Berg F, Köper E, Limberg A S, Mattonet K, Budeus B, Kumsta R, Hummel E M, Moser D A
Department of Genetic Psychology, Faculty of Psychology, Ruhr-University Bochum, Bochum, Germany.
Institute of Cell Biology, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
Epigenomics. 2025 Apr;17(6):389-396. doi: 10.1080/17501911.2025.2479423. Epub 2025 Mar 18.
Epidemiological studies of DNA methylation often use buccal swabs, which contain mixtures of cell types, but no low-cost methods exist for statistical correction in candidate gene studies using targeted bisulfite sequencing. This study aims to address this gap by estimating the proportion of buccal epithelial cells in swab and mouthwash samples.
MATERIALS & METHODS: We applied a recently described and smoothly to implement method for estimating the proportion of buccal epithelial cells in buccal swab and mouthwash samples using targeted bisulfite sequencing. Additionally, we investigated the methylation of (), a marker for cell type-specific methylation, following psychosocial and physical stress.
The proposed estimation method showed strong correlation with the EpiDISH algorithm and effectively controlled for cellular heterogeneity. Over 90% of the variance in methylation was explained by including the epithelial cell proportion in the model.
Our findings provide a solution for controlling cellular heterogeneity in buccal swab and mouthwash DNA methylation studies. This method is particularly relevant for candidate gene studies in clinical settings, but future work should refine it for more detailed analyses of cell type proportions to improve precision.
DNA甲基化的流行病学研究通常使用颊拭子，其包含多种细胞类型的混合物，但在使用靶向亚硫酸氢盐测序的候选基因研究中，不存在用于统计校正的低成本方法。本研究旨在通过估计拭子和漱口水样本中颊上皮细胞的比例来填补这一空白。
我们应用了一种最近描述的、易于实施的方法，该方法使用靶向亚硫酸氢盐测序来估计颊拭子和漱口水样本中颊上皮细胞的比例。此外，我们研究了心理社会和身体应激后细胞类型特异性甲基化标记物（）的甲基化情况。
所提出的估计方法与EpiDISH算法显示出强相关性，并有效地控制了细胞异质性。通过在模型中纳入上皮细胞比例，可解释甲基化中超过90%的方差。
我们的研究结果为控制颊拭子和漱口水DNA甲基化研究中的细胞异质性提供了解决方案。该方法在临床环境中的候选基因研究中尤为相关，但未来的工作应进一步完善它，以便更详细地分析细胞类型比例，提高精度。
