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| PMID |
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| TITLE |
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| Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis. |
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| ABSTRACT |
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| 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. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2016/09/28 |
| accepted |
2017/06/02 |
| entrez |
2017/07/19 06:00 |
| pubmed |
2017/07/19 06:00 |
| medline |
2017/07/19 06:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Rivera NV |
|
Rivera |
Natalia V |
NV |
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Center for Molecular Medicine, Karolinska Institutet, SE-171 76, Stockholm, Sweden. natalia.rivera@ki.se. |
| Hagemann-Jensen M |
|
Hagemann-Jensen |
Michael |
M |
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Center for Molecular Medicine, Karolinska Institutet, SE-171 76, Stockholm, Sweden. |
| Ferreira MAR |
|
Ferreira |
Manuel A R |
MAR |
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QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Queensland, 4029, Australia. |
| Kullberg S |
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Kullberg |
Susanna |
S |
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Department of Medicine, Respiratory Unit, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden. |
| Eklund A |
|
Eklund |
Anders |
A |
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Department of Medicine, Respiratory Unit, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
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QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Queensland, 4029, Australia. |
| Padyukov L |
|
Padyukov |
Leonid |
L |
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Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden. |
| Grunewald J |
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Grunewald |
Johan |
J |
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Center for Molecular Medicine, Karolinska Institutet, SE-171 76, Stockholm, Sweden. johan.grunewad@ki.se. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: 7 |
| ISSUE: 1 |
| TITLE: Scientific reports |
| ISOABBREVIATION: Sci Rep |
| YEAR: 2017 |
| MONTH: Jul |
| DAY: 17 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 2045-2322 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Sci Rep |
| COUNTRY: England |
| ISSNLINKING: 2045-2322 |
| NLMUNIQUEID: 101563288 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| REFTYPE |
REFSOURCE |
REFPMID |
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