EPIC-Norfolk Epigenome-Wide Association Study of Incident Type 2 Diabetes

This EWAS was undertaken in an incident T2DM case-cohort study nested within the EPIC-Norfolk study, a prospective cohort study that recruited 25,639 individuals aged between 40-79 years at baseline in 1993-1997. Incident T2DM cases were ascertained from multiple sources: two follow-up health and lifestyle questionnaires providing self-reported information on doctor-diagnosed diabetes or medications; medications brought to the second clinical exam; and medical record linkage. DNAm intensity was measured using the Illumina HumanMethylation450 array. Bisulfite conversion of DNA was performed using the EZ DNA methylation kit (Zymo Research, Orange, CA, USA). Diabetes DNAm was measured in DNA extracted from whole blood samples collected at baseline. Converted DNA was assayed by PCR (Polymerase Chain Reaction) and gel electrophoresis. Each 96 well DNA sample plate contained two duplicate samples. The average correlation between the duplicate samples was 98%. To identify MVPs associated with incident T2DM, we performed a logistic regression model for each methylation marker with incident T2DM status, adjusted for age, sex, estimated cell counts, and sample plate.

本研究为一项新发2型糖尿病（Type 2 Diabetes Mellitus, T2DM）病例队列研究，嵌套于欧洲癌症与营养前瞻性调查诺福克队列（EPIC-Norfolk）之中，用于开展表观基因组全关联研究（Epigenome-Wide Association Study, EWAS）。EPIC-Norfolk作为前瞻性队列研究，于1993至1997年间招募了25639名基线年龄介于40-79岁的受试者。新发2型糖尿病病例通过多途径确认：两份随访健康与生活方式问卷，用于收集自我报告的医生确诊糖尿病或用药史信息；第二次临床体检时受试者携带的用药记录；以及医疗记录关联数据。DNA甲基化（DNA methylation, DNAm）强度采用Illumina HumanMethylation450芯片进行检测。基因组DNA的亚硫酸氢盐转化实验使用EZ DNA甲基化试剂盒（Zymo Research，美国加利福尼亚州奥兰治市）完成。糖尿病相关DNA甲基化水平的检测，使用的是从基线采集的全血样本中提取的DNA。经亚硫酸氢盐转化的DNA通过聚合酶链式反应（Polymerase Chain Reaction, PCR）与凝胶电泳完成检测。每块96孔DNA样本板包含两份重复样本，重复样本间的平均相关系数达98%。为筛选与新发2型糖尿病相关的甲基化变异位点（Methylation Variable Positions, MVPs），我们针对每个甲基化标记物构建logistic回归模型，以新发2型糖尿病状态为因变量，校正年龄、性别、估算细胞比例及样本板因素。

搜集汇总

背景与挑战

背景概述

该数据集是EPIC-Norfolk队列中针对2型糖尿病发病的表观基因组关联研究（EWAS）数据，发布于2019年。研究基于前瞻性队列设计，涉及25,639名基线年龄40-79岁的参与者，使用Illumina HumanMethylation450阵列测量全血DNA甲基化，并通过逻辑回归分析识别与2型糖尿病发病相关的甲基化变异位点。数据开放获取，适用于表观遗传学和糖尿病研究。