We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI_95% = [0.62–0.68], p = 8.3 × 10⁻²²). The maximum AUC achieved was 0.69 (CI_95% = [0.66–0.71], p = 4.3 × 10⁻³⁴) when cell-type proportion was included in the predictor.

我们使用来自全血的Illumina 450K数据对澳大利亚的肌萎缩性侧索硬化症（ALS）病例对照队列（782例和613对照）进行了DNA甲基化关联分析。分析使用了OSCA软件中实现的混合线性模型。与在荷兰独立队列中复制的对照相比，我们发现案例中的中性粒细胞比例要高得多（1159例和637个对照）。在仿真中已经显示了OSCA MOMENT线性混合模型，可以最好地说明混杂因素。当结合甲基化谱得分时，MOMENT鉴定出的25个最相关的探针对荷兰样品中的病例对照状态进行了显着分类（曲线下面积，AUC = 0.65，CI _95％  = [0.62-0.68]，p  = 8.3） ×10⁻²²）。当预测因子中包含细胞类型比例时 ，获得的最大AUC为0.69（CI _95％ = [0.66-0.71]，p  = 4.3×10 ^-34）。