{"doi":"10.1016/j.ajhg.2017.03.002","title":"Functional Architectures of Local and Distal Regulation of Gene Expression in Multiple Human Tissues","abstract":null,"journal":"The American Journal of Human Genetics","year":2017,"id":593548,"datarank":0.7117398192544876,"base_score":4.74493212836325,"endowment":4.74493212836325,"self_citation_contribution":0.7117398192544876,"citation_network_contribution":0.0,"self_endowment_contribution":0.7117398192544876,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":114,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":8,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":3039,"name":"Hilary K. Finucane","orcid":"0000-0003-3864-9828","position":1,"is_corresponding":false},{"id":6113,"name":"Alexander Gusev","orcid":"0000-0002-7980-4620","position":2,"is_corresponding":false},{"id":532550,"name":"Gaurav Bhatia","orcid":null,"position":3,"is_corresponding":false},{"id":558848,"name":"Steven Gazal","orcid":"0000-0001-5714-7597","position":4,"is_corresponding":false},{"id":388279,"name":"Luke O’Connor","orcid":"0000-0003-1938-2064","position":5,"is_corresponding":false},{"id":1519123,"name":"Brendan Bulik-Sullivan","orcid":null,"position":6,"is_corresponding":false},{"id":103619,"name":"Fred A. Wright","orcid":"0000-0002-8238-6626","position":7,"is_corresponding":false},{"id":213,"name":"Patrick F. Sullivan","orcid":"0000-0002-6619-873X","position":8,"is_corresponding":false},{"id":104455,"name":"Benjamin M. Neale","orcid":"0000-0003-1513-6077","position":9,"is_corresponding":false},{"id":22002,"name":"Alkes L. Price","orcid":"0000-0002-2971-7975","position":10,"is_corresponding":false},{"id":16087,"name":"Xuanyao Liu","orcid":"0000-0002-5955-6738","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Functional Architectures of Local and Distal Regulation of Gene Expression in Multiple Human Tissues","abstract":"Genetic variants that modulate gene expression levels play an important role in the etiology of human diseases and complex traits. Although large-scale eQTL mapping studies routinely identify many local eQTLs, the molecular mechanisms by which genetic variants regulate expression remain unclear, particularly for distal eQTLs, which these studies are not well powered to detect. Here, we leveraged all variants (not just those that pass stringent significance thresholds) to analyze the functional architecture of local and distal regulation of gene expression in 15 human tissues by employing an extension of stratified LD-score regression that produces robust results in simulations. The top enriched functional categories in local regulation of peripheral-blood gene expression included coding regions (11.41×), conserved regions (4.67×), and four histone marks (p < 5 × 10<sup>-5</sup> for all enrichments); local enrichments were similar across the 15 tissues. We also observed substantial enrichments for distal regulation of peripheral-blood gene expression: coding regions (4.47×), conserved regions (4.51×), and two histone marks (p < 3 × 10<sup>-7</sup> for all enrichments). Analyses of the genetic correlation of gene expression across tissues confirmed that local regulation of gene expression is largely shared across tissues but that distal regulation is highly tissue specific. Our results elucidate the functional components of the genetic architecture of local and distal regulation of gene expression.","is_dataset_classified":null,"base_score":4.74493212836325,"endowment":4.74493212836325,"datacite_reuse_total":8,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28343628","pmcid":"PMC5384099","openalex_id":"https://openalex.org/W2602141149","authors":[],"funders":[{"funder_name":"NIH","grant_id":"R01 MH107649","title":null},{"funder_name":"US National Institute of Mental Health","grant_id":"U01 MH109528","title":null}],"total_grants":2,"fwci":5.4731,"citation_percentile":0.96887543,"influential_citations":0,"citation_trend":[{"year":2016,"count":1},{"year":2017,"count":8},{"year":2018,"count":21},{"year":2019,"count":10},{"year":2020,"count":14},{"year":2021,"count":10},{"year":2022,"count":16},{"year":2023,"count":6},{"year":2024,"count":9},{"year":2025,"count":12},{"year":2026,"count":7}],"oa_status":"bronze","license":"https://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"http://www.cell.com/article/S0002929717301052/pdf","host_type":"journal"},{"url":"http://www.cell.com/article/S0002929717301052/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0002929717301052?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0002929717301052?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.ajhg.2017.03.002","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28343628","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5384099","host_type":"repository"}],"fields_of_study":["RNA Research and Splicing","Genomics and Chromatin Dynamics","Gene expression and cancer classification"],"mesh_terms":["Anxiety","Computer Simulation","Depression","Gene Expression Regulation","Humans","Organ Specificity","Regression Analysis","Twins","Linkage Disequilibrium","Quantitative Trait Loci"],"keywords":["Gene","Gene expression","Expression (computer science)","Biology","Cell biology","Regulation of gene expression","Computational biology","Genetics","Computer science","Programming language","Gene expression regulation","Heritability","Functional Annotation","Eqtls"],"sdg_mappings":[],"linked_datasets":[{"doi":"10.6084/m9.figshare.12858506.v1","title":"Additional file 1 of GBAT: a gene-based association test for robust detection of trans-gene regulation","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.12858506","title":"Additional file 1 of GBAT: a gene-based association test for robust detection of trans-gene regulation","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.12858512.v1","title":"Additional file 3 of GBAT: a gene-based association test for robust detection of trans-gene regulation","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.12858512","title":"Additional file 3 of GBAT: a gene-based association test for robust detection of trans-gene regulation","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19642045.v1","title":"Additional file 1 of A Bayesian framework to integrate multi-level genome-scale data for Autism risk gene prioritization","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19642045","title":"Additional file 1 of A Bayesian framework to integrate multi-level genome-scale data for Autism risk gene prioritization","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.12858509","title":"Additional file 2 of GBAT: a gene-based association test for robust detection of trans-gene regulation","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.12858509.v1","title":"Additional file 2 of GBAT: a gene-based association test for robust detection of trans-gene regulation","publisher":"figshare","resource_type":"Dataset"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T11:25:26.286242Z","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,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}