Heavner Karyn, Newschaffer Craig, Hertz-Picciotto Irva, Bennett Deborah, Burstyn Igor
Department of Environmental and Occupational Health, Dornsife School of Public Health, Drexel University, Philadelphia, PA 19104, USA.
A.J. Drexel Autism Institute, Dornsife School of Public Health, Drexel University, Philadelphia, PA 19104, USA.
Int J Environ Res Public Health. 2015 Nov 19;12(11):14780-99. doi: 10.3390/ijerph121114780.
We sought to determine the potential effects of pooling on power, false positive rate (FPR), and bias of the estimated associations between hypothetical environmental exposures and dichotomous autism spectrum disorders (ASD) status. Simulated birth cohorts in which ASD outcome was assumed to have been ascertained with uncertainty were created. We investigated the impact on the power of the analysis (using logistic regression) to detect true associations with exposure (X₁) and the FPR for a non-causal correlate of exposure (X₂, r = 0.7) for a dichotomized ASD measure when the pool size, sample size, degree of measurement error variance in exposure, strength of the true association, and shape of the exposure-response curve varied. We found that there was minimal change (bias) in the measures of association for the main effect (X₁). There is some loss of power but there is less chance of detecting a false positive result for pooled compared to individual level models. The number of pools had more effect on the power and FPR than the overall sample size. This study supports the use of pooling to reduce laboratory costs while maintaining statistical efficiency in scenarios similar to the simulated prospective risk-enriched ASD cohort.
我们试图确定合并对功效、假阳性率（FPR）以及假设的环境暴露与二分法自闭症谱系障碍（ASD）状态之间估计关联的偏差的潜在影响。创建了模拟出生队列，其中假设ASD结局的确定存在不确定性。我们研究了在合并样本量、总样本量、暴露测量误差方差程度、真实关联强度以及暴露-反应曲线形状变化时，对分析功效（使用逻辑回归）检测与暴露（X₁）的真实关联以及二分法ASD测量中暴露的非因果相关因素（X₂，r = 0.7）的FPR的影响。我们发现主要效应（X₁）的关联测量变化极小（偏差）。与个体水平模型相比，合并会导致一定的功效损失，但检测到假阳性结果的可能性较小。合并样本的数量对功效和FPR的影响大于总样本量。本研究支持在类似于模拟的前瞻性风险富集ASD队列的情况下，使用合并来降低实验室成本，同时保持统计效率。
