Imperial College London
Alternate

Dr Antonio J Berlanga-Taylor

Faculty of Medicine, School of Public Health

Honorary Senior Research Fellow
 
 
 
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Contact

 

a.berlanga

 
 
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Location

 

47 Praed StreetSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Elangovan:2014:10.1038/jhg.2014.3,
author = {Elangovan, RI and Disanto, G and Berlanga-Taylor, AJ and Ramagopalan, SV and Handunnetthi, L},
doi = {10.1038/jhg.2014.3},
journal = {J Hum Genet},
pages = {211--215},
title = {Regulatory genomic regions active in immune cell types explain a large proportion of the genetic risk of multiple sclerosis.},
url = {http://dx.doi.org/10.1038/jhg.2014.3},
volume = {59},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - There is little understanding of how genetic variants discovered in recent genome-wide association studies are involved in the pathogenesis of multiple sclerosis (MS). We aimed to investigate which chromatin states and cell types explain genetic risk in MS. We used genotype data from 1854 MS patients and 5164 controls produced by the International Multiple Sclerosis Genetics Consortium and Wellcome Trust Case Control Consortium. We estimated the proportion of phenotypic variance between cases and controls explained by cell-specific chromatin state and DNase I hypersensitivity sites (DHSs) using the Genome-wide Complex Trait Analysis software. A large proportion of variance was explained by single-nucleotide polymorphisms (SNPs) in strong enhancer (SE) elements of immortalized B lymphocytes (5.39%). Three independent SNPs located within SE showed suggestive evidence of association with MS: rs12928822 (odds ratio (OR)=0.81, 95% confidence interval (CI)=0.73-0.89, P=2.48E-05), rs727263 (OR=0.75, 95% CI=0.66-0.85, P=3.26E-06) and rs4674923 (OR=0.85, 95% CI=0.79-0.92, P=1.63E-05). Genetic variants located within DHSs of CD19+ B cells explained the greatest proportion of variance. Genetic variants influencing the risk of MS are located within regulatory elements active in immune cells. This study also identifies a number of immune cell types likely to be involved in the causal cascade and that carry important implications for future studies of therapeutic design.
AU  - Elangovan,RI
AU  - Disanto,G
AU  - Berlanga-Taylor,AJ
AU  - Ramagopalan,SV
AU  - Handunnetthi,L
DO  - 10.1038/jhg.2014.3
EP  - 215
PY  - 2014///
SP  - 211
TI  - Regulatory genomic regions active in immune cell types explain a large proportion of the genetic risk of multiple sclerosis.
T2  - J Hum Genet
UR  - http://dx.doi.org/10.1038/jhg.2014.3
UR  - https://www.ncbi.nlm.nih.gov/pubmed/24522295
VL  - 59
ER  -
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