Document Detail


Chromatin marks identify critical cell types for fine mapping complex trait variants.
MedLine Citation:
PMID:  23263488     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Gosia Trynka; Cynthia Sandor; Buhm Han; Han Xu; Barbara E Stranger; X Shirley Liu; Soumya Raychaudhuri
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-23
Journal Detail:
Title:  Nature genetics     Volume:  45     ISSN:  1546-1718     ISO Abbreviation:  Nat. Genet.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-29     Completed Date:  2013-03-26     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  124-30     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Arthritis, Rheumatoid / 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:
K08 AR055688/AR/NIAMS NIH HHS; K08AR055688/AR/NIAMS NIH HHS; R01 HG004069/HG/NHGRI NIH HHS; R01 HG004069/HG/NHGRI NIH HHS; U01 HG007033/HG/NHGRI NIH HHS; U01HG0070033/HG/NHGRI NIH HHS
Chemical
Reg. No./Substance:
0/Chromatin; 0/Genetic Markers; 0/Histones
Comments/Corrections

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