BACKGROUND Type 2 diabetes (T2D) results from a complex interplay between genetics and the environment. Several epigenome-wide association studies (EWAS) have found DNA methylation loci associated with T2D in European populations. However, data from African populations are lacking. We undertook the first EWAS for T2D among sub-Saharan Africans, aiming at identifying ubiquitous and novel DNA methylation loci associated with T2D. METHODS The Illumina 450k DNA-methylation array was used on whole blood samples of 713 Ghanaian participants (256 with T2D, 457 controls) from the cross-sectional Research on Obesity and Diabetes among African Migrants (RODAM) study. Differentially methylated positions (DMPs) for T2D and HbA1c were identified through linear regression analysis adjusted for age, sex, estimated cell counts, hybridization batch, array position and body mass index (BMI). We also did a candidate analysis of previously reported EWAS loci for T2D in non-African populations, identified through a systematic literature search. RESULTS Four DMPs [cg19693031 (TXNIP), cg04816311 (C7orf50), cg00574958 (CPT1A), cg07988171 (TPM4)] were associated with T2D after correction for inflation by possible systematic biases. The most strongly associated DMP-cg19693031, TXNIP (P = 2.6E-19) -showed hypomethylation in T2D cases compared with controls. Two out of the four DMPs [cg19693031 (TXNIP), cg04816311 (C7orf50)] remained associated with T2D after adjustment for BMI, and one locus [cg07988171 (TPM4)] that has not been reported previously. CONCLUSIONS In this first EWAS for T2D in sub-Saharan Africans, we have identified four DMPs at epigenome-wide level, one of which is novel. These findings provide insight into the epigenetic loci that underlie the burden of T2D in sub-Saharan Africans.

中文翻译：

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撒哈拉以南非洲个体全血与 2 型糖尿病的表观基因组关联研究：RODAM 研究的结果。


背景技术 2 型糖尿病 (T2D) 是遗传与环境之间复杂相互作用的结果。几项全表观基因组关联研究 (EWAS) 发现了欧洲人群中与 T2D 相关的 DNA 甲基化位点。然而，缺乏来自非洲人口的数据。我们在撒哈拉以南非洲地区开展了首次针对 T2D 的 EWAS，旨在识别与 T2D 相关的普遍存在的新型 DNA 甲基化位点。方法 Illumina 450k DNA 甲基化芯片用于非洲移民肥胖和糖尿病横断面研究 (RODAM) 研究中 713 名加纳参与者（256 名患有 T2D，457 名对照）的全血样本。通过根据年龄、性别、估计细胞计数、杂交批次、阵列位置和体重指数 (BMI) 进行调整的线性回归分析，确定了 T2D 和 HbA1c 的差异甲基化位置 (DMP)。我们还对之前报道的非非洲人群中 T2D 的 EWAS 基因座进行了候选分析，这些基因座是通过系统文献检索确定的。结果 四个 DMP [cg19693031 (TXNIP)、cg04816311 (C7orf50)、cg00574958 (CPT1A)、cg07988171 (TPM4)] 在通过可能的系统偏差校正通货膨胀后与 T2D 相关。与对照相比，相关性最强的 DMP-cg19693031、TXNIP (P = 2.6E-19) 在 T2D 病例中表现出低甲基化。调整 BMI 后，四个 DMP 中的两个 [cg19693031 (TXNIP)、cg04816311 (C7orf50)] 仍与 T2D 相关，并且一个位点 [cg07988171 (TPM4)] 之前尚未报道。结论 在第一个撒哈拉以南非洲人 T2D 的 EWAS 中，我们在表观基因组水平上鉴定了四种 DMP，其中一种是新颖的。 这些发现提供了对撒哈拉以南非洲人 T2D 负担背后的表观遗传位点的深入了解。