Chromatin interactions and expression quantitative trait loci reveal genetic drivers of multimorbidities
Chromatin interactions and expression quantitative trait loci reveal genetic drivers of multimorbidities
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DOI：
10.1038/s41467-018-07692-y
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发表时间：
2018-12-05
影响因子：
16.6
通讯作者：
O'Sullivan, Justin M.
中科院分区：
文献类型：
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作者：
Fadason, Tayaza;Schierding, William;O'Sullivan, Justin M.
非传染性疾病的临床研究确定了多种疾病，这些疾病表明了一系列共同的诱发因素。尽管人类有类似的24 000个基因，但我们不了解导致多种非传染性疾病发展的遗传途径。在这里，我们创建了一个多形态特征图谱的基础上多效性的空间调控基因。利用染色质相互作用和表达数量性状基因座（eQTL）数据，我们分析了与1351种表型相关的20，782个变异（p < 5 x 10（-6）），以鉴定16，248个推定的空间eQTL-eGene对，它们参与了不同人类组织中的76，013个短距离和长距离调控相互作用（FDR < 0.05）。表型之间共享的空间eGenes的凸双聚类识别了名义上不同的表型相关SNP之间的复杂相互关系。我们的方法能够同时阐明与靶基因的变异相互作用，这些靶基因是多突变的驱动因素，以及那些有助于独特的表型相关特征的基因。
Clinical studies of non-communicable diseases identify multimorbidities that suggest a common set of predisposing factors. Despite the fact that humans have similar to 24,000 genes, we do not understand the genetic pathways that contribute to the development of multimorbid non-communicable disease. Here we create a multimorbidity atlas of traits based on pleiotropy of spatially regulated genes. Using chromatin interaction and expression Quantitative Trait Loci (eQTL) data, we analyse 20,782 variants (p < 5 x 10(-6)) associated with 1351 phenotypes to identify 16,248 putative spatial eQTL-eGene pairs that are involved in 76,013 short- and long-range regulatory interactions (FDR < 0.05) in different human tissues. Convex biclustering of spatial eGenes that are shared among phenotypes identifies complex interrelationships between nominally different phenotype-associated SNPs. Our approach enables the simultaneous elucidation of variant interactions with target genes that are drivers of multimorbidity, and those that contribute to unique phenotype associated characteristics.