High-density genetic mapping identifies new susceptibility variants in sarcoidosis phenotypes and shows genomic-driven phenotypic differences
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F16%3A33156193" target="_blank" >RIV/61989592:15110/16:33156193 - isvavai.cz</a>
Result on the web
<a href="http://www.atsjournals.org/doi/full/10.1164/rccm.201507-1372OC" target="_blank" >http://www.atsjournals.org/doi/full/10.1164/rccm.201507-1372OC</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1164/rccm.201507-1372OC" target="_blank" >10.1164/rccm.201507-1372OC</a>
Alternative languages
Result language
angličtina
Original language name
High-density genetic mapping identifies new susceptibility variants in sarcoidosis phenotypes and shows genomic-driven phenotypic differences
Original language description
Rationale: Sarcoidosis is a multisystem disease of unknown cause(s). Löfgren's syndrome (LS) is a characteristic subgroup of sarcoidosis that is associated with a good prognosis in sarcoidosis. However, little is known about its genetic architecture or its broader phenotype non-LS sarcoidosis. Objective: To address the genetic architecture of sarcoidosis phenotypes, LS and non-LS. Methods: An association study in a Swedish Caucasian cohort of 384 LS, 664 non-LS and 2,086 controls, totaling 3,134 subjects employing a fine-mapping genotyping platform was conducted. Replication was performed in four independent cohorts, three of white European decent, Germany (N = 4,975), The Netherlands (N = 613), and Czech Republic (N =521), and one of black African descent, USA (N = 1,657), totaling altogether 7,766 subjects. Main Results: A total of 727 LS-associated variants expanding throughout the extended major histocompatibility complex (MHC) region and 68 non-LS-associated variants located in the MHC class II region were identified and confirmed. Noteworthy, a shared overlap between LS and non-LS defined by 17 variants located in the MHC class II region was found. Outside the MHC region, two LS-associated loci, in ADCY3 and between CSMD1 and MCPH1 were observed and replicated. Conclusions: Comprehensive and integrative analyses of genetics, transcription, and pathway modeling on LS and non-LS indicates that these sarcoidosis phenotypes have different genetic-susceptibility, genomic distributions, and cellular activities, suggesting distinct molecular mechanisms in pathways related to immune-response with a common region.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FC - Pneumology
OECD FORD branch
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Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
American Journal of Respiratory and Critical Care Medicine
ISSN
1073-449X
e-ISSN
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Volume of the periodical
193
Issue of the periodical within the volume
9
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
1008-1022
UT code for WoS article
000375118200017
EID of the result in the Scopus database
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