LCPT a useful approach for assessing maternal relative risks unless one expects a very rare or fairly common maternal allele to increase offspring disease risk.