DNA methylation of blood cells is associated with prevalent type 2 diabetes in a meta-analysis of four European cohorts.
DNA methylation of blood cells is associated with prevalent type 2 diabetes in a meta-analysis of four European cohorts.
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DOI：
10.1186/s13148-021-01027-3
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发表时间：
2021-02-23
影响因子：
5.7
通讯作者：
Elliott HR
中科院分区：
文献类型：
--
作者：
Juvinao-Quintero DL;Marioni RE;Ochoa-Rosales C;Russ TC;Deary IJ;van Meurs JBJ;Voortman T;Hivert MF;Sharp GC;Relton CL;Elliott HR
2型糖尿病（T2 D）是一种异质性疾病，众所周知的遗传和环境风险因素有助于其患病率。与DNA甲基化（DNAm）变化相关的表观遗传机制也可能导致T2 D风险，但需要更大规模的研究来发现新的标志物，并确认现有的标志物。我们使用外周血DNAm对四项欧洲研究中进行的T2 D流行的个体表观全基因组关联研究（EWAS）进行了大型荟萃分析。根据荟萃分析结果，还进行了差异甲基化区域（DMR）的分析。我们在欧洲人中发现了三个与流行T2 D相关的新CpG，分别位于cg 00144180（HDAC 4）、cg 16765088（靠近SYNM）和cg 24704287（靠近MIR 23 A），并证实了先前发现的三个CpG（定位于TXNIP、ABCG 1和CPT 1A）。我们还确定了77例T2 D相关DMR，其中大多数在T2 D病例中与对照组相比是低甲基化的。在ALSPAC中无糖尿病参与者的校正回归中，我们发现在meta-EWAS中鉴定的所有六个CpG都与白色细胞类型相关。我们估计，这6个CpG捕获了T2 D变异的11%，这与仅包括BMI、性别、年龄和吸烟等常见风险因素的模型解释的变异相似（R2 = 10.6%）。这项研究确定了欧洲人与T2 D相关的新基因座。我们还证明了相同的基因座与其他性状的关联。未来的研究应该调查我们的研究结果是否在非欧洲人群中具有普遍性，以及这些表观遗传标记在T2 D病因学或确定T2 D长期后果中的潜在作用。
Type 2 diabetes (T2D) is a heterogeneous disease with well-known genetic and environmental risk factors contributing to its prevalence. Epigenetic mechanisms related to changes in DNA methylation (DNAm), may also contribute to T2D risk, but larger studies are required to discover novel markers, and to confirm existing ones. We performed a large meta-analysis of individual epigenome-wide association studies (EWAS) of prevalent T2D conducted in four European studies using peripheral blood DNAm. Analysis of differentially methylated regions (DMR) was also undertaken, based on the meta-analysis results. We found three novel CpGs associated with prevalent T2D in Europeans at cg00144180 (HDAC4), cg16765088 (near SYNM) and cg24704287 (near MIR23A) and confirmed three CpGs previously identified (mapping to TXNIP, ABCG1 and CPT1A). We also identified 77 T2D associated DMRs, most of them hypomethylated in T2D cases versus controls. In adjusted regressions among diabetic-free participants in ALSPAC, we found that all six CpGs identified in the meta-EWAS were associated with white cell-types. We estimated that these six CpGs captured 11% of the variation in T2D, which was similar to the variation explained by the model including only the common risk factors of BMI, sex, age and smoking (R2 = 10.6%). This study identifies novel loci associated with T2D in Europeans. We also demonstrate associations of the same loci with other traits. Future studies should investigate if our findings are generalizable in non-European populations, and potential roles of these epigenetic markers in T2D etiology or in determining long term consequences of T2D.
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影响因子：
5.7
作者：
Arathimos R;Suderman M;Sharp GC;Burrows K;Granell R;Tilling K;Gaunt TR;Henderson J;Ring S;Richmond RC;Relton CL
通讯作者：
Relton CL
影响因子：
4.4
作者：
Bonder MJ;Kasela S;Kals M;Tamm R;Lokk K;Barragan I;Buurman WA;Deelen P;Greve JW;Ivanov M;Rensen SS;van Vliet-Ostaptchouk JV;Wolfs MG;Fu J;Hofker MH;Wijmenga C;Zhernakova A;Ingelman-Sundberg M;Franke L;Milani L
通讯作者：
Milani L
影响因子：
4.1
作者：
Deary IJ;Gow AJ;Taylor MD;Corley J;Brett C;Wilson V;Campbell H;Whalley LJ;Visscher PM;Porteous DJ;Starr JM
通讯作者：
Starr JM
影响因子：
16.6
作者：
Huan, Tianxiao;Joehanes, Roby;Leyy, Daniel
通讯作者：
Leyy, Daniel
影响因子：
12.3
作者：
Gaunt TR;Shihab HA;Hemani G;Min JL;Woodward G;Lyttleton O;Zheng J;Duggirala A;McArdle WL;Ho K;Ring SM;Evans DM;Davey Smith G;Relton CL
通讯作者：
Relton CL