دورية أكاديمية
أعرض في EDS

Regulatory genomic circuitry of human disease loci by integrative epigenomics.

التفاصيل البيبلوغرافية
العنوان: Regulatory genomic circuitry of human disease loci by integrative epigenomics.
المؤلفون: Boix CA; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA, USA., James BT; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Park YP; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Meuleman W; Altius Institute for Biomedical Sciences, Seattle, WA, USA., Kellis M; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA. manoli@mit.edu.; Broad Institute of MIT and Harvard, Cambridge, MA, USA. manoli@mit.edu.
المصدر: Nature [Nature] 2021 Feb; Vol. 590 (7845), pp. 300-307. Date of Electronic Publication: 2021 Feb 03.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
أسماء مطبوعة: Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
مواضيع طبية MeSH: Epigenomics*, Disease/*genetics , Epigenesis, Genetic/*genetics , Gene Regulatory Networks/*genetics , Genetic Loci/*genetics, Chromatin/genetics ; Enhancer Elements, Genetic/genetics ; Female ; Genome-Wide Association Study ; Humans ; Male ; Multifactorial Inheritance/genetics ; Organ Specificity/genetics ; Reproducibility of Results
مستخلص: 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 1-3 . 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 traits 4 , 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.
التعليقات: Comment in: Cardiovasc Res. 2021 May 25;117(6):e73-e75. (PMID: 33914859)
Comment in: Signal Transduct Target Ther. 2021 May 8;6(1):179. (PMID: 33966052)
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معلومات مُعتمدة: HG008155 United States NH NIH HHS; U41 HG007234 United States HG NHGRI NIH HHS; MH109978 United States NH NIH HHS; MH119509 United States NH NIH HHS; U24 HG009446 United States HG NHGRI NIH HHS; GM087237 United States NH NIH HHS; HG007234 United States NH NIH HHS; R01 MH109978 United States MH NIMH NIH HHS; U01 MH119509 United States MH NIMH NIH HHS; R01 AG058002 United States AG NIA NIH HHS; R01 HG008155 United States HG NHGRI NIH HHS; R35 HG011317 United States HG NHGRI NIH HHS; R01 GM113708 United States GM NIGMS NIH HHS; U01 HG007610 United States HG NHGRI NIH HHS; HG009446 United States NH NIH HHS; HG009088 United States NH NIH HHS; T32 GM087237 United States GM NIGMS NIH HHS; AG058002 United States NH NIH HHS; HG007610 United States NH NIH HHS; GM113708 United States NH NIH HHS; U01 HG009088 United States HG NHGRI NIH HHS
المشرفين على المادة: 0 (Chromatin)
تواريخ الأحداث: Date Created: 20210204 Date Completed: 20210309 Latest Revision: 20230129
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7875769
DOI: 10.1038/s41586-020-03145-z
PMID: 33536621
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4687
DOI:10.1038/s41586-020-03145-z