Am J Epidemiol. 2016 Nov 15;184(10):779-786. doi: 10.1093/aje/kww093.
Natural acquisition of small amounts of foreign cells or DNA, referred to as microchimerism, occurs primarily through maternal-fetal exchange during pregnancy. Microchimerism can persist long-term and has been associated with both beneficial and adverse human health outcomes. Quantitative microchimerism data present challenges for statistical analysis, including a skewed distribution, excess zero values, and occasional large values. Methods for comparing microchimerism levels across groups while controlling for covariates are not well established. We compared statistical models for quantitative microchimerism values, applied to simulated data sets and 2 observed data sets, to make recommendations for analytic practice. Modeling the level of quantitative microchimerism as a rate via Poisson or negative binomial model with the rate of detection defined as a count of microchimerism genome equivalents per total cell equivalents tested utilizes all available data and facilitates a comparison of rates between groups. We found that both the marginalized zero-inflated Poisson model and the negative binomial model can provide unbiased and consistent estimates of the overall association of exposure or study group with microchimerism detection rates. The negative binomial model remains the more accessible of these 2 approaches; thus, we conclude that the negative binomial model may be most appropriate for analyzing quantitative microchimerism data.
自然获取少量的外来细胞或 DNA，称为微嵌合体，主要发生在妊娠期间的母婴交换过程中。微嵌合体可以长期存在，并与人类健康的有益和不利结果都有关联。定量微嵌合体数据对统计分析提出了挑战，包括偏态分布、过多的零值和偶尔的大值。目前还没有很好的方法可以在控制协变量的情况下比较组间的微嵌合体水平。我们比较了定量微嵌合体值的统计模型，将其应用于模拟数据集和 2 个观察数据集，为分析实践提出建议。通过泊松或负二项式模型将定量微嵌合体水平建模为速率，其中检测速率定义为检测到的微嵌合体基因组当量与测试的总细胞当量之比，可利用所有可用数据，并促进组间速率的比较。我们发现，边缘化零膨胀泊松模型和负二项式模型都可以提供无偏且一致的估计，以说明暴露或研究组与微嵌合体检测率之间的总体关联。负二项式模型仍然是这两种方法中更容易使用的方法；因此，我们得出结论，负二项式模型可能最适合分析定量微嵌合体数据。
