Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
28717140
TITLE
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 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.
DATE PUBLISHED
2017 Jul 17
HISTORY
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
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Rivera NV Rivera Natalia V NV Center for Molecular Medicine, Karolinska Institutet, SE-171 76, Stockholm, Sweden. natalia.rivera@ki.se.
Hagemann-Jensen M Hagemann-Jensen Michael M Center for Molecular Medicine, Karolinska Institutet, SE-171 76, Stockholm, Sweden.
Ferreira MAR Ferreira Manuel A R MAR QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Queensland, 4029, Australia.
Kullberg S Kullberg Susanna S Department of Medicine, Respiratory Unit, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
Eklund A Eklund Anders A Department of Medicine, Respiratory Unit, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Queensland, 4029, Australia.
Padyukov L Padyukov Leonid L Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
Grunewald J Grunewald Johan J Center for Molecular Medicine, Karolinska Institutet, SE-171 76, Stockholm, Sweden. johan.grunewad@ki.se.
INVESTIGATORS
JOURNAL
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
MEDLINE JOURNAL
MEDLINETA: Sci Rep
COUNTRY: England
ISSNLINKING: 2045-2322
NLMUNIQUEID: 101563288
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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