Additional file 2 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

Additional file 2: Table S2. Epigenome-wide association study (EWAS) of metabolic measures. Presented are CpG site-metabolic measurement pairs statistically significantly associated in the KORA F4 discovery study. Results for the discovery analysis in KORA (“KORA”), the sensitivity analysis in KORA (“_KORA_Sens”), LOLIPOP (“_LOLIPOP”), NFBC1966 (“_NFBC”), and Young Finns (“_YFS”) studies, as well as the results for the meta-analysis (“_MA”) of these three replication studies, are presented. The scaled coefficients of the sensitivity analysis in KORA (“Coef_KORA_scaled”, i.e., both the log-transformed metabolite measure and methylation beta value were z-transformed prior to analysis) are also presented. The coefficients and p values for the discovery KORA analysis were calculated based on the results of 10 MICE imputed datasets and combined using the commands pool.scalar and micombine.chisquare, from the R packages mice and micetools, respectively. Discovery (KORA F4) significance based on p value < 4.73e−10; meta-analysis significance based on p value < 1.80e−4 (based on 274 pairs tested for replication). Gene, CHR, and Pos: gene, chromosome, and position annotation for the CpG site taken from the Illumina 450 K annotation file; Coef: coefficient of the CpG site from the regression analysis; SE: standard error of the coefficient; P: p value for the regression coefficient; N: number of observations; P_Bonf: Bonferroni-corrected p value for the given analysis; Explained_variance_KORA: percentage of explained variance of the log-transformed metabolic measure by the CpG; Stat_Sig_MA: statistically significant in the meta-analysis of the three replication studies. Unless otherwise specified, all coefficients are change in natural log-transformed metabolite measurement unit (as given in Additional file 1: Table S1) per unit increase in methylation (beta value on 0–1 scale).

附加文件2：表S2。代谢指标的表观全基因组关联研究（Epigenome-wide association study, EWAS）。本文展示了KORA F4发现研究中经统计学检验具有显著关联的CpG位点-代谢指标配对。本次展示的结果涵盖：KORA队列的发现分析（标注为"KORA"）、KORA队列的敏感性分析（标注为"_KORA_Sens"）、LOLPOP研究（标注为"_LOLIPOP"）、NFBC1966研究（标注为"_NFBC"）与青年芬兰人研究（标注为"_YFS"）的分析结果，以及上述三项重复研究的元分析（meta-analysis，标注为"_MA"）结果。同时还提供了KORA队列敏感性分析的标准化系数（Coef_KORA_scaled，即分析前已对对数转换后的代谢指标与甲基化β值均进行了Z变换）。KORA发现分析的系数与P值基于10个MICE插补数据集计算得到，并分别通过R包mice中的pool.scalar命令与micetools中的micombine.chisquare命令进行合并。KORA F4发现阶段的统计学显著性阈值为P值<4.73×10^−10；元分析的统计学显著性阈值为P值<1.80×10^−4（针对274个待重复检验的配对）。各字段含义如下：Gene、CHR及Pos分别为取自Illumina 450K注释文件的CpG位点对应的基因、染色体与位置注释；Coef为回归分析中CpG位点的回归系数；SE为该系数的标准误；P为回归系数对应的P值；N为观测样本量；P_Bonf为对应分析的Bonferroni校正P值；Explained_variance_KORA为CpG位点对对数转换后代谢指标的解释方差百分比；Stat_Sig_MA表示该位点在三项重复研究的元分析中具有统计学显著性。除非另有说明，所有系数均表示甲基化水平（β值取值范围为0~1）每增加1个单位时，自然对数转换后的代谢指标的变化量（具体单位详见附加文件1：表S1）。