The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY, 10029, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY, 10029, USA.
Commun Biol. 2022 Aug 20;5(1):849. doi: 10.1038/s42003-022-03820-z.
Phenome-wide association studies identified numerous loci associated with traits and diseases. To help interpret these associations, we constructed a phenome-wide network map of colocalized genes and phenotypes. We generated colocalized signals using the Genotype-Tissue Expression data and genome-wide association results in UK Biobank. We identified 9151 colocalized genes for 1411 phenotypes across 48 tissues. Then, we constructed bipartite networks using the colocalized signals in each tissue, and showed that the majority of links were observed in a single tissue. We applied the biLouvain clustering algorithm in each tissue-specific network to identify co-clusters of genes and phenotypes. We observed significant enrichments of these co-clusters with known biological and functional gene classes. Overall, the phenome-wide map provides links between genes, phenotypes and tissues, and can yield biological and clinical discoveries.
表型全基因组关联研究确定了许多与特征和疾病相关的基因座。为了帮助解释这些关联，我们构建了一个表型全基因组网络图谱，以显示共定位基因和表型。我们使用 UK Biobank 中的基因型组织表达数据和全基因组关联研究结果生成共定位信号。我们在 48 种组织中鉴定出 1411 种表型的 9151 个共定位基因。然后，我们使用每种组织中的共定位信号构建了二分网络，并表明大多数链接仅在单个组织中观察到。我们在每个组织特异性网络中应用了 biLouvain 聚类算法来识别基因和表型的共聚类。我们观察到这些共聚类与已知的生物学和功能基因类别显著富集。总体而言，表型全基因组图谱提供了基因、表型和组织之间的联系，并可能产生生物学和临床发现。
