{"doi":"10.1038/s41586-020-03145-z","title":"Regulatory genomic circuitry of human disease loci by integrative epigenomics","abstract":"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 incomplete<sup>1-3</sup>. 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 traits<sup>4</sup>, 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.","journal":"Nature","year":2021,"id":3901,"datarank":7.691458202679694,"base_score":6.0844994130751715,"endowment":6.0844994130751715,"self_citation_contribution":0.9126749119612758,"citation_network_contribution":6.778783290718419,"self_endowment_contribution":0.9126749119612758,"citer_contribution":6.778783290718419,"corpus_percentile":74.77624084621644,"corpus_rank":311,"citation_count":458,"citer_count":189,"citers_with_citation_signal":189,"citers_with_endowment":189,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.8927,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-02-03","algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":39697,"name":"Benjamin T. James","orcid":"0000-0002-6228-055X","position":1,"is_corresponding":false},{"id":7736,"name":"Yongjin P. Park","orcid":"0000-0001-8915-2876","position":2,"is_corresponding":false},{"id":36155,"name":"Wouter Meuleman","orcid":"0000-0002-1196-5401","position":3,"is_corresponding":false},{"id":14693,"name":"Sharon L. R. Kardia","orcid":"0000-0002-9853-3379","position":4,"is_corresponding":false},{"id":4960,"name":"Carles B. Adsera","orcid":"0000-0001-9212-856X","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}