Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study

Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study

Chlamydia trachomatis causes both trachoma and sexually transmitted infections. These diseases have similar pathology and potentially similar genetic predisposing factors. We aimed to identify polymorphisms and pathways associated with pathological sequelae of ocular Chlamydia trachomatis infections...

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Main Authors: Roberts, Chrissy h., Franklin, Christopher S., Makalo, Pateh, Joof, Hassan, Sarr, Isatou, Mahdi, Olaimatu S., Sillah, Ansumana, Bah, Momodou, Payne, Felicity, Jeffreys, Anna E., Bottomley, William, Natividad, Angels, Molina-Gonzalez, Sandra, Burr, Sarah E., Preston, Mark, Kwiatkowski, Dominic, Rockett, Kirk A., Clark, Taane G., Burton, Matthew J., Mabey, David C. W., Bailey, Robin, Barroso, Inês, Holland, Martin J.
Format: Online
Language:English
Published: Nature Publishing Group 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663496/
id pubmed-4663496
recordtype oai_dc
spelling pubmed-46634962015-12-03 Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study Roberts, Chrissy h. Franklin, Christopher S. Makalo, Pateh Joof, Hassan Sarr, Isatou Mahdi, Olaimatu S. Sillah, Ansumana Bah, Momodou Payne, Felicity Jeffreys, Anna E. Bottomley, William Natividad, Angels Molina-Gonzalez, Sandra Burr, Sarah E. Preston, Mark Kwiatkowski, Dominic Rockett, Kirk A. Clark, Taane G. Burton, Matthew J. Mabey, David C. W. Bailey, Robin Barroso, Inês Holland, Martin J. Article Chlamydia trachomatis causes both trachoma and sexually transmitted infections. These diseases have similar pathology and potentially similar genetic predisposing factors. We aimed to identify polymorphisms and pathways associated with pathological sequelae of ocular Chlamydia trachomatis infections in The Gambia. We report a discovery phase genome-wide association study (GWAS) of scarring trachoma (1090 cases, 1531 controls) that identified 27 SNPs with strong, but not genome-wide significant, association with disease (5 × 10−6 > P > 5 × 10−8). The most strongly associated SNP (rs111513399, P = 5.38 × 10−7) fell within a gene (PREX2) with homology to factors known to facilitate chlamydial entry to the host cell. Pathway analysis of GWAS data was significantly enriched for mitotic cell cycle processes (P = 0.001), the immune response (P = 0.00001) and for multiple cell surface receptor signalling pathways. New analyses of published transcriptome data sets from Gambia, Tanzania and Ethiopia also revealed that the same cell cycle and immune response pathways were enriched at the transcriptional level in various disease states. Although unconfirmed, the data suggest that genetic associations with chlamydial scarring disease may be focussed on processes relating to the immune response, the host cell cycle and cell surface receptor signalling. Nature Publishing Group 2015-11-30 /pmc/articles/PMC4663496/ /pubmed/26616738 http://dx.doi.org/10.1038/srep17447 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Roberts, Chrissy h.
Franklin, Christopher S.
Makalo, Pateh
Joof, Hassan
Sarr, Isatou
Mahdi, Olaimatu S.
Sillah, Ansumana
Bah, Momodou
Payne, Felicity
Jeffreys, Anna E.
Bottomley, William
Natividad, Angels
Molina-Gonzalez, Sandra
Burr, Sarah E.
Preston, Mark
Kwiatkowski, Dominic
Rockett, Kirk A.
Clark, Taane G.
Burton, Matthew J.
Mabey, David C. W.
Bailey, Robin
Barroso, Inês
Holland, Martin J.
spellingShingle Roberts, Chrissy h.
Franklin, Christopher S.
Makalo, Pateh
Joof, Hassan
Sarr, Isatou
Mahdi, Olaimatu S.
Sillah, Ansumana
Bah, Momodou
Payne, Felicity
Jeffreys, Anna E.
Bottomley, William
Natividad, Angels
Molina-Gonzalez, Sandra
Burr, Sarah E.
Preston, Mark
Kwiatkowski, Dominic
Rockett, Kirk A.
Clark, Taane G.
Burton, Matthew J.
Mabey, David C. W.
Bailey, Robin
Barroso, Inês
Holland, Martin J.
Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study
author_facet Roberts, Chrissy h.
Franklin, Christopher S.
Makalo, Pateh
Joof, Hassan
Sarr, Isatou
Mahdi, Olaimatu S.
Sillah, Ansumana
Bah, Momodou
Payne, Felicity
Jeffreys, Anna E.
Bottomley, William
Natividad, Angels
Molina-Gonzalez, Sandra
Burr, Sarah E.
Preston, Mark
Kwiatkowski, Dominic
Rockett, Kirk A.
Clark, Taane G.
Burton, Matthew J.
Mabey, David C. W.
Bailey, Robin
Barroso, Inês
Holland, Martin J.
author_sort Roberts, Chrissy h.
title Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study
title_short Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study
title_full Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study
title_fullStr Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study
title_full_unstemmed Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study
title_sort conjunctival fibrosis and the innate barriers to chlamydia trachomatis intracellular infection: a genome wide association study
description Chlamydia trachomatis causes both trachoma and sexually transmitted infections. These diseases have similar pathology and potentially similar genetic predisposing factors. We aimed to identify polymorphisms and pathways associated with pathological sequelae of ocular Chlamydia trachomatis infections in The Gambia. We report a discovery phase genome-wide association study (GWAS) of scarring trachoma (1090 cases, 1531 controls) that identified 27 SNPs with strong, but not genome-wide significant, association with disease (5 × 10−6 > P > 5 × 10−8). The most strongly associated SNP (rs111513399, P = 5.38 × 10−7) fell within a gene (PREX2) with homology to factors known to facilitate chlamydial entry to the host cell. Pathway analysis of GWAS data was significantly enriched for mitotic cell cycle processes (P = 0.001), the immune response (P = 0.00001) and for multiple cell surface receptor signalling pathways. New analyses of published transcriptome data sets from Gambia, Tanzania and Ethiopia also revealed that the same cell cycle and immune response pathways were enriched at the transcriptional level in various disease states. Although unconfirmed, the data suggest that genetic associations with chlamydial scarring disease may be focussed on processes relating to the immune response, the host cell cycle and cell surface receptor signalling.
publisher Nature Publishing Group
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663496/
_version_ 1613507521901756416

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