Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis

Abstract The involvement of the immune system, particularly the role of T-cells, in sarcoidosis is unclear. The existence of higher CD4+ T-cells and increased CD4/CD8 ratio may indicate a pathogenic role of T-cells in the disease. In this study, we quantified the contribution of T-cells associated v...

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Autores principales:	Natalia V. Rivera, Michael Hagemann-Jensen, Manuel A. R. Ferreira, Susanna Kullberg, Anders Eklund, Nicholas G. Martin, Leonid Padyukov, Johan Grunewald
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e196b0950aa04c5383295d23737710a7
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spelling	oai:doaj.org-article:e196b0950aa04c5383295d23737710a72021-12-02T15:06:19ZCommon variants of T-cells contribute differently to phenotypic variation in sarcoidosis10.1038/s41598-017-05754-72045-2322https://doaj.org/article/e196b0950aa04c5383295d23737710a72017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05754-7https://doaj.org/toc/2045-2322Abstract The involvement of the immune system, particularly the role of T-cells, in sarcoidosis is unclear. The existence of higher CD4+ T-cells and increased CD4/CD8 ratio may indicate a pathogenic role of T-cells in the disease. In this study, we quantified the contribution of T-cells associated variants and of CD4/CD8 ratio in sarcoidosis phenotypes, Löfgren’s syndrome (LS) and non- Löfgren’s syndrome (non-LS). We employed a polygenic-based approach using genome-wide association studies results on relative levels of T-cells in healthy individuals to measure the genetic contribution of T-cells in sarcoidosis entities. Results revealed that the genetic architecture of LS is highly influenced by genetic variants associated with CD8+ T-cells and CD4/CD8 ratio, explaining up to 7.94% and 6.49% of LS variation, respectively; whereas, the genetic architecture of non-LS is minimally influenced by T-cells, explaining a phenotypic variation of <1%. Moreover, pleiotropy assessment between T-cells and LS/non-LS associated-variants led to the discovery of highly scored pathway maps that shared common factors related to antigen presentation and T-cell regulatory mechanisms. Differences in significant polygenic scores, presence of pleiotropy, and distinct genetic factors provide further insights on how genetic variants and genes associated with relative levels of T-cell subtypes contribute differently to sarcoidosis phenotypes.Natalia V. RiveraMichael Hagemann-JensenManuel A. R. FerreiraSusanna KullbergAnders EklundNicholas G. MartinLeonid PadyukovJohan GrunewaldNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Natalia V. Rivera Michael Hagemann-Jensen Manuel A. R. Ferreira Susanna Kullberg Anders Eklund Nicholas G. Martin Leonid Padyukov Johan Grunewald Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis
description	Abstract The involvement of the immune system, particularly the role of T-cells, in sarcoidosis is unclear. The existence of higher CD4+ T-cells and increased CD4/CD8 ratio may indicate a pathogenic role of T-cells in the disease. In this study, we quantified the contribution of T-cells associated variants and of CD4/CD8 ratio in sarcoidosis phenotypes, Löfgren’s syndrome (LS) and non- Löfgren’s syndrome (non-LS). We employed a polygenic-based approach using genome-wide association studies results on relative levels of T-cells in healthy individuals to measure the genetic contribution of T-cells in sarcoidosis entities. Results revealed that the genetic architecture of LS is highly influenced by genetic variants associated with CD8+ T-cells and CD4/CD8 ratio, explaining up to 7.94% and 6.49% of LS variation, respectively; whereas, the genetic architecture of non-LS is minimally influenced by T-cells, explaining a phenotypic variation of <1%. Moreover, pleiotropy assessment between T-cells and LS/non-LS associated-variants led to the discovery of highly scored pathway maps that shared common factors related to antigen presentation and T-cell regulatory mechanisms. Differences in significant polygenic scores, presence of pleiotropy, and distinct genetic factors provide further insights on how genetic variants and genes associated with relative levels of T-cell subtypes contribute differently to sarcoidosis phenotypes.
format	article
author	Natalia V. Rivera Michael Hagemann-Jensen Manuel A. R. Ferreira Susanna Kullberg Anders Eklund Nicholas G. Martin Leonid Padyukov Johan Grunewald
author_facet	Natalia V. Rivera Michael Hagemann-Jensen Manuel A. R. Ferreira Susanna Kullberg Anders Eklund Nicholas G. Martin Leonid Padyukov Johan Grunewald
author_sort	Natalia V. Rivera
title	Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis
title_short	Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis
title_full	Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis
title_fullStr	Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis
title_full_unstemmed	Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis
title_sort	common variants of t-cells contribute differently to phenotypic variation in sarcoidosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e196b0950aa04c5383295d23737710a7
work_keys_str_mv	AT nataliavrivera commonvariantsoftcellscontributedifferentlytophenotypicvariationinsarcoidosis AT michaelhagemannjensen commonvariantsoftcellscontributedifferentlytophenotypicvariationinsarcoidosis AT manuelarferreira commonvariantsoftcellscontributedifferentlytophenotypicvariationinsarcoidosis AT susannakullberg commonvariantsoftcellscontributedifferentlytophenotypicvariationinsarcoidosis AT anderseklund commonvariantsoftcellscontributedifferentlytophenotypicvariationinsarcoidosis AT nicholasgmartin commonvariantsoftcellscontributedifferentlytophenotypicvariationinsarcoidosis AT leonidpadyukov commonvariantsoftcellscontributedifferentlytophenotypicvariationinsarcoidosis AT johangrunewald commonvariantsoftcellscontributedifferentlytophenotypicvariationinsarcoidosis
_version_	1718388549322014720

Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis

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