2021/02/05
论文
论文标题：Regulatory genomic circuitry of human disease loci by integrative epigenomics
作者：Carles A. Boix, Benjamin T. James, Yongjin P. Park, Wouter Meuleman, Manolis Kellis
期刊：Nature
发表时间：2021/02/03
数字识别码：10.1038/s41586-020-03145-z
摘要：Annotating the molecular basis of human disease remains an unsolved challenge, as 93% of disease loci are non-coding and gene-regulatory annotations are highly incomplete1,2,3. Here we present EpiMap, a compendium comprising 10,000 epigenomic maps across 800 samples, which we used to define chromatin states, high-resolution enhancers, enhancer modules, upstream regulators and downstream target genes. We used this resource to annotate 30,000 genetic loci that were associated with 540 traits4, predicting trait-relevant tissues, putative causal nucleotide variants in enriched tissue enhancers and candidate tissue-specific target genes for each. We partitioned multifactorial traits into tissue-specific contributing factors with distinct functional enrichments and disease comorbidity patterns, and revealed both single-factor monotropic and multifactor pleiotropic loci. Top-scoring loci frequently had multiple predicted driver variants, converging through multiple enhancers with a common target gene, multiple genes in common tissues, or multiple genes and multiple tissues, indicating extensive pleiotropy. Our results demonstrate the importance of dense, rich, high-resolution epigenomic annotations for the investigation of complex traits.
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所属学科：
基因组学
生物
非编码 DNA 延伸段在发育和基因调控中发挥着关键作用。21-2 月 3 日发表在《自然》（Nature）上的一项新研究称，来自美国麻省理工学院（MIT）的研究团队发表了迄今为止最全面的非编码基因组图谱，EpiMap（Epigenome Integration across Multiple Annotation Projects）。该图谱整合了之前几个大规模基因组图谱的数据，对 833 种组织和细胞类型的表观基因组标记进行了深入的注释，并显示出与 540 种特定性状相关的约 3 万个遗传变异的候选作用机制。该研究填补了缺失的基因组数据集，代表了迄今人类基因组最完整的“电路图”，对研究基因调控和人类疾病有重要意义。（Nature，MIT）
