未经证实:2型糖尿病(T2D)是一种与多种合并症相关的常见慢性疾病。
未经证实:这项研究调查了T2D的风险是否随基因预测的胰岛素(INS)而变化,胰岛素受体(INS-R),或胰岛素样生长因子1受体(IGF-1R)在孟德尔随机(MR)研究中使用遗传变异。
UNASSIGNED:使用来自2个全基因组关联研究(GWAS)的汇总统计数据进行了2个样本的MR研究。暴露的遗传预测因子(INS,INS-R,和IGF-1R)从英国INTERVAL献血随机对照试验的公开蛋白质组学GWAS中获得。对于T2D,这项研究利用了DIAbetes跨族裔协会研究(DIAMANTE)联盟的元分析。估计的INS协会,INS-R,与T2D的IGF-1R蛋白强烈基于独立的单核苷酸多态性(SNP)(P<5×10-6)预测每次暴露。这些SNP被应用于来自DIAMANTE病例(n=74,124)和欧洲血统的对照(n=824,006)研究的与T2D的公开遗传关联。使用具有乘法随机效应的逆方差加权对SNP特异性Wald估计值进行荟萃分析。使用加权中位数(WM)和MR-Egger进行敏感性分析。
未经评估:INS-R(基于13个SNP)与T2D的较低风险相关(OR:每个效应大小为0.95;95%CI:0.92,0.98;P=0.001),来自WM和MR-Egger的类似估计。胰岛素(8个SNPs)和IGF-1R(10个SNPs)与T2D无关。然而,INS-R的1个SNP来自ABO血型基因。
UNASSIGNED:该研究与INS-R与T2D的因果关系保护相关一致。红细胞中的INS-R调节糖酵解,因此可能影响其功能和完整性。然而,不能排除通过血型ABO基因的多效性效应.INS-R可以是通过重新利用现有治疗剂或以其他方式降低T2D风险的干预的靶标。
UNASSIGNED: Type 2 diabetes (T2D) is a prevalent chronic disease associated with several comorbidities.
UNASSIGNED: This study investigated whether the risk of T2D varied with genetically predicted insulin (INS), insulin receptor (INS-R), or insulin-like growth factor 1 receptor (IGF-1R) using genetic variants in a Mendelian randomization (MR) study.
UNASSIGNED: A 2-sample MR study was conducted using summary statistics from 2 genome-wide association studies (GWASs). Genetic predictors of the exposures (INS, INS-R, and IGF-1R) were obtained from a publicly available proteomics GWAS of the INTERVAL randomized controlled trial of blood donation in the United Kingdom. For T2D, the study leveraged the DIAbetes Meta-ANalysis of Trans-Ethnic association studies (DIAMANTE) consortium. The estimated associations of INS, INS-R, and IGF-1R proteins with T2D were based on independent single nucleotide polymorphisms (SNPs) strongly (P < 5 × 10-6) predicting each exposure. These SNPs were applied to publicly available genetic associations with T2D from the DIAMANTE case (n = 74,124) and control (n = 824,006) study of people of European descent. SNP-specific Wald estimates were meta-analyzed using inverse variance weighting with multiplicative random effects. Sensitivity analysis was conducted using the weighted median (WM) and MR-Egger.
UNASSIGNED: INS-R (based on 13 SNPs) was associated with a lower risk of T2D (OR: 0.95 per effect size; 95% CI: 0.92, 0.98; P = 0.001), with similar estimates from the WM and MR-Egger. Insulin (8 SNPs) and IGF-1R (10 SNPs) were not associated with T2D. However, 1 of the SNPs for INS-R was from the ABO blood group gene.
UNASSIGNED: This study is consistent with a causally protective association of the INS-R with T2D. INS-R in RBCs regulates glycolysis and thus may affect their functionality and integrity. However, a pleiotropic effect via the blood group ABO gene cannot be excluded. The INS-R may be a target for intervention by repurposing existing therapeutics or otherwise to reduce the risk of T2D.