University of Colorado Anschutz Medical Campus, Division of Biomedical Informatics and Personalized Medicine, Aurora, CO, USA.
Colorado School of Public Health, Department of Biostatistics and Informatics, Aurora, CO, USA.
Sci Rep. 2020 Feb 28;10(1):3721. doi: 10.1038/s41598-020-60758-0.
DNA methylation may be involved in development of type 1 diabetes (T1D), but previous epigenome-wide association studies were conducted among cases with clinically diagnosed diabetes. Using multiple pre-disease peripheral blood samples on the Illumina 450 K and EPIC platforms, we investigated longitudinal methylation differences between 87 T1D cases and 87 controls from the prospective Diabetes Autoimmunity Study in the Young (DAISY) cohort. Change in methylation with age differed between cases and controls in 10 regions. Average longitudinal methylation differed between cases and controls at two genomic positions and 28 regions. Some methylation differences were detectable and consistent as early as birth, including before and after the onset of preclinical islet autoimmunity. Results map to transcription factors, other protein coding genes, and non-coding regions of the genome with regulatory potential. The identification of methylation differences that predate islet autoimmunity and clinical diagnosis may suggest a role for epigenetics in T1D pathogenesis; however, functional validation is warranted.
DNA 甲基化可能与 1 型糖尿病（T1D）的发展有关，但之前的全基因组关联研究是在临床诊断为糖尿病的病例中进行的。我们使用 Illumina 450K 和 EPIC 平台上的 87 例 T1D 病例和 87 例对照的多个疾病前外周血样本，在前瞻性的年轻糖尿病自身免疫研究（DAISY）队列中研究了 10 个区域中病例和对照之间的纵向甲基化差异。在 10 个区域中，病例和对照之间的甲基化随年龄的变化不同。在两个基因组位置和 28 个区域，病例和对照之间的平均纵向甲基化存在差异。一些甲基化差异早在出生时就可检测到且一致，包括在临床前胰岛自身免疫之前和之后。结果映射到基因组的转录因子、其他蛋白编码基因和具有调节潜力的非编码区域。在胰岛自身免疫和临床诊断之前发现的甲基化差异可能表明表观遗传学在 T1D 发病机制中的作用；然而，需要进行功能验证。
