Genome-wide association studies (GWASs) have identified hundreds of single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D) and coronary artery disease (CAD), respectively. Nevertheless, these studies were generally performed for single-trait/disease and failed to assess the pleiotropic role of the identified variants. To identify novel functional loci and the pleiotropic relationship between CAD and T2D, the targeted cFDR analysis on CpG-SNPs was performed by integrating two independent large and multi-centered GWASs with summary statistics of T2D (26,676 cases and 132,532 controls) and CAD (60,801 cases and 123,504 controls). Applying the cFDR significance threshold of 0.05, we observed a pleiotropic enrichment between T2D and CAD by incorporating pleiotropic effects into a conditional analysis framework. We identified 79 novel CpG-SNPs for T2D, 61 novel CpG-SNPs for CAD, and 18 novel pleiotropic loci for both traits. Among these novel CpG-SNPs, 33 of them were annotated as methylation quantitative trait locus (meQTL) in whole blood, and ten of them showed expression QTL (eQTL), meQTL, and metabolic QTL (metaQTL) effects simultaneously. To the best of our knowledge, we performed the first targeted cFDR analysis on CpG-SNPs, and our findings provided novel insights into the shared biological mechanisms and overlapped genetic heritability between T2D and CAD.

中文翻译：

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鉴定与 2 型糖尿病和冠状动脉疾病相关的新型功能性 CpG-SNP。

全基因组关联研究 (GWAS) 已经确定了数百个分别与 2 型糖尿病 (T2D) 和冠状动脉疾病 (CAD) 相关的单核苷酸多态性 (SNP)。然而，这些研究通常是针对单一性状/疾病进行的，未能评估已识别变异的多效作用。为了确定 CAD 和 T2D 之间的新功能位点和多效关系，通过整合两个独立的大型和多中心 GWAS 以及 T2D（26,676 例病例和 132,532 例对照）和 CAD（60,801病例和 123,504 个对照）。应用 0.05 的 cFDR 显着性阈值，我们通过将多效性效应纳入条件分析框架，观察到 T2D 和 CAD 之间的多效性富集。我们为 T2D 鉴定了 79 个新的 CpG-SNP，为 CAD 鉴定了 61 个新的 CpG-SNP，以及两个性状的 18 个新的多效性位点。在这些新型CpG-SNPs中，有33个在全血中被注释为甲基化数量性状基因座（meQTL），其中10个同时表现出表达QTL（eQTL）、meQTL和代谢QTL（metaQTL）效应。据我们所知，我们对 CpG-SNP 进行了第一次靶向 cFDR 分析，我们的发现为 T2D 和 CAD 之间共享的生物学机制和重叠的遗传遗传性提供了新的见解。和代谢 QTL（metaQTL）同时作用。据我们所知，我们对 CpG-SNP 进行了第一次靶向 cFDR 分析，我们的发现为 T2D 和 CAD 之间共享的生物学机制和重叠的遗传遗传性提供了新的见解。和代谢 QTL（metaQTL）同时作用。据我们所知，我们对 CpG-SNP 进行了第一次靶向 cFDR 分析，我们的发现为 T2D 和 CAD 之间共享的生物学机制和重叠的遗传遗传性提供了新的见解。