Cross-Ancestry DNA Methylation Marks of Insulin Resistance in Pregnancy: An Integrative Epigenome-Wide Association Study.
Cross-Ancestry DNA Methylation Marks of Insulin Resistance in Pregnancy: An Integrative Epigenome-Wide Association Study.
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作者：
虽然有一些关于胰岛素抵抗的表观基因组关联研究，但大多数作者没有重复他们的发现，而且大多数集中在欧洲血统的人群中，限制了推广。在孕期表观遗传学(EPIPREG；n=294名欧洲人和162名南亚人)研究中，我们对孕妇外周血白细胞中的胰岛素抵抗进行了表观遗传学研究，并在布拉德福德出生(n=879；430名欧洲人和449名南亚人)、甲基表观基因组网络协会(MENA)(n=320)和波特尼亚(n=56)队列中进行了复制。在EPIPREG中，我们发现了6个与胰岛素抵抗呈负相关的CpG位点，其中5个在独立队列中复制(TXNIP中的cg02988288、cg19693031和cg26974062；SLC7A11中的cg06690548；以及ZSCAN26中的cg04861640)。从EPIPREG的甲基化数量性状座位分析中，我们发现了与所有五个复制的交叉祖先CpG位点相关的基因变异，这些基因变异与几种心脏代谢表型有关。中介分析表明，这些基因变异通过DNA甲基化来调节胰岛素抵抗。综上所述，我们的交叉祖先发现了五个与较低胰岛素抵抗相关的CpG位点。
Although there are some epigenome-wide association studies (EWAS) of insulin resistance, for most of them authors did not replicate their findings, and most are focused on populations of European ancestry, limiting the generalizability. In the Epigenetics in Pregnancy (EPIPREG; n = 294 Europeans and 162 South Asians) study, we conducted an EWAS of insulin resistance in maternal peripheral blood leukocytes, with replication in the Born in Bradford (n = 879; n = 430 Europeans and 449 South Asians), Methyl Epigenome Network Association (MENA) (n = 320), and Botnia (n = 56) cohorts. In EPIPREG, we identified six CpG sites inversely associated with insulin resistance across ancestry, of which five were replicated in independent cohorts (cg02988288, cg19693031, and cg26974062 in TXNIP; cg06690548 in SLC7A11; and cg04861640 in ZSCAN26). From methylation quantitative trait loci analysis in EPIPREG, we identified gene variants related to all five replicated cross-ancestry CpG sites, which were associated with several cardiometabolic phenotypes. Mediation analyses suggested that the gene variants regulate insulin resistance through DNA methylation. To conclude, our cross-ancestry EWAS identified five CpG sites related to lower insulin resistance.
影响因子：
3.5
作者：
Hoffmann A;Ziller M;Spengler D
通讯作者：
Spengler D