Biomedical Informatics Training Program, Stanford University, Stanford, CA.
Inflammation & Immunology, Pfizer Inc., Cambridge, MA.
Inflamm Bowel Dis. 2018 Feb 15;24(3):471-481. doi: 10.1093/ibd/izx087.
Monogenic diseases have been shown to contribute to complex disease risk and may hold new insights into the underlying biological mechanism of Inflammatory Bowel Disease (IBD).
We analyzed Mendelian disease associations with IBD using over 55 million patients from the Optum's deidentified electronic health records dataset database. Using the significant Mendelian diseases, we performed pathway enrichment analysis and constructed a model using gene expression datasets to differentiate Crohn's disease (CD), ulcerative colitis (UC), and healthy patient samples.
We found 50 Mendelian diseases were significantly associated with IBD, with 40 being significantly associated with both CD and UC. Our results for CD replicated those from previous studies. Pathways that were enriched consisted of mainly immune and metabolic processes with a focus on tolerance and oxidative stress. Our 3-way classifier for UC, CD, and healthy samples yielded an accuracy of 72%.
Mendelian diseases that are significantly associated with IBD may reveal novel insights into the genetic architecture of IBD.
单基因疾病已被证明与复杂疾病风险有关，并且可能为炎症性肠病（IBD）的潜在生物学机制提供新的见解。
我们使用来自 Optum 去识别电子健康记录数据库的超过 5500 万患者，分析孟德尔疾病与 IBD 的关联。使用显著的孟德尔疾病，我们进行了途径富集分析，并使用基因表达数据集构建了一个模型，以区分克罗恩病（CD）、溃疡性结肠炎（UC）和健康患者样本。
我们发现 50 种孟德尔疾病与 IBD 显著相关，其中 40 种与 CD 和 UC 均显著相关。我们对 CD 的研究结果与之前的研究结果一致。富集的途径主要包括免疫和代谢过程，重点是耐受和氧化应激。我们的 UC、CD 和健康样本的三分类器的准确率为 72%。
与 IBD 显著相关的孟德尔疾病可能揭示 IBD 遗传结构的新见解。
