| Chromatin marks identify critical cell types for fine mapping complex trait variants. | |
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MedLine Citation:
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PMID: 23263488 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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If trait-associated variants alter regulatory regions, then they should fall within chromatin marks in relevant cell types. However, it is unclear which of the many marks are most useful in defining cell types associated with disease and fine mapping variants. We hypothesized that informative marks are phenotypically cell type specific; that is, SNPs associated with the same trait likely overlap marks in the same cell type. We examined 15 chromatin marks and found that those highlighting active gene regulation were phenotypically cell type specific. Trimethylation of histone H3 at lysine 4 (H3K4me3) was the most phenotypically cell type specific (P < 1 × 10(-6)), driven by colocalization of variants and marks rather than gene proximity (P < 0.001). H3K4me3 peaks overlapped with 37 SNPs for plasma low-density lipoprotein concentration in the liver (P < 7 × 10(-5)), 31 SNPs for rheumatoid arthritis within CD4(+) regulatory T cells (P = 1 × 10(-4)), 67 SNPs for type 2 diabetes in pancreatic islet cells (P = 0.003) and the liver (P = 0.003), and 14 SNPs for neuropsychiatric disease in neuronal tissues (P = 0.007). We show how cell type-specific H3K4me3 peaks can inform the fine mapping of associated SNPs to identify causal variation. |
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Authors:
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Gosia Trynka; Cynthia Sandor; Buhm Han; Han Xu; Barbara E Stranger; X Shirley Liu; Soumya Raychaudhuri |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-12-23 |
Journal Detail:
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Title: Nature genetics Volume: 45 ISSN: 1546-1718 ISO Abbreviation: Nat. Genet. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-29 Completed Date: 2013-03-26 Revised Date: 2013-05-10 |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: United States |
Other Details:
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Languages: eng Pagination: 124-30 Citation Subset: IM |
Affiliation:
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Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Arthritis, Rheumatoid
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genetics* Chromatin / genetics* Databases, Genetic Diabetes Mellitus, Type 2 / genetics* Genetic Markers / genetics* Histones / genetics Humans Nervous System Diseases / genetics* Phenotype* Polymorphism, Single Nucleotide / genetics Software |
| Grant Support | |
ID/Acronym/Agency:
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K08AR055688/AR/NIAMS NIH HHS; R01 HG004069/HG/NHGRI NIH HHS; R01 HG004069/HG/NHGRI NIH HHS; U01HG0070033/HG/NHGRI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chromatin; 0/Genetic Markers; 0/Histones |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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