基因表达
计算生物学
关节炎
基因
基因表达调控
表达式(计算机科学)
生物
生物信息学
遗传学
计算机科学
免疫学
程序设计语言
作者
Feng Jiang,Shou-Ye Hu,Wen Tian,Naining Wang,Ning Yang,Shanshan Dong,Hui-Miao Song,Dajin Zhang,Huafang Gao,Chen Wang,Hao Wu,Changyi He,Dong-Li Zhu,Xiao-Feng Chen,Yan Guo,Zhi Yang,Tie‐Lin Yang
标识
DOI:10.1038/s41467-024-45652-x
摘要
Abstract The synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition. We identify 4765 independent primary and 616 secondary cis -expression quantitative trait loci ( cis -eQTLs) in the synovium and find that the eQTLs with multiple independent signals have stronger effects and heritability than single independent eQTLs. Integration of genome-wide association studies (GWASs) and eQTLs identifies 84 arthritis related genes, revealing 38 novel genes which have not been reported by previous studies using eQTL data from the GTEx project or immune cells. We further develop a method called eQTac to identify variants that could affect gene expression by affecting chromatin accessibility and identify 1517 regions with potential regulatory function of chromatin accessibility. Altogether, our study provides a comprehensive synovium multi-omics resource for arthritic diseases and gains new insights into the regulation of gene expression.
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